Effects of Pallidal Deep Brain Stimulation Location on Motor Impairment in Parkinson's Disease
• diagnosis of idiopathic PD
• have undergone neurosurgery to implant deep brain stimulators in the globus pallidus (GP DBS) or subthalamic nucleus (STN)
• Existing 7T brain imagery
• history of musculoskeletal disorders that significantly affect movement of the upper or lower limbs
• other significant neurological disorder
• history of dementia or cognitive impairment as found with UBACC (or MacCAT-CR)
• post-operative complications or adverse effects
Precision Promise Platform Trial for Metastatic Pancreatic Cancer
A Multi-center Trial to Evaluate Multiple Regimens in Metastatic Pancreatic Cancer
- Age ≥ 18 years.
- Histologically or cytologically confirmed metastatic pancreatic ductal adenocarcinoma (PDAC) and eligible for treatment in the first line or second line settings.
- Acceptable histologies include adenosquamous carcinoma, mucinous adenocarcinoma, hepatoid carcinoma, medullary carcinoma, signet ring cell carcinoma, undifferentiated
carcinoma, and undifferentiated carcinoma with osteoclast-like-cells, and adenocarcinoma. Pancreatic neuroendocrine tumors (PNET) are excluded.
o Note: prior adjuvant or neoadjuvant chemotherapy is permitted if the last dose was > 12 months prior to the diagnosis of metastatic disease.
- Radiographically measurable disease of at least one site by computed tomography (CT) scan (or magnetic resonance imaging, if allergic to CT contrast media) as defined by
Response Evaluation Criteria In Solid Tumors (RECIST) 1.1. Imaging results must be obtained within the 21-day window, prior to randomization.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
- Adequate organ function (lab results must be obtained within the 21-day window prior to randomization)
- Absolute neutrophil count ≥ 1500/mm^3.
- Hemoglobin ≥ the lower limit of normal (LLN) or 9g/dL.
- Platelets ≥ 100,000/mm^3.
- Serum creatinine ≤ 1.0 x upper limit normal (ULN), or calculated creatinine clearance ≥ 50 mL/min (Cockcroft Gault).
- Albumin ≥ 3.0 g/dL.
- Aspartate aminotransferase (AST) serum glutamic oxaloacetic transaminase (SGOT) and/or alanine aminotransferase (ALT) serum glutamic pyruvic transaminase (SGPT) ≤ 2.5 x ULN (up to ≤ 5 x ULN in presence of liver metastasis).
- Total bilirubin ≤ 1.5 x ULN.
- INR ≤ 1.5 x ULN (up to ≤ 2 x ULN for subjects on anticoagulation therapy).
- Subjects must be willing to provide protocol-mandated tissue and blood samples for diagnostic and research purposes as a condition of enrollment into the trial.
- Able to swallow pills, capsules or tablets.
- Able to adhere to study visit schedule and other protocol requirements.
- Females of childbearing potential [defined as a sexually mature woman who (1) has not undergone hysterectomy (the surgical removal of the uterus) or bilateral oophorectomy
(the surgical removal of both ovaries) or (2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time during the
preceding 24 consecutive months)] must:
- Have a negative serum or urine pregnancy test (?-human chorionic gonadotropin [?-hCG]) as verified by the study doctor within 14 days prior to randomization;
- Commit to complete abstinence from heterosexual contact or agree to use medical doctor-approved contraception throughout the study without interruption while receiving study treatment and for at least 6 months following last dose of study treatment.
- Males must practice complete abstinence or agree to use a condom (even if he has undergone a successful vasectomy) during sexual contact with a pregnant female or a
female of childbearing potential while participating in the study, during dose interruptions and for at least 6 months following last dose of study treatment.
- HIV-infected subjects on effective anti-retroviral therapy are eligible if the most recent viral load test performed within six months of screening (based on medical chart review) is negative. If this is not the case, an HIV viral load test should be performed at screening and be negative (i.e., undetectable).
- HBV-infected subjects are eligible if the most recent viral load test performed within six months of screening (based on medical chart review) is negative. If this is not the case, an HBV viral load test should be performed at screening and be negative (i.e., undetectable).
- Subjects with a history of hepatitis C virus (HCV) infection must have been treated and cured. Subjects with HCV infection who are currently on treatment are eligible if
the most recent viral load test performed within six months of screening (based on medical chart review) is negative. If this is not the case, an HCV viral load test should be performed at screening and be negative (i.e., undetectable).
- Subjects with a history of brain metastases are eligible provided they show evidence of stable lesions (and no new lesions) with no evidence of tumor progression for at
least 4 weeks after CNS-directed treatment, as ascertained by clinical examination and brain imaging (MRI or CT) during the screening period. In addition, any neurological
symptoms that developed either as a result of the brain metastases or their treatment, must have returned to baseline or resolved. Any steroids administered as part of this therapy must be completed > 7 days prior to the first dose of trial therapy.
- No known leptomeningeal disease.
- Subjects with a prior or concurrent malignancy whose natural history does not have the potential to interfere with the safety or efficacy assessment of the investigational
regimen are eligible. Subjects receiving any active therapy for a concurrent secondary malignancy are excluded.
- Subjects with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac
function using New York Heart Association Functional Classification. To be eligible for this trial, subjects should be Class 2 or better. Class 2 is defined as slight limitation of physical activity, in which ordinary physical activity leads to fatigue, palpitation, or dyspnea; the person is comfortable at rest.
- Understands the nature of the study and has agreed to participate by voluntarily signing the IRB approved informed consent.
- Received any therapy within 21 days (or 5 half-lives, whichever is shorter,) prior to randomization.
- Has had major surgery within 14 days prior to enrollment.
- History of known allergy or hypersensitivity to any of the study treatments or any of their excipients or contraindication to any of the study treatments as outlined in the
local prescribing information (e.g., United States Prescribing Information [USPI]).
- Pre-existing peripheral neuropathy > Grade 1, as defined by CTCAE V 4.03.
- Known active tuberculosis infection.
- Serious, non-healing wound, ulcer, bone fracture, or abscess.
- The inability to swallow pills, capsules or tablets.
- Subjects who received a combination of two investigational agents as part of first-line therapy (novel + novel) are excluded. Subjects who received one investigational agent or one investigational agent combined with an FDA approved
chemotherapy regimen in first line will be allowed to be enrolled in Precision PromiseSM for second line therapy.
- Receiving any active therapy for a concurrent secondary malignancy. Subjects with a prior or concurrent malignancy whose natural history does not have the potential to
interfere with the safety or efficacy assessment of the investigational regimen are eligible.
- History of interstitial lung disease, history of slowly progressive dyspnea and unproductive cough, sarcoidosis, silicosis, idiopathic pulmonary fibrosis, pulmonary
hypersensitivity pneumonitis or multiple allergies.
- QTc > 450 msec if male and QTc > 470 msec if female.
- Uncontrolled or severe cardiac disease (history of unstable angina, myocardial infarction, coronary stenting, or bypass surgery within the prior 6 months), symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia
[including atrial flutter/fibrillation].
- Subjects with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac
function using New York Heart Association Functional Classification. Subjects worse than Class 2 are excluded. Class 2 is defined as slight limitation of physical
activity, in which ordinary physical activity leads to fatigue, palpitation, or dyspnea; the person is comfortable at rest.
- Active, uncontrolled infections (bacterial, viral, or fungal infection(s)) requiring systemic therapy, defined as ongoing signs/symptoms related to the infection without improvement despite appropriate antibiotics, antiviral therapy, and/or other treatment (i.e., subjects must be afebrile for > 48 hours off antibiotics).
- Active, known or suspected autoimmune disease, including systemic lupus erythematosus, Hashimotos thyroiditis, scleroderma, polyarteritis nodosa or autoimmune hepatitis.
o Subjects with type I diabetes mellitus, hypothyroidism requiring only hormone replacement, skin disorders (such as vitiligo, psoriasis or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are eligible to participate.
- Receiving immunosuppressive or myelosuppressive medications that would, in the opinion of the Investigator, increase the risk of serious neutropenic complications. Subjects receiving replacement therapy of 10 mg of prednisone (or the equivalent hydrocortisone dose) per day are eligible.
- Receipt of live vaccines within 30 days prior to the first dose of study treatment or while on active treatment within the trial. (examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, chicken pox, yellow fever, rabies, BCG, and typhoid (oral) vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are permitted. However, intranasal influenza
vaccines (e.g., Flu-Mist®) are live attenuated vaccines and are not permitted).
- Any significant medical condition, laboratory abnormality or psychiatric illness that would limit the subject's ability to comply with study requirements.
- Subjects that discontinued previous treatment for pancreatic adenocarcinoma due to a treatment-related Grade 3 toxicity.
- For toxicity discontinuations < Grade 3, AE(s) must resolve to Grade 1 or baseline in order to be considered eligible for this trial.
- Subjects that have received allogenic bone marrow or solid organ transplants are excluded.
Cluster Headache Treatment with Rimegepant-Open Label Pilot Study (Rimegepant)
Cluster Headache Treatment with Rimegepant
- Having a diagnosis of recurrent cluster headaches, as described by ICHD-3 (International Classification of Headache Disorders-3):
- Severe or very severe unilateral orbital, supraorbital and/or temporal pain lasting 15-180 minutes, when untreated.
- Headache is accompanied by at least one of the following:
- Ipsilateral conjunctival injection and/or lacrimation;
- Ipsilateral nasal congestion and/or rhinorrhea;
- Ipsilateral eyelid edema;
- Ipsilateral forehead and facial sweating;
- Ipsilateral miosis and/or ptosis;
- A sense of restlessness or agitation.
- Headache attacks occur at a frequency between every other day and 8 per day.
- Headaches are not attributed to another disorder.
- Subjects able to distinguish cluster headache attacks from other headache disorders, such as migraine.
- Subjects on prophylactic headache medicines other than verapamil will be permitted to remain on these with possible headache-prophylactic effects if the dose is stable for
at least 2 months (onabotulinumtoxinA injections stable for 6 months) prior to the screening visit and the dose is not expected to change during the course of the study.
- Prior MR (magnetic resonance) imaging of head (CT if MRI contraindicated) performed after the onset of headaches.
- Subjects agree to refrain from starting a new prophylactic cluster headache medicine, including steroids and nerve blocks, during the course of the study.
- Subjects are required to have a cluster headache attack fre-quency ranging from one attack every other day to eight attacks per day, with at least four total attacks during the one-week prospective baseline period. Additionally, episodic cluster headache patients are required to have a history of cluster head-ache period lasting at least 6 weeks.
- Subjects with a history of an adverse reaction to CGRP (calcitonin gene-related peptide) antibodies or another CGRP antagonist (gepant).
- Subjects with episodic cluster who are felt to be toward the end of their cluster cycle (estimated to be within the last 4 weeks).
- Pregnancy (negative serum pregnancy testing at enrollment and use of contraception considered to be effective).
- Subjects with a history of uncontrolled, unstable, or recently diagnosed cardiovascular disease, such as ischemic heart disease, coronary artery vasospasm, and cerebral ischemia. Subjects with myocardial infarction (MI), percutaneous coronary intervention (PCI), coronary artery bypass graft (CABG), stroke, or transient ischemic attack (TIA) in the 6 months prior to screening.
- Subjects with other pain syndromes, psychiatric conditions, dementia or significant neurological disorders that, in the investigator's opinion might interfere with study assessments.
- Use of peripheral nerve blocks (e.g., occipital, supraorbital, auriculotemporal, and/or sphenopalatine ganglion nerve blocks) one month prior to enrollment.
- Use of opioids or barbiturates more than 5 days per month.
- Use of other small molecule CGRP antagonist (gepant) 1 month prior to enrollment or during duration of study.
- Use of verapamil during the study.
- Use of CGRP monoclonal antibodies 3 months prior to enrollment or during duration of study.
- Subjects with a secondary cluster headache related to an underlying structural etiology identified by imaging (CT or MRI).
Eligibility last updated 3/8/23 to match clinicaltrials.gov. Questions regarding updates should be directed to the study team contact.
Echocardiographic Findings Associated With Rapid Weight Loss in Collegiate Wrestlers
Echocardiographic Findings of Collegiate Wrestlers With Rapid Weight Loss
- Wrestlers on roster from Rochester Community and Technical College.
- ≥ 18 years of age.
- Any athlete with a known cardiac condition will be excluded.
Eligibility last updated 8/23/22. Questions regarding updates should be directed to the study team contact.
Development of an EEG Diagnostic for Alzheimer’s Disease: A Feasibility Study (DEEGDAD)
A Study to Develop an EEG Diagnostic for Alzheimer’s Disease
- Unimpaired APOE e4/4 homozygotes age 65-75 and APOE e3/4 heterozygotes age 75-85 for the preclinical AD subset and age, sex, and education matched APOE e4 noncarriers for the unaffected controls.
- Biomarker confirmation for preclinical diagnosis will be utilized to the extent possible (a subset of 130 members of our cohort have undergone amyloid-PET resulting in approximately 45 who are amyloid positive).
Exclusion Criteria:
- Previous stroke.
- Severe head injury.
- Craniotomy.
- Any other potentially confounding neurologic illness (typically anything that causes structural brain damage).
- Psychoactive medication use will not be an absolute exclusionary criterion in patients with moderate to severe dementia but patients who are relatively drug-free will be prioritized to the extent they are available within the study period.
- Psychoactive drug use will be exclusionary in the prospectively obtained clinical patients.
An Open Label, Multi-Center, Phase 3 Efficacy Study of Sub-Q Abatacept (Orencia) in Preventing Extension of Oligoarticular Juvenile Idiopathic Arthritis JIA (Limit-JIA) (LIMIT JIA)
Preventing Extension of Oligoarticular Juvenile Idiopathic Arthritis JIA (Limit-JIA)
1. Age ≥ 2 years old and ≤16.5 years old
2. Clinical diagnosis of JIA by a pediatric rheumatologist within the past 6 months
3. Arthritis affecting ≤4 joints between disease onset and randomization
4. Enrollment in the CARRA Registry
5. Participants of childbearing potential must agree to remain abstinent or agree to use
an effective and medically acceptable form of birth control from the time of written
or verbal assent to at least 66 days after taking the last dose of study drug.
6. Weight ≥50 kg (Canadian Sites only) ¹ Enrollment is defined as having signed consent
to participate in the Limit-JIA study.
The presence of any of the following will exclude a study participant from inclusion in the
study:
1. 1. Systemic JIA as defined by 2004 ILAR criteria1
2. Sacroiliitis (clinical or radiographic)
3. Inflammatory bowel disease (IBD)
4. History of psoriasis or currently active psoriasis
5. History of uveitis or currently active uveitis
6. Prior treatment with systemic medication(s) for JIA (e.g. one or more of the
following: DMARD or biologic medication)
7. Current or previous (within 30 days of enrollment) treatment with systemic
glucocorticoids (A short course of oral prednisone [≤ 14 days] is allowed)
8. History of active or chronic liver disease
9. Chronic or acute renal disorder
10. AST (SGOT), ALT (SGPT) or BUN >2 x ULN (upper limit of normal) or creatinine >1.5
mg/dL or any other laboratory abnormality considered by the examining physician to be
clinically significant within 2 months of the randomization visit
11. Presence of any medical or psychological condition or laboratory result which would
make the participant, in the opinion of the investigator, unsuitable for the study
12. Participation in another concurrent clinical interventional study within 30 days of
randomization
13. Known positive human immunodeficiency virus (HIV)
14. Received a live virus vaccine within 1 month of the baseline visit
15. Current or prior positive Purified Protein Derivative (PPD) test or Quantiferon Gold
TB
16. Pregnant, breast feeding, or planned breast feeding during the study duration
17. Planned transfer to non-participating pediatric rheumatology center or adult
rheumatologist in the next 12 months
18. Active malignancy of any type or history of malignancy
19. Chronic or active infection or any major episode of infection requiring
hospitalization or treatment with intravenous (IV) antibiotics within 30 days or oral
antibiotics within 14 days prior to screening
20. Primary language other than English or Spanish
21. Positive for Hepatitis B surface antigen or core antibody
22. <10 Kg in weight
23. If a potential subject has symptoms consistent with COVID-19 and/or known COVID-19
exposure at screening, it is recommended that the site follow CDC guidance regarding
testing and quarantine requirements. The subject can be re-screened when there is no
longer concern for active infection. A subject with a positive COVID -19 test may be
re-screened.
Multicenter Phenotype-Genotype Analysis of Vascular Anomalies and Related Syndromes
A Study to Analyze Phenotype-Genotype Vascular Anomalies
- Individual of any age from infant to adult.
- Able and willing to provide consent/assent
- Diagnosed with a vascular anomaly or discrepancy of growth.
Subjects will continue to be followed for this study until any of the following events occur:
- Withdrawal of consent.
- Documentation of dissent after enrollment.
- Refusal to re-consent after turning 18 years old.
- Lost to follow up.
- Physician discretion.
Eligibility last updated 8/1/22. Questions regarding updates should be directed to the study team contact.
Intestinal Permeability in Patients with Active Inflammatory Bowel Disease: Towards Development of a Non-invasive, Inexpensive Test to Detect Intestinal Inflammation
Developing a Non-invasive Test to Detect Intestinal Inflammation in Active Inflammatory Bowel Disease
Recruitment of 40 IBD patients (20 with active IBD, 20 with IBD in remission, with equal numbers of Crohn’s (CD) and ulcerative colitis (UC)) with thoroughly evaluated IBD (endoscopy, histopathology, or CT enterography):
- Active disease as defined by SES-CD (PMID: 15472670) > 6 (> 4 if ileal only), AND active symptoms of CD (CDAI score > 220) or full Mayo score for UC ≥ 2 with an endoscopy score of ≥2 (PMID: 31272578) within the past 4-6 weeks. 9,10,11,12,13
- Remission as defined by SES-CD 0-2 and CDAI score ≤150, or full Mayo score for UC 0-2 with endoscopy score < 2.9,10,11,12,13.
- Ability to give informed consent.
Healthy Adults
- ≥ 18 years age.
- No underlying medical illnesses that could serve as confounders with the objectives of the study.
Recruitment of 40 IBD patients (20 with active IBD, 20 with IBD in remission, with equal numbers of Crohn’s (CD) and ulcerative colitis (UC)) with thoroughly evaluated IBD (endoscopy, histopathology, or CT enterography):
- Less than 18 years of age.
- Prior history gastrointestinal surgeries including IPAA, ileostomy and colostomy.
- Use of NSAIDs or aspirin and unable or unwilling to stop taking two weeks prior to permeability test.
- Use of osmotic laxatives and unable to unwilling to stop taking one week prior to permeability test.
- Use of oral corticosteroids and unable or unwilling to stop use of oral corticosteroids within the previous two weeks and for the duration of the study.
- Multiple dietary restrictions or unable or unwilling to alter dietary protein or dietary fiber for the permeability testing.
- Unwilling or unable to stop ingestion of alcohol and artificial sweeteners such as Splenda™ (sucralose), Nutrasweet™ (aspartame), sorbitol, xylitol, lactulose, or mannitol 2 days before and during the permeability testing days, e.g. foods to be avoided are sugarless gums or mints and diet beverages.
- Bowel preparation for colonoscopy must be completed more than 48 hours prior to completion of permeability test. If intestinal biopsies were performed, 7 days must pass prior to permeability testing.
- Pregnancy or plan to become pregnant during the study time frame.
- Vulnerable adult.
Healthy Adults
- Less than 18 years of age.
Eligibility last updated 9/2/22. Questions regarding updates should be directed to the study team contact.
Harnessing the Power of Technology to Transform Delirium Severity Measurement in the ICU
Power of Technology to Transform Delirium Severity Measurement in the ICU
Aim 1-3 Patient Participants
- Age ≥ 50 years old;
- Estimated length of stay ≥ 24 hours in ICU; and
- Are not admitted for acute alcohol intoxication, drug (prescribed or illicit) overdose or withdrawal.
Aim 3 Nurse Clinician Participants
- Age ≥ 18 years old;
- Employed by Mayo Clinic;
- Assigned to care for study patient for > 4 hours.
Aim 3 Care Partner Participants
- Age ≥ 18 years old;
- Proxy decision maker for patient participant;
- Willing to complete survey (verbal consent).
Aim 1-3 Patient Participants
- Admitted for acute alcohol intoxication, drug (prescribed or illicit) overdose or withdrawal;
- Admitted for acute neuronal injury;
- Unable to communicate with research team due to sensory deficits (aphasic, blind, deaf); or
- Language (does not speak English).
Aim 3 Nurse Clinician Participants
- Not assigned to study patient.
Aim 3 Care Partner Participants
- Did not visit patient in ICU during study period;
- Already listed above in previous protocol version, was not copied/mentioned here.
Eligibility last updated 12/1/22. Questions regarding updates should be directed to the study team contact.
Assessing Movement Disorder Patients P1A4
• Diagnosis or suspected diagnosis of Parkinson's disease, Essential Tremor, or Dystonia
• Aged: 10+
• History of dementia
• Patients with post-operative complications or adverse effects that affect patient safety or confound the experiment will be excluded from further study.
• Pregnant women
• Lactating women
AFFIRM-LITE: A Phase 2 Randomized, Placebo-Controlled Study of Alleviation by Fisetin of Frailty, Inflammation, and Related Measures in Older Adults (AFFIRM-LITE)
Alleviation by Fisetin of Frailty, Inflammation, and Related Measures in Older Women
Inclusion Criteria
- Age ≥ 70 years
Exclusion Criteria
- Unable or unwilling to give informed consent
- Pregnant
- Body weight >150 kg or body mass index (BMI) > 50
- QTc>450 msec
- Total bilirubin >2X upper limit of normal
- Inability to tolerate oral medication
- Abnormality in any of the screening laboratory studies (see below)
- Human immunodeficiency virus infection
- Known active hepatitis B or C infection
- Invasive fungal or viral infection
- Known hypersensitivity or allergy to fisetin
- Uncontrolled pleural/pericardial effusions or ascites
- New/active invasive cancer except non-melanoma skin cancers
- Subjects taking medications that are sensitive to substrates or substrates with a
narrow therapeutic range for CYP3A4, CYP2C8, CYP2C9, or CYP2D6 or strong inhibitors or
inducers of CYP3A4 (e.g. cyclosporine, tacrolimus or sirolimus). If antifungals are
absolutely necessary from an infectious disease perspective, then they will be allowed
only if the levels are therapeutic.
- Strong inhibitors of CYP3A4. See Appendices 1-3.
- Tyrosine kinase inhibitor therapy
- Known hypersensitivity or allergy to fisetin
- Subjects on quinolone antibiotic therapy for treatment or for prevention of infections
within 10 days.
- Subjects taking H2-antagonists and unwilling to discontinue therapy for 1 week before
and 2 weeks following enrollment.
- Subjects taking potentially senolytic agents within the last year: Fisetin, Quercetin,
Luteolin, Dasatinib, Piperlongumine, or Navitoclax
- Subjects currently taking drugs that induce cellular senescence: alkylating agents,
anthracyclines, platins, other chemotherapy
- Subjects taking the following antimicrobial agents: Aminoglycosides, Azole antifungals
(fluconazole, miconazole, voriconazole, itraconazole), Macrolides
(clarithromycin,erythromycin), Antivirals (nelfinavir, indinavir, saquinavir,
ritonavir, elbasvir/grazoprevir), Rifampin
- Subjects taking proton pump inhibitors who are unable or unwilling to reduce or hold
therapy 2 days prior to and during the 2-day Fisetin dosing
- Subjects taking the following other drugs if they cannot be held for at least 2 days
before and during administration of Fisetin: digoxin, lithium, all statins,
repaglidine, bosentan, gemfibrozil, olmesartan, enalapril, valsartan, methotrexate,
corticosteroids, , eluxadoline, eltrombopag, nitroglycerin, pioglitazone, glyburide,
enzalutamide, ezetimibe, colchicine, imatinib, cyclosporine, tacolimus, sirolimus,
carbamazepine, flecainide, phenytoin, phenobarbital, rifampicin, theophylline,
celecoxib, desipramine, thioridazine, venlafaxine, tizanidine, atomoxetine,
voriconazole, citalopram, diazepam, escitalopram, propranolol, clozapine,
cyclobenzaprine, mexiletine, olanzapine, ondansetron, riluzole
- In order to ensure vitamin D sufficiency, we will also exclude subjects with serum
25-hydroxyvitamin D levels of < 20 ng/ml.
- Presence of any condition that the Investigator believes would put the subject at risk
or would preclude the patient from successfully completing all aspects of the trial.
Behavioral Modification
•Participants will be educated about the risk of excessive
caffeine usage. Participants will be encouraged to reduce use by 50% prior to and during
the 2-day drug dosing period. Due to drug-drug interaction, subjects may not clear the
caffeine from their system properly/as usual.
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Eligibility last updated 9/20/22. Questions regarding updates should be directed to the study team contact.
LIBRETTO-432: A Placebo-controlled, Double-Blinded Randomized Phase 3 Study of Adjuvant Selpercatinib following Definitive Locoregional Treatment in Participants with Stage IB-IIIA RET fusion-Positive NSCLC (LIBRETTO-432)
A Study of Selpercatinib Following Definitive Locoregional Treatment in Participants with Non-small Cell Lung Cancer
A Placebo-Controlled Efficacy in iNPH Shunting (PENS) Trial (PENS)
Efficacy in iNPH Shunting (PENS) Trial
1. Age ≥ 60 years; and
2. Diagnosis of iNPH and recommendation for shunt surgery based on the Investigator's
clinical judgement based on criteria and testing as described in the iNPH Guidelines;
3. Evans Ratio ≥ 0.30; and
4. One positive supplementary test to include either large volume Lumbar Puncture or
extended CSF drainage per institutional standards; and
5. History or evidence of gait impairment (such as decreased step height or length,
decreased speed, retropulsion as described in the iNPH Guidelines) duration ≥ 6
months; and
6. Participant has the sensory motor skills, communication skills and understanding to
comply with the testing and reporting required in the PENS trial; and
7. Participant is able to give written informed consent.
1. Unable to walk 10 meters with or without an assistive device; or
2. Baseline fastest gait velocity (out of three gait trials) >1 m/sec prior to drainage
trial and fastest gait velocity improvement is < 30% with or without an assistive
device; or
3. Unable to return to the study center for follow up evaluation and shunt programming;
or
4. Participant is not medically cleared for shunt surgery per local standards; or
5. Secondary NPH. (Prior encephalitis, meningitis, subarachnoid hemorrhage, traumatic
brain injury (including concussion) within two years or with brain injury or skull
fracture on baseline imaging, brain abscess, brain tumor, obstructive hydrocephalus
(including acquired aqueductal stenosis and carcinomatous meningitis); or
6. Prior or existing shunts, endoscopic third ventriculostomy, or any previous surgical
intervention for hydrocephalus; or
7. Previous intracranial neurosurgical procedure; or
8. Symptomatic cerebral or cerebellar infarction occurring within 6 months from screening
(asymptomatic lacunar infarctions are permitted); or
9. Diagnosis of Parkinsonian syndrome that, in the investigator's judgment, will
complicate the outcome evaluation; or
10. Diagnosis of schizophrenia or any psychiatric diagnosis (including depression) that,
in the investigator's judgment, will complicate the outcome evaluation (such as
neuroleptic treatment for schizophrenia); or
11. Diagnosis of dementia disorder where the investigator considers cognition deficit
limits participation in the study; or
12. Conditions impairing gait that are considered to be unrelated to hydrocephalus, such
as hemiparesis, spasticity, cerebellar ataxia or musculoskeletal and joint disease,
which will interfere with gait assessment or the potential for gait improvement.
13. Individuals with contraindication to MRI (e.g., implanted electric and electronic
devices, aneurysm clip(s), any metallic fragment or foreign body, coronary and
peripheral artery stents, cardiac pacemaker, known claustrophobia, or known/possible
pregnancy or breast-feeding) will be excluded according to institutional guidelines.
A Pilot Study to Investigate Non-Invasive Positive Pressure Ventilation on Oxygen Saturations without Supplemental Oxygen at Altitude
Non-Invasive Positive Pressure Ventilation on Oxygen Saturations without Supplemental Oxygen at Altitude
- Healthy male or female participants.
- Between the ages of 18 and 89.
- Must have had experience as a pilot or passenger in an unpressurized general aviation aircraft at altitudes above 8,000 feet and have not experienced any serious adverse effects from this experience (such as serious vertigo, loss of consciousness, any cardiac or respiratory dysfunction, or any other illness requiring medical treatment).
- Participants need to be able to complete cognitive tests.
- Must be fluent in English.
- Patients < 18 years of age or > 89 years of age.
- Pregnant women.
- Unable to read and speak English.
- History of Cardiac disease, Pulmonary disease, Cerebrovascular disease, Neurological disease, Vertigo, or Syncope.
- Any documented incidences of Serious Adverse effects from General Aviation.
Safety and Effectiveness of Balloon-Expandable Bioprosthetic SAPIEN X4 Transcatheter Heart Valve
ALLIANCE: Safety and Effectiveness of the SAPIEN X4 Transcatheter Heart Valve
1. Severe, calcific AS
2. Native aortic annulus size suitable for SAPIEN X4 THV
3. NYHA functional class ≥ II
4. The subject has been informed of the nature of the study, agrees to its provisions and has provided written informed consent.
1. Anatomical characteristics that would preclude safe femoral placement of the introducer sheath or safe passage of the delivery system
2. Aortic valve is unicuspid, bicuspid or non-calcified
3. Pre-existing mechanical or bioprosthetic valve in any position
4. Severe aortic regurgitation (> 3+)
5. Severe mitral regurgitation (> 3+) or ≥ moderate mitral stenosis
6. Need for mitral, tricuspid or pulmonic valve intervention within the next 12 months
7. Left ventricular ejection fraction < 20%
8. Cardiac imaging evidence of intracardiac mass, thrombus or vegetation
9. Left ventricular outflow tract calcification that would increase the risk of annular rupture or significant PVL after THV implantation
10. Increased risk of coronary artery obstruction after THV implantation
11. Myocardial infarction within 30 days prior to the study procedure
12. Hypertrophic cardiomyopathy with subvalvular obstruction
13. Subjects with planned concomitant ablation for atrial fibrillation
14. Complex coronary artery disease (CAD) that cannot be optimally treated by percutaneous coronary intervention (PCI)
15. Any surgical or transcatheter procedure within 30 days prior to the study procedure (unless part of planned strategy for treatment of CAD). Implantation of a permanent
pacemaker or implantable cardioverter defibrillator (ICD) is not considered an exclusion.
16. Any planned surgical or transcatheter intervention to be performed within 30 days following the study procedure (unless part of planned strategy for treatment of CAD)
17. Endocarditis within 180 days prior to the study procedure
18. Stroke, transient ischemic attack or neurological signs and symptoms attributed to carotid or vertebrobasilar disease within 90 days prior to the study procedure
19. Hemodynamic or respiratory instability requiring inotropic or mechanical support within 30 days prior to the study procedure
20. Renal insufficiency and/or renal replacement therapy
21. . Leukopenia (white blood cells [WBC] < 3000 cells/µmL), anemia (hemoglobin [Hgb] < 9 g/dL), thrombocytopenia (platelets < 50,000 cells/µmL)
22. Inability to tolerate or condition precluding treatment with antithrombotic therapy
23. Hypercoagulable state or other condition that increases risk of thrombosis
24. Absolute contraindications or allergy to iodinated contrast that cannot be adequately treated with premedication
25. Subject refuses blood products
26. BMI > 50 kg/m^2
27. Estimated life expectancy < 24 months
28. Female who is pregnant or lactating
29. Active SARS-CoV-2 infection or previously diagnosed with COVID-19 with sequelae that could confound endpoint assessments
30. Participating in another investigational drug or device study that has not reached its primary endpoint
31. Subject considered to be part of a vulnerable population
Eligibility last updated 8/24/23. Questions regarding updates should be directed to the study team contact.
The Clinical Outcome of Cardiac Resynchronization Therapy
A Study of Long-Term Outcomes of Cardiac Resynchronization Therapy Recipients with Congestive Heart Failure
- Patients who receive CRT-P or CRT-D device at Mayo Clinic since 1998
A Phase 3, Multicenter, Randomized, Controlled, Open-Label, Assessor-Blinded Study to Evaluate the Efficacy and Safety of Inhaled Isoflurane Delivered via the Sedaconda ACD-S Compared to Intravenous Propofol for Sedation of Mechanically Ventilated Intensive Care Unit Adult Patients (INSPiRE-ICU1)
Efficacy and Safety of Inhaled Isoflurane Delivered Via the Sedaconda ACD-S Compared to Intravenous Propofol for Sedation of Mechanically Ventilated Intensive Care Unit Adult Patients (INSPiRE-ICU1)
- Adults ≥ 18 years of age;
- Patients who are anticipated to require >12 hours of invasive mechanical ventilation and continuous sedation in the ICU; and
- Receipt of continuous sedation due to clinical need for sedation to RASS < 0.
- Need for RASS -5.
- Sedation for invasive mechanical ventilation immediately prior to Baseline for > 72 hours (patients who have been extubated for at least 24 hours and subsequently re-intubated will have sedation for invasive mechanical ventilation starting from when they were re-intubated);
- Severe neurological condition that causes the patient to lack ability to participate in the study (i.e., unable to be assessed for RASS and Critical Care Pain Observation Tool), including, but not restricted to, patients with acute stroke, severe head trauma, meningitis, suspected of having elevated intracranial pressure (ICP), or the need for ICP monitoring;
- Ventilator tidal volume 1000 mL at Baseline;
- Need for extracorporeal membrane oxygenation, extracorporeal carbon dioxide removal, high frequency oscillation ventilation, or high frequency percussive ventilation at Screening;
- Comfort care only (end of life care);
Contraindication to propofol or isoflurane, including:
- Known or suspected personal or family history of malignant hyperthermia (MH) or high risk for MH or acute drug-induced muscle injury (e.g., muscular dystrophies);
- Severe hemodynamic compromise, defined as the need for norepinephrine ≥ 0.3 mcg/kg/min (or equivalent vasopressor dose) to maintain blood pressure within acceptable range, assumed to be mean arterial pressure ≥ 65 mmHg unless prescribed clinically; or
- Allergy to isoflurane or propofol, or have propofol infusion syndrome.
- History of ventricular tachycardia/Long QT Syndrome;
- Requirement of intravenous (IV) benzodiazepine or barbiturate administration for seizures or dependencies, including alcohol withdrawal;
- Neuromuscular disease that impairs spontaneous ventilation (eg, C5 or higher spinal cord injury, amyotrophic lateral sclerosis, etc);
- Concurrent enrollment in another study that, in the Investigator’s opinion, would impact the patient’s safety or assessments of this study;
- Participation in other study involving investigational drug(s) or devices(s) within 30 days prior to Randomization;
- Previous randomization or receipt of treatment in this study or in SED004;
- Anticipated requirement of treatment with continuous infusion of a neuromuscular blocking agent for > 4 hours;
- Female patients who are pregnant or breast-feeding;
- Imperative need for continuous active humidification through mechanical ventilation circuit;
- Attending physician’s refusal to include the patient; or
- Inability to obtain informed consent.
Note: Other protocol defined Inclusion/Exclusion Criteria may apply.
Eligibility last updated 12/15/23. Questions regarding updates should be directed to the study team contact.
Mixed Reality Technology Integration Into Clinical Care
Integration of Mixed Reality Technology Into Clinical Care
- Age 18 to 100 years old.
- Able to consent.
- Pregnant women, fetuses or neonaters.
- Prisoners.
- Children.
- Adults lacking capacity to consent.
Eligibility last updated 4/22/22. Questions regarding updates should be directed to the study team contact.
Home-based Pulmonary Rehabilitation and Health Coaching in Bronchiectasis
Home-based Pulmonary Rehabilitation and Health Coaching to Treat Bronchiectasis
- Adult patients, ≥ 18 years old.
- Having a diagnosis of non-cystic fibrosis bronchiectasis (primary inclusion criteria) ,confirmed by records, that are symptomatic.
- Ability to communicate in English.
- Inability to walk (orthopedic/neurologic/cardiac limitation causing immobility).
- Cognitive impairment or inability to understand and follow instructions.
- Traditional PR completed within 3 months of study recruitment.
- Hospice or end-of-life care at the time of screening.
- Acute exacerbation at the time of screening.
Eligibility last updated 5/2/22. Questions regarding updates should be directed to the study team contact.
Quantitative Analysis of Short-Term Follow-Up CT Scan in Patients Undergoing Bronchoscopic Lung Volume Reduction (BLVR) with Endobronchial Valves
Postprocedural CT Scan in Patients Undergoing Bronchoscopic Lung Volume Reduction with Endobronchial Valves to Determine Benefit or Adverse Effects
- Age ≥ 18 years.
- Subjects must have undergone bronchoscopic lung volume reduction with endobronchial valve(s) placement for treatment of emphysema at Mayo Clinic-Rochester within timeframe of 3/01/2022 to 2/28/2023.
- Subjects must consent to undergoing CT scan of the chest prior to hospital discharge.
- Previous endobronchial valve placement (i.e., undergoing secondary procedure to have additional valves placed or valves upsized).
- Presence of large post-procedure pneumothorax, as defined by > 2 cm of air present between lung margin and chest wall measured at level of the hilum, identified prior to study CT acquisition.
Eligibility last updated 3/1/22. Questions regarding updates should be directed to the study team contact.
MC220301 Targeted Prevention of Post-Partum-Related Breast Cancer
Low Dose Aspirin for the Prevention of Postpartum Related Breast Cancer
Inclusion Criteria
•Pre-Registration:
- Age ≥ 18 years and ≤ 45 years of age.
- Presence of lesion suspicious for benign breast disease on mammography and planned breast biopsy.
- Had a live birth ≤ 5 years prior to pre-registration.
- Pre-menopausal.
- Provide written informed consent.
- Ability to complete questionnaire(s) by themselves or with assistance.
- Willingness to provide mandatory blood and urine specimens for correlative research.
- Willingness to provide mandatory tissue specimens for correlative research.
Inclusion Criteria
•Registration:
- Age ≥ 18 years and ≤ 45 years of age.
- Histological confirmation of benign breast disease (i.e., no evidence of DCIS or invasive cancer).
- Registration must be completed ≤ 30 days after pre-registration biopsy performed for this study.
- Hemoglobin ≥ 9.0 g/dL (obtained ≤ 30 days prior to registration).
- Platelet count ≥ 100,000/mm^3 (obtained ≤ 30 days prior to registration.
- Serum creatinine ≤ 2.0 mg/dl (obtained ≤ days prior to registration).
- Negative pregnancy test done ≤ 7 days prior to registration.
- Willing to use contraception while on treatment.
- Provide written informed consent.
- Ability to complete questionnaire(s) by themselves or with assistance.
- Willingness to provide mandatory blood and urine specimens for correlative research.
- Willingness to provide mandatory tissue specimens for correlative research.
- Willing to return to enrolling institution for follow-up.
Exclusion Criteria
•Pre-Registration:
- History of breast cancer including ductal breast carcinoma in situ (DCIS).
- Received systemic treatment for any other cancer at any time.
- Currently taking aspirin or other non-steroidal anti-inflammatory drugs (NSAIDS) (no doses within ≤ 5 days prior to pre-registration and no more than four doses within ≤ 30 days prior to pre-registration).
- Currently taking other agents for the prevention of breast cancer.
- Currently taking anticoagulants.
- Contraindication for aspirin use.
Exclusion Criteria
•Registration:
- No research tissue collected during pre-registration biopsy performed for this study.
- Currently taking aspirin or other non-steroidal anti-inflammatory drugs (NSAIDs).
- NOTE: no doses within ≤ 5 days prior to registration and no more than four doses within ≤ 30 days prior to registration.
- Co-morbid illnesses/conditions which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens.
- Any contraindication to aspirin use including but not limited to:
- Bleeding disorders (e.g., hemophilia);
- Stomach or intestinal bleeding ≤ 6 months prior to registration;
- Known allergy to other non-steroidal anti-inflammatory drugs (NSAIDs).
- Currently taking anticoagulants.
- Any malignancy requiring systemic therapy.
- Currently pregnant or planning to become pregnant in the next 90 days.
- Post-menopausal:
- Prior bilateral surgical oophorectomy; or
- No menses for > 1 year with estradiol levels within postmenopausal range, according to institutional standard.
Eligibility last updated 1/3/23. Questions regarding updates should be directed to the study team contact.
HeadStart4: Newly Diagnosed Children (<10 y/o) With Medulloblastoma and Other CNS Embryonal Tumors Clinical and Molecular Risk-Tailored Intensive and Compressed Induction Chemotherapy Followed by Consolidation With Randomization to Either Single Cycle or to Three Tandem Cycles of Marrow-Ablative Chemotherapy With Autologous Hematopoietic Progenitor Cell Rescue (NEXT)
HeadStart4: Newly Diagnosed Children (<10 y/o) With Medulloblastoma and Other CNS Embryonal Tumors
- Children ≥ 10 years old at the time of definitive confirmatory eligibile histologic or cytological diagnosis of eligible CNS tumor within the brain or spinal cord.
- Children who have not previously received either irridation or chemotherapy (except corticosteriods).
CNS Embryonal Tumors:
- All children less than 120 months (10 years) of age, irrespective of clinical stage, with a diagnosis of any of the following CNS embryonal tumors are eligible, whether located primarily in the brain or spinal cord: pineoblastoma, pineal anlage tumor, CNS neuroblastoma, CNS ganglioneuroblastoma, embryonal tumor with multi-layered rosettes (ETMR, including embryonal tumor with abundant neuropil and true rosettes (ETANTR), ependymoblastoma and ETMR not otherwise specified), medulloepithelioma, CNS embryonal tumor with rhabdoid features (INI1 intact) and CNS embryonal tumor, not otherwise specified.
- Children < 10 years of age.
- The exclusive focus is on medulloblastoma and other CNS embryonal tumors of the brain or spinal cord as follows:
Medulloblastoma:
- Posterior fossa classic, desmoplastic or extensive nodular or anaplastic/large cell medulloblastoma with appropriate and sufficient tumor material (FFPE or snap frozen) for proposed assays: all stages, age less than 6 years at diagnosis.
- Posterior fossa classic or anaplastic/large cell medulloblastoma with sufficient tumor material (FFPE or snap frozen) for proposed assays: clinically high-stage (neuraxis or extra-neural dissemination, M1-4), age greater than 6 years to less than 10 years at diagnosis.
- Posterior fossa medulloblastoma, those 6 years of age and above at diagnosis, will only be eligible if they have evidence of neuraxis or extraneural dissemination. Patients 6 years of age and above with low-stage (standard-risk, M0) medulloblastoma will NOT be eligible for this study, irrespective of molecular subgroup and extend of local resection.
Eligibility last updated 1/6/22. Questions regarding updates should be directed to the study team contact.
A Study Comparing Bi-parametric MRI to Multi-parametric MRI in the Diagnosis of Clinically Significant Prostate Cancer (PRIME)
Prostate Imaging Using MRI +/- Contrast Enhancement
- Men at least 18 years of age referred with clinical suspicion of prostate cancer.
- Serum PSA ≤ 20ng/ml.
- Fit to undergo all procedures listed in protocol.
- Able to provide written informed consent.
- Prior prostate biopsy.
- Prior treatment for prostate cancer.
- Prior prostate MRI on a previous encounter.
- Contraindication to MRI.
- Contraindication to prostate biopsy.
- Unfit to undergo any procedures listed in protocol.
Eligibility last updated 10/5/21. Questions regarding updates should be directed to the study team contact.
A Phase 1/1b, Open-label, Multicenter Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Anti-tumor Activity of KIN-3248 in Participants With Advanced Tumors Harboring FGFR2 and/or FGFR3 Gene Alterations
A Study to Evaluate KIN-3248 in Participants With Advanced Tumors Harboring FGFR2 and//or FGFR3 Gene Alterations
- Participant has provided written informed consent prior to initiation of any study-specific procedures.
- Men or women at least 18 years of age (or ≥ age of majority in local jurisdictions) at the time of signing the informed consent form (ICF).
- Histologically or cytologically confirmed diagnosis of advanced-stage malignancy, as follows:
- Part A
•Any type of advanced tumors harboring FGFR2 and/or FGFR3 gene alterations; - Part B Cohort 1
•Advanced ICC with FGFR2 gene alterations who previously demonstrated clinical benefit to FGFRi treatment and discontinued due to disease progression; - Part B Cohort 2
•Advanced UC with FGFR2 and/or FGFR3 gene alterations who previously demonstrated clinical benefit to FGFRi treatment and discontinued due to disease progression; - Part B Cohort 3
•Advanced ICC or UC with FGFR2 and/or FGFR3 gene alterations who are FGFRi naïve; - Part B Cohort 4
•Advanced solid tumors (other than ICC or UC) with FGFR2 and/or FGFR3 gene alterations who are FGFRi naïve or were previously treated with FGFRi.
- Part A
- Participants must have either received prior standard of care therapy (including FGFRrelated agents approved in local jurisdictions) appropriate for their tumor type and stage of disease or, in the opinion of the Investigator, be unlikely to tolerate or to derive clinically meaningful benefit from standard of care therapy (applicable to Parts A & B).
- In Part B Cohorts 1 and 2, participants with ICC or UC driven by FGFR2 and/or FGFR3 gene alterations should have previously received an FGFR inhibitor, approved by the local regulatory agency or as an investigational agent within a clinical trial where such treatment exists (hereafter referred to as “such treatment”). Additionally, such treatment must have resulted in clinical benefit, for example objective tumor shrinkage (i.e., complete response [CR] or partial response [PR]) or sustained disease control (i.e., continuous stable disease for at least 8 weeks) prior to confirmed progressive disease. In Cohorts 3 and 4, FGFRi naïve participants must have received at least one line of prior systemic therapy. In Cohort 4, other solid tumors previously treated with FGFRi do not need to have demonstrated clinical benefit to such treatment.
- Participant’s tumor has documented FGFR2 and/or FGFR3 alteration in blood and/or tumor per local assessment as detected by DNA sequencing using a comprehensive nextgeneration sequencing assay (e.g., FoundationOne® CDx or Guardant360® CDx), breakapart fluorescence in situ hybridization (FISH), or other validated assay. Potential participants harboring an amplification as the only FGFR2 or 3 alteration would not be considered eligible. Genomic analysis of tumor tissue or circulating tumor-derived (blood) nucleic acids (ctDNA) must have been conducted in a Clinical Laboratory Improvement Amendments (CLIA)- certified laboratory (in US) or in accordance with local regulatory requirements (in other countries).
- Willing to provide an archived tumor tissue specimen (formalin-fixed paraffin embedded [FFPE] specimen) obtained within the last 5 years, if available.
- Willing to undergo pre-treatment tumor biopsy, if medically feasible. The availability of a FFPE tumor biopsy specimen obtained within 2 months prior to consent from participants who have not received intervening systemic anti-cancer therapy will satisfy the pretreatment biopsy requirement.
- Measurable or evaluable disease by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. For Part B, measurable disease only.
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
- An estimated life expectancy of at least 3 months in the opinion of the Investigator.
- Adequate hematological lab assessments at screening, as follows:
- Absolute neutrophil count (ANC) ≥ 1000/mm^3 (1.0 x 10^9 /L);
- Platelet count ≥ 75,000/ mm^3 (75x 10^9 /L);
- • Hemoglobin ≥ 9.0 g/dL (at least 7 days since most recent blood transfusion).
- Adequate renal laboratory assessments, as follows:
- Estimated creatinine clearance ≥ 50 mL/min as calculated using the Cockcroft-Gault method or a method standard for the institution.
- Adequate hepatic laboratory assessments, as follows:
- ALT and aspartate transaminase ≤ 3 x upper limit of normal (ULN), or ≤ 5 x ULN in the presence of liver metastases;
- Serum total bilirubin ≤ 1.5 x ULN (< 3.0 x ULN for participants with documented Gilbert’s syndrome);
- ALP ≤ 2.5 x ULN (≤ 5 x ULN in case of bone metastasis, biliary tract involvement or liver metastases).
- Adequate chemistry laboratory assessments, as follows:
- Sodium ≥ 130 mEq/L or within institutional normal limits;
- Potassium ≥ 3.6 mmol/L or within institutional normal limits;
- Phosphate ≤ 1.5 x ULN.
- Able to swallow, retain, and absorb oral medications.
- Known clinically-active or clinically-progressive brain metastases from non-brain tumors
- History and/or current evidence of abnormal calcium-phosphorous homeostasis, ectopic mineralization or calcification, or corneal or retinal disorder/keratopathy
- GI tract disease causing an inability to take oral medication, malabsorption syndrome, requirement for intravenous alimentation, or uncontrolled inflammatory GI disease
- Active, uncontrolled bacterial, fungal, or viral infection
- Women who are lactating or breastfeeding, or pregnant
Note: Other protocol defined Inclusion/Exclusion Criteria may apply.
Eligibility last updated 10/9/23. Questions regarding updates should be directed to the study team contact.
A Phase 2 Study for the Evaluation of Safety and Efficacy of Humacyte’s Human Acellular Vessel for Vascular Replacement or Reconstruction in Patients with Life or Limb-threatening Vascular Trauma (CLN-PRO-V005)
Humacyte’s Human Acellular Vessel for Vascular Replacement or Reconstruction in Patients with Life or Limb-threatening Vascular Trauma
- Patients with life or limb threatening traumatic injury to an arterial vessel in the limb or torso, other than the heart, which requires replacement or reconstruction.
- Preoperative imaging or clinical examination indicates the damaged vessel has a defect length of ≤ 38cm and is appropriately size matched to the 6mm Human Acellular Vessel (HAV) per the judgment of the treating surgeon taking into account vasoconstriction and situational inflow and outflow considerations.
- Autologous vein graft is either not feasible in the judgment of the treating surgeon (e.g., because of lack of availability of suitable conduit, presence of severe venous insufficiency) or is not desirable because of the urgency of revascularization.
- Aged 18 to 85 years old, inclusive.
- Able to communicate meaningfully with investigative staff, and able to comply with entire study procedures. If the patient is unconscious, then information from a reliable witness indicates that the patient would normally be able to comply with study procedures.
- Patient or relative is able, willing and competent to give informed consent.
- Life expectancy of at least 1 year.
- Mangled Extremity Severity Score (MESS) of ≥ 7.
- Limb at high risk of amputation despite vascular reconstruction (e.g., because of crush injury).
- Catastrophic injuries that make survival unlikely (e.g., Abbreviated Injury Scale (AIS) > 5 or Injury Severity Score (ISS) > 60).
- HAV may not be used for coronary artery repair.
- Known pregnant women.
- Known medical condition which would preclude long term antiplatelet therapy after resolution of acute injuries.
- Any other condition which in the judgment of the investigator would preclude adequate evaluation of the safety and efficacy of the HAV.
- Previous exposure to HAV.
- Known participation in any investigational study within the last 30 days.
- Employees of the sponsor or patients who are employees or relatives of the investigator.
Eligibility last updated 3/22/22. Questions regarding updates should be directed to the study team contact.
Electrophysiologic and Biosensor Signal Analysis of Patients and Controls (PSA)
Electrophysiologic and Biosensor Signal Analysis of Patients and Controls
Subjects
- Clinically or genetically confirmed diagnosis of a neurological, psychiatric, or medical condition of interest.
- Age ≥ 18 years at time of diagnosis.
Controls
- Healthy control participants, either a convenience sample of patient’s friends, acquaintances, or family members; or alternatively, community controls, or control outpatients seen at Mayo Clinic.
- Age ≥ 18 years at time of survey.
Subjects
- Age < 18 years at time of diagnosis.
- Inadequate familiarity with the English language.
- Presence of any medical condition or surgical history that could affect the safety of the subject or interfere with study assessments, safety, or the ability of the subject to complete the evaluation per the judgment of the site principal investigator.
Controls
- Age < 18 years at time of survey.
- Inadequate familiarity with the English language.
- Presence of any medical condition or surgical history that could affect the safety of the subject or interfere with study assessments, safety, or the ability of the subject to complete the evaluation per the judgment of the site principal investigator.
- Personal history of the neurological, psychiatric, or medical conditions being studied.
Eligibility last updated 11/17/21. Questions regarding updates should be directed to the study team contact.
SALA-002-EW16, Phase 1 Trial of the LSD1 Inhibitor Seclidemstat (SP 2577) With and Without Topotecan and Cyclophosphamide in Patients With Relapsed or Refractory Ewing Sarcoma and Select Sarcomas
Clinical Trial of SP-2577 (Seclidemstat) in Patients With Relapsed or Refractory Ewing or Ewing-related Sarcomas
Inclusion Criteria
•All Patients:
- Age ≥ 12 years.
- Weight ≥ 40 kg.
- Karnofsky ≥ 70% for over ≥ 16 years old and Lansky ≥ 70% for under 16 years old, equivalent to Eastern Cooperative Oncology Group (ECOG) performance status Grade 0 or 1.
- Life expectancy of greater than 4 months in investigator's opinion.
- Willingness to provide tumor biopsies during screening and while on treatment. Optional for patients < 18 years of age and patients enrolled in the Ewing sarcoma combination treatment arm. Biopsies can be exempt if deemed by the investigator that the biopsy is not medically feasible for the patient or the patient is unfit for the procedure.
- Normal organ and marrow function as defined below:
- absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L;
- platelets ≥ 100 x 10^9/L; no transfusion 7 days prior to labs;
- total bilirubin ≤ 1.5 x upper limit of normal (ULN) or, in patients with Gilbert syndrome, total bilirubin > 1.5 x ULN as long as direct bilirubin is normal;
- AST and ALT ≤ 3 x ULN;
- Creatinine ≤ 1.5 x ULN OR creatinine clearance ≥ 60 mL/min/1.73 m^2 for patients with creatinine levels above normal.
- Ability to understand and the willingness to sign a written informed consent document. Additional Inclusion Criteria for Ewing Sarcoma Combination Treatment Cohort.
- Patients must have a histologic confirmed diagnosis of Ewing sarcoma with a known EWSR1 translocation through local assessment that is relapsed or refractory and must have received at least one prior course of therapy for Ewing sarcoma. For the purposes of this study, refractory disease is defined as metastatic or unresectable disease that has either progressed or is stable at completion of planned therapy.
- Patients must have had no more than 2 lines/courses of systemic treatment for Ewing sarcoma.
- No prior therapy with the combination regimen of topotecan and cyclophosphamide. Prior cyclophosphamide is allowed if not combined with topotecan.
- Patients must have measurable disease by computed tomography (CT) or magnetic resonance imaging (MRI) based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
Additional Inclusion Criteria for Single Agent Myxoid Liposarcoma Cohort and for Single Agent FET-Translocated Sarcomas:
- Patients must have a histologic confirmed diagnosis of one of the following sarcomas that share similar known chromosomal translocations to Ewing sarcoma (per local assessment) and are relapsed or refractory and not amenable to surgery at time of enrollment.
- Patients must have received at least one prior course of systemic therapy but no more than 3 courses of systemic therapy for sarcoma.
- Patients must have measurable disease by computed tomography (CT) or magnetic resonance imaging (MRI) based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
Exclusion Criteria for All Patients:
- Patients who have not recovered to Grade 1 or baseline from adverse events related to prior therapy excluding lymphopenia, alopecia, peripheral neuropathy and ototoxicity, which are only exclusionary if original AE was ≥ CTCAE Grade 3.
- Patients receiving therapy with other anti-neoplastic or experimental agents.
- Prior therapy with LSD1 targeted agents including monoamine oxidases for cancer therapy.
- Prior oral tyrosine kinase inhibitors (i.e. sorafenib, pazopanib, regorafenib, cabozantanib) within 14 days of Cycle 1 Day 1.
- Other, prior systemic anti-cancer treatment (chemotherapy or biologic therapy [i.e., monoclonal antibodies]) within 21 days prior to Cycle 1 Day 1. For agents that have known adverse events occurring beyond 21 days after administration, this period must be extended beyond the time during which adverse events are known to occur. The duration of this interval must be discussed with the Medical Monitor.
- Prior therapy with immunotherapy such as a checkpoint inhibitor, cellular therapy or vaccine therapy within 28 days prior to Cycle 1 Day 1.
- Patients must have recovered from any immune-related adverse events to Grade 1 or baseline and require ≤ 10 mg of prednisone equivalent daily. Patients with immune-related hypothyroidism and/or hypoadrenalism may enroll while on thyroid or hydrocortisone replacement therapy, respectively.
- Prior small port palliative radiotherapy within 14 days of Cycle 1 Day 1 or within 42 days of Cycle 1 Day 1 from definitive local control radiation (any dose greater than 50 Gy, within 42 days of Cycle 1 Day 1).
- Prior therapy with long acting myeloid growth factor within 14 days of Cycle 1 Day 1 or within 7 days of Cycle 1 Day 1 from a short acting myeloid growth factor.
- Evidence of graft versus host disease or prior allo- or auto-bone marrow transplant or stem cell infusion within 84 days from Cycle 1 Day 1 or receiving immunosuppressants following a stem cell procedure.
- Participation in a prior investigational study within 30 days prior to Cycle 1 Day 1 or within 5 half-lives of the investigational product, whichever is longer.
- Progressive or symptomatic brain metastases; patients with brain metastases may be included in this trial as long as the brain metastases have received definitive treatment and are stable (i.e., no evidence of progression). The brain metastases must be stable for a minimum of 6 weeks prior to Cycle 1 Day 1.
- Currently receiving any of the following substances and cannot be discontinued 14 days or 5 half-lives for CYP inhibitors (whichever is shorter) prior to Cycle 1 Day 1:
- moderate or strong inhibitors or inducers of major CYP isoenzymes, including grapefruit, grapefruit hybrids, pomelos, star fruit, and Seville oranges;
- moderate or strong inhibitors or inducers of major drug transporters;
- substrates of CYP3A4/5 with a narrow therapeutic index.
- Uncontrolled concurrent illness including, but not limited to:
- ongoing or active infection -transfusion dependent thrombocytopenia or anemia;
- psychiatric illness/social situations that would limit compliance with study requirements; discuss with Medical Monitor if there are any questions.
- Clinically significant, uncontrolled heart disease and/or cardiac repolarization abnormality, including any of the following:
- symptomatic congestive heart failure;
- left ventricular ejection fraction (LVEF) ≤ 50%;
- unstable angina pectoris or cardiac arrhythmia;
- baseline QTc (Fridericia) ≥ 450 milliseconds;
- long QT syndrome or family history of idiopathic sudden death or congenital long QT syndrome.
- Any major surgery within 21 days prior to Cycle 1 Day 1. Major surgery is defined as any significantly invasive procedure into a major body cavity (abdomen, cranium etc.) and/or surgery requiring extensive recuperation (joint replacement). Please discuss with Medical Monitor if there are any questions.
- Pregnant and breastfeeding women are excluded from this study. The effects of seclidemstat on the developing human fetus have the potential for teratogenic or abortifacient effects.
- Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of seclidemstat administration.
- HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with seclidemstat. In addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy.
Eligibility last updated 2/11/22. Questions regarding updates should be directed to the study team contact.
Venoarterial ECMO vs Off-Pump Bilateral Orthotopic Lung Transplantation VIP BOLT Trial: A Multicenter Prospective Randomized Trial (VIP BOLT)
A Trial of Venoarterial ECMO vs Off-Pump Bilateral Orthotopic Lung Transplantation
- Bilateral Lung Transplantation (LTx) recipients.
- Mean pulmonary artery pressure < or = 35 mmHg.
- Eligible for off-pump or VA ECMO based on the judgement of the attending surgeon.
- Single lung transplant
- Multiorgan transplant.
- Donor after cardiac death (DCD).
- Re-transplant.
- Intention to use prophylactic post-operative ECMO.
- Previous major lung surgery. Video-assisted thoracoscopic surgery (VATS) and wedge
resection are not an exclusion criterion.
- Previous pleurodesis.
- Preoperative ECMO and/or mechanical ventilation.
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Eligibility last updated 6/29/23. Questions regarding updates should be directed to the study team contact.
A Qualitative Approach to Understanding Financial Toxicity in Management of Advanced Prostate Cancer
Understanding Financial Toxicity in Management of Advanced Prostate Cancer from Qualitative Approach
- Age 18 years and older, diagnosed with metastatic prostate cancer.
- Have an additional non-prostate cancer diagnosis, have non-metastatic prostate cancer recurrence.
Eligibility last updated 6/7/22. Questions regarding updates should be directed to the study team contact.
ALKS 4230-006, A Phase 2, Open-Label, Multicenter, Cohort Study of Nemvaleukin Alfa (ALKS 4230) Monotherapy in Patients With Advanced Cutaneous Melanoma or Advanced Mucosal Melanoma Who Have Previously Received Anti-PD-[L]-1 Therapy - ARTISTRY-6 (ARTISTRY-6)
Nemvaleukin Alfa (ALKS 4230) Monotherapy in Patients With Advanced Cutaneous Melanoma or Advanced Mucosal Melanoma
- The patient must have the following tumor types:
Cohort 1: Patient has unresectable and/or metastatic cutaneous melanoma. No more than 5
patients with acral melanoma may enroll in this cohort.
Cohort 2: Patient has unresectable and/or metastatic mucosal melanoma.
Cohort 3: Patient has unresectable and/or metastatic cutaneous melanoma. Patients with
acral melanoma may not enroll in this cohort.
- The patient must have received previous treatment as follows:
1. Patient has received anti-PD-[L]1 therapy with or without anti-CTLA-4 therapy,
and no more than one other prior regimen of systemic anti-neoplastic therapy (eg,
targeted therapy, chemotherapy). Previous adjuvant and/or neoadjuvant therapy
counts as one prior regimen.
2. Patients have experienced objective response (partial response [PR] or CR; by
RECIST 1.1 or iRECIST) or stable disease (SD; by RECIST 1.1 or iRECIST) as best
overall response (BOR) to anti-PD-[L]1 therapy. Patients with confirmed
progressive disease (by RECIST 1.1 or iRECIST) as best response may be included,
if they received anti-PD-[L]1 therapy for a minimum of 12 weeks (eg, from first
dose to last dose).
3. Patients with BRAF mutations may or may not have received prior targeted therapy.
- Patients must have disease that is measurable based on RECIST 1.1., that has not
recently been irradiated or used to collect a biopsy.
- Patient is willing to undergo a pretreatment tumor biopsy or provide qualifying
archival tumor tissue.
- Patient has an Eastern Cooperative Oncology Group (ECOG) status of 0 or 1 and an
estimated life expectancy of ≥3 months.
- Additional criteria may apply.
- Patient has uveal melanoma (all cohorts) or acral melanoma (Cohort 2 and Cohort 3).
- Patient has received prior interleukin (IL)-2-based or IL-15-based cytokine therapy;
patient has had exposure, including intralesional, to IL-12 or analogs thereof.
- Patient requires systemic corticosteroids (>10 mg of prednisone daily, or equivalent)
however, replacement doses, topical, ophthalmologic, and inhalational steroids are
permitted.
- Patient has undergone prior solid organ and/or non-autologous hematopoietic stem cell
or bone marrow transplant.
- Patient is currently pregnant, breastfeeding, or is planning to become pregnant or to
begin breastfeeding during the study period or within 30 days after last study drug
administration.
- Patients with active or symptomatic central nervous system metastases unless the
metastases have been treated by surgery and/or radiation therapy and/or gamma knife,
the subject has been tapered to a dose of 10 mg of prednisone (or equivalent) or less
of corticosteroids for at least 2 weeks before the first dose, and the subject is
neurologically stable. Patients with leptomeningeal disease are excluded.
- Patient has known or suspected hypersensitivity to any components of nemvaleukin.
- Patients with an uncontrollable bleeding disorder.
- Patient has QT interval corrected by the Fridericia Correction Formula values of >470
msec (in females) or >450 msec (in males); patient who is known to have congenital
prolonged QT syndromes; or patient who is on medications known to cause prolonged QT
interval on ECG.
- Patient has developed Grade ≥3 immune-related AEs (irAEs) while on prior
immunotherapy, (eg, pneumonitis and nephritis) and has not recovered to ≤Grade 1
and/or are on systemic steroids within 14 days of first dose of study drug.
- Patients who have previously discontinued immunotherapy due to immune-related adverse
event (irAEs) will be excluded.
- Additional criteria may apply.
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Eligibility last updated 4/17/23. Questions regarding updates should be directed to the study team contact.