• Subjects or their Legally Authorized Representative (LAR) must provide written informed consent to the study procedures prior to any study procedures.
• Subjects must have a caregiver/ study partner who in the opinion of the site principal investigator, has contact with the study subject for a sufficient number of hours per week to provide informative responses on the protocol assessments, oversee the administration of study drug, and is willing and able to participate in all clinic visits and some study assessments.
• Men or women 50-85 years of age (inclusive), meeting criteria for probable Dementia with Lewy Bodies (DLB).
• Men willing to comply with acceptable form of contraception or women of non-childbearing.
• Willingness to undergo a lumbar puncture (LP) during the screening period and at the end of the 6-month treatment period.
• Formal education of eight or more years.
• Subjects living at home or in an assisted living facility.
• Subjects shall be generally healthy with mobility, vision and hearing sufficient for compliance with testing procedures.
• Must be able to complete all screening evaluations.

• Any neurological condition that may be contributing to cognitive impairment above and beyond those caused by the subject's DLB, including any co-morbidities detected by clinical assessment or MRI (or CT scan due to contraindication of MRI, if approved by medical monitor).
• History of transient ischemic attacks or stroke within 12 months of screening.
• Parkinsonian (extrapyramidal) features with Modified Hoehn and Yahr stage 4 or higher or any diagnosis of Parkinson’s disease or parkinsonism that preceded cognitive decline by more than one year.
• Hospitalization (except for planned procedures) or change of chronic concomitant medication within one month prior to screening.
• Any major psychiatric diagnosis, including schizophrenia, bipolar disorder, and current major depressive disorder as per Diagnostic and Statistical Manual of Mental Disorders Fifth Edition.
• Geriatric Depression Scale score > 6. (Subjects with a GDS > 6 may be allowable if the investigator does not believe the subject is clinically depressed. Investigators should contact the medical monitor to discuss eligibility).
• Subjects living in a continuous care nursing facility.
• Contraindication to the MRI examination for any reason (CT scan may be substituted for an MRI if subjects are unable to tolerate an MRI or an MRI is contraindicated for medical reasons, if the proposed CT scan is discussed and approved by the medical monitor on a case-by-case basis).
• Screening MRI (or historical MRI or CT scan due to contraindication of MRI if approved by medical monitor) or historical MRI/CT scan, if applicable. of the brain indicative of significant abnormality, including, but not limited to, prior hemorrhage or infarct >1 cm3 , > 3 lacunar infarcts, cerebral contusion, encephalomalacia, aneurysm, vascular malformation, subdural hematoma, hydrocephalus, space-occupying lesion (e.g., abscess or brain tumor such as meningioma). If a small incidental meningioma is observed, the medical monitor may be contacted to discuss eligibility.
• Clinical, laboratory findings or medical history consistent with:
  • Other primary degenerative dementia, (frontotemporal dementia, Huntington’s disease, Creutzfeldt-Jakob Disease, Down syndrome, etc.);
  • Other neurodegenerative condition (amyotrophic lateral sclerosis, etc.);
  • Seizure disorder;
  • Other infectious, metabolic or systemic diseases affecting the central nervous system (syphilis, present hypothyroidism, present vitamin B12 or folate deficiency, other laboratory values etc.).
• Clinically significant, advanced or unstable disease that may interfere with outcome evaluations, such as:
  • Chronic liver disease, liver function test abnormalities or other signs of hepatic insufficiency (ALT, AST, alkaline phosphatase > 1.5 ULN, lactate dehydrogenase (LDH) > 1.5 x ULN);
  • Respiratory insufficiency which requires the use of supplemental oxygen;
  • Renal insufficiency eGFR < 50 mL/min based on the CKD‐EPI formula;
  • Heart disease (myocardial infarction, unstable angina, heart failure, cardiomyopathy within six months before screening);
  • Bradycardia (100 beats/min.). If heart rate is below 50 beats/min or above 100 beats/min, the heart rate assessment may be repeated to assess eligibility;
  • Poorly managed hypertension (systolic > 160 mm Hg and/or diastolic > 95 mm Hg) or hypotension (systolic 7.5% in subjects with diabetes, only those subjects with known diabetes are required to get a HbA1c at screen.
• History of cancer within 3 years of screening with the exception of fully excised non-melanoma skin cancers or non-metastatic prostate cancer that has been stable for at least 6 months.
• Seropositive for human immunodeficiency virus (HIV).
• History of acute/chronic hepatitis B or C and/or carriers of hepatitis B (seropositive for hepatitis B surface antigen [HbsAg] or anti-hepatitis C [HCV] antibody).
• Clinically significant abnormalities in screening laboratory tests, including:
  • Hematocrit less than 35% for males and less than 32% for females, absolute neutrophil cell count of 1500/uL (with the exception of a documented history of a chronic benign neutropenia, absolute lymphocyte count 1.4 or other coagulopathy, confirmed by repeat assessment of:
  • Hematocrit;
  • Neutrophil count;
  • Lymphocyte count;
  • Platelet count.
• Disability that may prevent the subject from completing all study requirements (e.g., blindness, deafness, severe language difficulty, etc.).
• Within 4 weeks of screening visit or during the course of the study, concurrent treatment with antipsychotic agents, antiepileptics, centrally active antihypertensive drugs (e.g., clonidine, l-methyl dopa, guanidine, guanfacine, etc.), sedatives, opioids, mood stabilizers (e.g., valproate, lithium); or benzodiazepines, with the following exceptions:
  • At the discretion of the investigator, lorazepam or another anxiolytic may be administered as per local standard of care prior to MRI scan or optional lumbar puncture. Note neurocognitive testing should not be done within 24 hours of administration of conscious sedation;
  • Stable use of clonazepam for at least 30 days as indicated for REM Sleep Behavioral Disorder (RBD);
  • Stable use of atypical antipsychotics (e.g., quetiapine, pimavanserin) for at least 30 days as indicated for delusions and hallucinations secondary to DLB.
• Any disorder that could interfere with the absorption, distribution, metabolism, or excretion of drugs (e.g., small bowel disease, Crohn’s disease, celiac disease, or liver disease).
• Nootropic drugs except stable AD meds (acetylcholinesterase inhibitors or memantine).
• Suspected or known drug or alcohol abuse; i.e., more than approximately 60 g alcohol (approximately 1 liter of beer or 0.5 liter of wine) per day indicated by elevated MCV significantly above normal value at screening.
• Suspected or known allergy to any components of the study treatments.
• Enrollment in another investigational study or intake of investigational drug within the previous 30 days or five half-lives of the investigational drug, whichever is longer.
• Intake of drugs or substances potentially involved in clinically significant induction or inhibition of CYP3A4 or P-gp mediated drug interactions with CT1812, within 4 weeks or five half-lives of the interacting drug prior to administration of CT1812 and throughout the course of the study. Grapefruit juice should be avoided in the two weeks prior to dosing and throughout the course of the study. 
• Any prior exposure to immunomodulators, anti Aβ vaccines, or passive Aβ immunotherapies (e.g., monoclonal antibodies) and/or exposure to BACE inhibitors within the past 30 days.
• Any condition, which in the opinion of the investigator or the sponsor makes the subject unsuitable for inclusion.
• Any vaccination within one week of the baseline visit.

Eligibility last updated 5/23/23. Questions regarding updates should be directed to the study team contact.

• Male or female age ≥ 18 years.
• Is able and willing to provide written informed consent, which includes compliance with study requirements and restrictions listed in the consent form.
• Have a ≥ 6-month history of documented sarcoidosis including histological confirmation in the subject’s medical records.
• Have high-resolution computed tomography (HRCT) and PET scan consistent with active pulmonary sarcoidosis of the lung parenchyma confirmed by central read.
• Have FVCp ≥ 50% to ≤ 90% and DLCO ≥ 50%.
• If receiving prednisone (or equivalent), dose must have been ≤25 mg, and dose must have been stable for at least 4 weeks prior to randomization.
• Symptomatic as indicated by mMRC Dyspnea scale >1 (i.e., Grade 2 or more) in the prior year.
• If receiving methotrexate and/or other immunosuppressive therapy (IST) dose must have been stable for ≥ 3 months prior to randomization.
• Female subjects must agree to use an approved highly effective birth control (BC) method (< 1% failure rate per year) throughout the study, unless documented to have a reproductive status of non-childbearing potential or is postmenopausal:
  • Non-childbearing potential defined as pre-menopausal female with medical history of bilateral tubal ligation, bilateral oophorectomy (removal of the ovaries), or hysterectomy; hysteroscopic sterilization;
  • Postmenopausal defined as 12 months of spontaneous amenorrhea; otherwise, a follicle stimulating hormone (FSH) confirmation will be required. For females with questionable menopausal history (e.g., irregular menstrual periods and age > 40 years) a documented serum FSH level must be ≥ 30 mIU/mL;
  • Woman of childbearing potential (WCBP) who is already using an established method of highly effective contraception or agrees to use one of the allowed BC methods, for at least 28 days prior to the start of dosing, throughout the study, and for 4 months following the last dose of study drug.
• Males who are sexually active must agree to use one of the allowed BC methods. Male subjects must also agree to sufficiently minimize the risk of pregnancy throughout study participation (and for 4 months following the last dose of study drug).
• Body Mass Index (BMI) 18 to 40 kg/m^2 at screening.
• Subjects must agree to steroid taper, and cessation of their IST therapy at randomization.
• Completion of vaccination for COVID-19 at least 2 weeks prior to randomization.

Exlusion Criteria:

• Hospitalized for any respiratory illness ≤ 30 days prior to screening.
• Prednisone dose > 25 mg/day at any time in the previous 4 weeks.
• ≥ 20% fibrosis as indicated on CT-scan that has been confirmed by central read prior to randomization.
• eGFR ≤30 mL/min/1.73 m^2 (MDRD equation) or requiring hemofiltration or dialysis.
• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) > 3 × upper limit of normal range (ULN).
• Platelet count <100,000 per mm^3.
• Hemoglobin ≤ 9.5 g/dL.
• Absolute neutrophil count < 1,000 per mm^3.
• History of known anti-GM-CSF autoAb or tests positive at screening, or history of pulmonary alveolar proteinosis (PAP).
• Use of biologic — approved or investigational agents (e.g., anti-TNFα, anti-IL-1, anti-IL-6, anti-IL-17, anti-IL-12/23 or specific anti-IL-23 inhibitors, anti CD20, anti-IL-18) within the 6 months prior to screening.
• Prior use of immunoglobulin within 6 months prior to screening.
• Prior use of any investigational immunomodulator (e.g., NRP2 modulator) within 6 months of screening.
• Prior use of any JAK inhibitor within 3 months of screening.
• Participation in another interventional clinical trial within 6 months prior to screening.
• Known left ventricular ejection fraction (LVEF) ≤30% or NYHA class III or IV heart failure.
• ECG abnormalities that warrant further investigation, in the opinion of the Investigator.
• Pulmonary hypertension requiring therapy.
• Systolic blood pressure (SBP)  < 90 or > 180 mm Hg; Diastolic blood pressure (DBP) < 60 or > 110 mm Hg.
• Known COVID-19 infection within 3 months prior to screening.
• Have received any live virus or bacterial vaccinations < 3 months of screening. Age-appropriate non-live vaccinations may be administered during screening so long as the last vaccine dose is administered at least 2 weeks prior to planned randomization.
• Any infection requiring antibiotics or pulse of OCS where completion of treatment has been < 30 days prior to screening.
• History of 3 or more lower respiratory tract infections requiring anti-microbial therapy in the past year.
• Any history of mycetoma or fungal respiratory infection.
• Requirement for supplemental oxygen at rest.
• Prior history of, or likely to have any organ transplantation during study including OLE.
• History of smoking (or vaping) in the prior year or current use. Occasional use (defined as less frequently than once per month) is allowable, though subjects should be counseled to remain abstinent during the study including OLE.
• Other significant pulmonary disease likely to interfere with the primary endpoint, in the opinion of the Investigator.
• Other autoimmune disease likely to require therapy during the study.
• Symptoms and features of extra-PS that may warrant treatment in addition to that required for lung involvement.
• Significant ischemic heart disease (i.e., myocardial infarction within 6 months, unstable angina or PCTA/stent within 1 month or planned intervention during study).
• Known or suspected active and untreated/inadequately treated tuberculosis (TB), human immunodeficiency virus (HIV), hepatitis B or C infection. Subjects with latent TB may be enrolled if anti-TB therapy is commenced prior to randomization.
• For women: pregnant or planning to become pregnant during the study or currently breastfeeding.
• Prior history of any malignancy or lymphoproliferative disorder (not including fully resected basal cell carcinoma of the skin, fully resected intra-epithelial neoplasia or carcinoma in situ) within the past 5 years.

Eligibility last updated 12/23/21. Questions regarding updates should be directed to the study team contact.

•  All female patients that have undergone open prophylactic NSM cases performed between January 1, 2018 through 42 days prior to IRB approval.

• Patients who have not undergone open prophylactic NSM surgery.

Eligibility last updated 12/29/21. Questions regarding updates should be directed to the study team contact.

• Diagnosis of CVID according to the international consensus document (ICON):
  • Age 4 years or above;
  • Serum IgG at least 2 standard deviations below the age adjusted normal;
  • Decreased serum IgA and/or serum IgM;
  • Abnormal specific antibody response to immunization;
  • Exclusion of secondary immunodeficiency.
• On replacement immunoglobulin for at least 6 months and willing to maintain throughout study.
• Granulomatous-lymphocytic interstitial lung disease with a lymphocytic component diagnosed by lung biopsy prior to study entry, wedge biopsy preferred.
• Persistence or worsening of interstitial lung disease measured on serial CT imaging of the lung at least 6 months apart, with the latest assessment within 2 months of study entry.
• Signed written informed consent.
• Willing to allow storage of biological specimens for future use in medical research.
• Females of childbearing potential must use a highly effective form of birth control such as hormone-based contraceptive, intrauterine device, or double barrier method.

• History of hypersensitivity to abatacept or any of its components.
• Has received any lymphocyte depleting agents including anti-CD20 monoclonal antibodies, alemtuzumab, ATG in the preceding 6 months.
• Has received abatacept, cyclophosphamide, tumor necrosis factor inhibitors, or pulse steroids (defined as >15mg/kg/day of methylprednisone or corticosteroid equivalent) within the past 3 months.
• History of HIV infection (positive PCR).
• Chronic untreated hepatitis B or C (positive PCR).
• Active tuberculosis (TB) by positive QuantiFERON gold. If history of latent TB, then must supply evidence of completing treatment.
• Persistent Epstein-Barr Virus (EBV) load ≥ 1,000 units/mL blood checked twice at least 1 month apart.
• Other uncontrolled infections.
• Live vaccine given within 6 weeks of the start of the trial.
• Malignancy or treated for malignancy within the past year.
• Currently pregnant or breast feeding.
• Life expectancy less than 1 month.
• Subjects unwilling to self-administer or have a parent/caregiver self-administer subcutaneous injections at home.
• Other conditions that the investigators feel contraindicate participation in the study.

Eligibility last updated 12/22/21. Questions regarding updates should be directed to the study team contact.

• Diagnosed with a CNS hypersomnia according to ICSD-3 classifications.
• Age 18
  •75 years.
• BMI between 18 and 40 kg/m^2.
• Prescribed a medication of interest (e.g., sodium oxybate, low sodium oxybate, pitolisant, modafinil/armodafinil, solriamfetol) by a clinical sleep specialist as part of routine medical care and covered by subject’s health insurance plan.
• If subject has not yet started the prescribed medication, then subject must be willing to postpone starting medication until after completion of baseline assessment(s).
• If subject has been taking a prescribed medication at a stable dose for at least 3 months and has been prescribed a new medication, then then subject may complete baseline assessment(s) while taking initial medication before starting new medication.

• Any change to medication(s) within the last 45 days.
• History of chronic alcohol or drug abuse within the prior 12 months.
• Heart failure, history of severe hypertension, or other cardiovascular disease compromising the patient's wellbeing or ability to participate in this study.
• Use of any sleep apnea treatment (e.g., Positive Airway Pressure (PAP) therapy, oral appliance therapy, etc.) within 45 days of baseline assessment visit.
• Participation in another study of an investigational drug within the 28 days prior to screening visit or currently.
• Pregnancy and/or breast-feeding.
• Subjects who, in the opinion of the Investigator, may not be suitable for the study.                     

Eligibility last updated 4/28/22. Questions regarding updates should be directed to the study team contact.

• Eligible patients are females with stage I-III breast cancer taking adjuvant AI (either standard dose of anastrozole 1 mg daily or letrozole 2.5 mg daily or exemestane 25 mg daily) for greater than 30 days experiencing AI induced musculoskeletal pain scores of 5 or higher on a Likert scale will be enrolled. Treating physicians determine if pain is secondary to an AI.  
• ≥ 18 years old.
• Subjects should have completed any planned surgery for breast cancer, chemotherapy and radiation therapy at least 30 days prior to enrollment.
• Patients should have an ECOG performance score of 0-2. 

•  Age less than 18 years.
• Significant underlying pulmonary disease.

Eligibility last updated 1/14/22.  Questions regarding updates should be directed to the study team contact.

• Diagnosis of one of one of the syndromes/diagnoses of interest using established criteria.
• Age ≥ 40 to ≤ 90 inclusive.
• STMS score above 10.
• No active medical disorder that could preclude participation.
• Stable medication regimen over previous four weeks.
• Absence of certain medications that could significantly impact the myocardial 123I-MIBG.
• For those with dementia, caregiver that is with the patient at least four hours/day for at least five days per week.
• For those with dementia , or severe parkinsonism, patient and caregiver willing and able to participate in all study-related procedures.
• Patient is capable of giving informed consent, or if apropriate, has caregiver capable of giving consent on the subject's behalf.

• Does not fulfill criteria for any of the desired diagnoses.
• Age > 40 or < 90.
• Women with intact uterus and not post-menopausal unless pregnancy test performed at screening is negative.
• Women who are pregnant or are breast-feeding an infant.
• STMS score < 10.
• Active medical disorder that could preclude participation in this protocol:
  • Hypersensitivity to the radioligand or iodine;
  • Myocardial infarction or cerebral infarct over preceding year, stable or unstable angina, known symptomatic coronary artery disease;
  • Renal disease viewed by the physician to be too severe to warrant myocardial 123I-MIBG scintigraphy imaging;
  • History of significant alcohol or drug abuse;
  • Any other medical disorder considered by the study physicians as inappropriate for enrollment in this protocol.
• Patient or caregiver unwilling or unable to participate in all study-related procedures.
• Caregiver is not with a patient with dementia or severe parkinsonism at least 4 hours/day for at least 5 days/week.
• Patient or caregiver unwilling or unable to provide informed consent.

Eligibility last updated 1/4/22. Questions regarding updates should be directed to the study team contact.

• Age ≥ 18 years.
• Age and gender matched to biorepository cohort.
• Population specific: 
  • For the never-COVID group – no history of having contracted COVID;
  • For COVID infection without post COVID cohort (+ COVID,
    •PASC), part of initial acute COVID biorepository;
  • time from onset of symptoms matched to biorepository cohort. 
  • For the + PASC group Included in the PASC biorepository.
• Matched by age, sex and time of onset of symptoms, as appropriate be able to participate fully in all aspects of the study; and  
• Have understood and signed study informed consent. 

• Active persistent COVID infection. 
• < 40 kg in weight have a known history of any condition or factor judged by the investigator to preclude participation in the study or which might hinder adherence. 
• Women with a previously confirmed infection with the novel SARS-CoV-2 virus of childbearing potential and pregnant women will be offered enrollment because there is no risk to an unborn child in this investigation.   

Eligibility last updated 3/2/22. Questions regarding updates should be directed to the study team contact.

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Eligibility last updated 2/1/23. Questions regarding updates should be directed to the study team contact.

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Eligibility last updated 5/9/23. Questions regarding updates should be directed to the study team contact.

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Eligibility last updated 4/6/23. Questions regarding updates should be directed to the study team contact.

Index Participants will be eligible if they:

• Are an ANAI person (based on self-reported race/ethnicity) and reside in Alaska.
• Are aged ≥ 21 years (legal smoking age in Alaska).
• Self-report smoking in the past 7 days, biochemically verified with breath expired air carbon monoxide (CO) > 4 ppm and saliva cotinine > 30 n/ml (positive Alere iScreen result).
• Smoked > 3 cigarettes per day (cpd) over the past 3 months.
• If other tobacco or nicotine product used, cigarettes are the main tobacco product used.
• Are considering or willing to make a quit attempt.
• Own or have access to a mobile phone or tablet with Internet and text messaging capabilities, or will be loaned an iPad mini for the study duration.
• Nominate one adult family member who will enroll.

• Used pharmacotherapy or a stop smoking program within the past 3 months.
• Another person in the household is enrolled as the index participant.

Family Member Participants, regardless of smoking status or residence with the index participant, will be eligible if they:

• Are ≥ 21 years old.
• Are defined as family by the index participant.
• Own or have access to a mobile phone or tablet with internet and text messaging capabilities or will be loaned an iPad mini for the study duration.
• Both men and women and those from non-ANAI racial/ethnic groups.
• Family members may only support one index participant to mitigate concern about lack of independence of household or other support networks, and potential for crosstreatment contamination, which could attenuate effects in the RCT.

Alaska Tribal Health System stakeholders:

• Input from healthcare providers, cessation specialists, and THO leaders will be gathered to understand potential facilitators and barriers to adoption of the intervention within the ATHS. The ANTHC team will invite individuals to participate through phone and email communications.

Eligibility last updated 1/17/22. Questions regarding updates should be directed to the study team contact.

• All patients that underwent cochlear implantation at the Mayo Clinic starting 1/1/1982.
• If patients declined MN research authorization, they may be contacted for consent for approval.

• Patients that did not undergo cochlear implantation at the Mayo Clinic.

Eligibility last updated 1/7/22. Questions regarding updates should be directed to the study team contact.

• Age ≥ 18 years.
• Cytologically or histologically confirmed colorectal cancer.
• Undergoing biopsy or surgical procedures as part of routine clinical care.

• Individuals < 18 years.
• Vulnerable patients.
• Unable to provide informed consent.

Eligibility last updated 1/7/22. Questions regarding updates should be directed to the study team contact.

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.

• Age > 25 or  < 65 years (to avoid studying subjects who could have latent type 1 diabetes, or the effects of age extremes in subjects with normal or impaired fasting glucose).
• HbA1c ≤ 8.5%.
• BMI ≥ 28 Kg/M^2.
• Use of insulin sulfonylureas or metformin only.
• For female subjects: negative pregnancy test at the time of enrollment or study.
• No history of prior upper abdominal surgery such as adjustable gastric banding, pyloroplasty and vagotomy.
• No active systemic illness or malignancy.
• No symptomatic macrovascular or microvascular disease.
• Any contraindications to MRI (e.g., metal implants, claustrophobia).
• Hematocrit > 35%.
• TSH > 0.4 or < 5.5.
• Consumption of < 2 alcohol drinks per day or < 14 per week or a negative AUDIT questionnaire.

• Age < 25 or > 65 years (to avoid studying subjects who could have latent type 1 diabetes, or the effects of age extremes in subjects with normal or impaired fasting glucose).
• HbA1c ≥ 8.5%.
• BMI ≤ 28 Kg/M^2.
• Use of insulin or agents other than sulfonylureas or metformin.
• For female subjects: positive pregnancy test at the time of enrollment or study.
• History of prior upper abdominal surgery such as adjustable gastric banding, pyloroplasty and vagotomy.
• Active systemic illness or malignancy.
• Symptomatic macrovascular or microvascular disease.
• Contraindications to MRI (e.g. metal implants, claustrophobia).
• Hematocrit < 35%.
• TSH < 0.4 or > 5.5.
• Consumption of > 2 alcohol drinks per day or > 14 per week or a positive AUDIT questionnaire.

Eligibility last updated 1/10/22. Questions regarding updates should be directed to the study team contact.

Inclusion Criteria
•Patient:

• Hospitalized patients (age ≥ 18 years) with high-risk AML defined as:
  • Patients with new diagnosis ≥ 60 years of age;
  • An antecedent hematologic disorder;
  • Therapy related-disease;
  • Relapsed or primary refractory AML.
• Receiving treatment with either:
  • intensive chemotherapy (7+3) or modification of this regimen on a clinical trial, or a similar intensive regimen requiring prolonged hospitalization; or
  • hypomethylating agents +/- additional agents or modification of this regimen on a clinical trial.

Inclusion Criteria
•Caregiver:

• Adult (≥ 18 years) relative or friend of a participating patient who the patient identifies as living with or has in-person contact with them at least twice per week.

Exclusion Criteria
•Patient:

• Patients with a diagnosis of acute promyelocytic leukemia (APML).
• Patients with AML receiving supportive care alone.
• Patients with psychiatric or cognitive conditions which the treating clinicians believe prohibits informed consent or compliance with study procedures.

Eligibility last updated 5/10/22. Questions regarding updates should be directed to the study team contact.

Case

Eligibility last updated 9/26/22. Questions regarding updates should be directed to the study team contact.

Inclusion Criteria
•Obese Subjects with Type 2 Diabetes:

• Age ≥ 25 or ≤ 65 years.
• HbA1c ≤ 8.5% (type 2 diabetic subjects).
• HbA1c ≤ 6.5% (obese and lean subjects).
• BMI ≥ 28 Kg/M^2 (Obese subjects with and without type 2 diabetes).
• BMI ≤ 25 Kg/M^2 (Lean subjects without type 2 diabetes).
• Use of sulfonylureas or metformin only (type 2 diabetec subjects).
• For female subjects: negative pregnancy test at the time of enrollment or study.
• No history of prior upper abdominal surgery such as adjustable gastric banding, pyloroplasty and vagotomy.
• No active systemic illness or malignancy.
• No symptomatic macrovascular or microvascular disease.
• No contraindications to MRI (e.g., metal implants, claustrophobia).
• Hematocrit > 35%.
• TSH > 0.4 or < 5.5.
• Consumption of < 2 alcohol drinks per day or < 14 per week or a negative AUDIT questionnaire.

Exclusion Criteria
•Obese Subjects with Type 2 Diabetes:

• Age ≤ 25 or ≥ 65 years (to avoid studying subjects who could have latent type 1 diabetes, or the effects of age extremes in subjects with normal or impaired fasting glucose).
• HbA1c ≥ 8.5%.
• BMI ≤ 28 Kg/M^2.
• Use of insulin or agents other than sulfonylureas or metformin.
• For female subjects: positive pregnancy test at the time of enrollment or study.
• History of prior upper abdominal surgery such as adjustable gastric banding, pyloroplasty and vagotomy.
• Active systemic illness or malignancy.
• Symptomatic macrovascular or microvascular disease.
• Contraindications to MRI (e.g., metal implants, claustrophobia).
• Hematocrit < 35%.
• TSH < 0.4 or > 5.5.
• Consumption of > 2 alcohol drinks per day or > 14 per week or a positive AUDIT questionnaire.

Inclusion Criteria
•Obese Subjects without Type 2 Diabetes:

• BMI ≥ 28 Kg/M^2.
• > 5% liver fat content, as determined by MRI using the proton density fat fraction (PDFF) technique.

Exclusion Criteria
•Obese Subjects without Type 2 Diabetes:

• Age ≤ 25 or ≥ 65 years (match subjects with T2DM).
• HbA1c ≥ 6.5%.
• BMI ≤ 28 Kg/M^2.
• Use of any glucose-lowering agents including metformin or sulfonylureas.
• For female subjects: positive pregnancy test at the time of enrollment or study.
• History of prior upper abdominal surgery such as adjustable gastric banding, pyloroplasty and vagotomy.
• Active systemic illness or malignancy.
• Symptomatic macrovascular or microvascular disease.
• Contraindications to MRI (e.g., metal implants, claustrophobia).
• Hematocrit < 35%.
• TSH < 0.4 or > 5.5.
• Consumption of > 2 alcohol drinks per day or > 14 per week or a positive AUDIT questionnaire.

Inclusion Criteria - Lean Subjects without Diabetes:

• Age ≥ 25 or ≤ 65 years (match subjects with T2DM).
• BMI ≤ 25 Kg/M^2). 

Exclusion Criteria
•Lean Subjects without Diabetes:

• Age ≤ 25 or ≥ 65 years (match subjects with T2DM).
• HbA1c ≥ 6.5%.
• BMI ≥ 25 Kg/M^2.
• Use of any glucose-lowering agents including metformin or sulfonylureas.
• For female subjects: positive pregnancy test at the time of enrollment or study.
• History of prior upper abdominal surgery such as adjustable gastric banding, pyloroplasty and vagotomy.
• Active systemic illness or malignancy.
• Symptomatic macrovascular or microvascular disease.
• Contraindications to MRI (e.g., metal implants, claustrophobia).
• Hematocrit < 35%.
• TSH < 0.4 or > 5.5.
• Consumption of > 2 alcohol drinks per day or > 14 per week or a positive AUDIT questionnaire.
• Liver fat content ≥ 5% as determined by MRI using the proton density fat fraction (PDFF) technique.

Eligibility last updated 1/12/22. Questions regarding updates should be directed to the study team contact.

• Patients with a diagnosis of soft tissue sarcoma.

• Unable or unwilling to provide informed consent

Eligibility last updated 1/12/22. Questions regarding updates should be directed to the study team contact.

• The individual must have received an infusion of gene-modified cells in a completed Kite-sponsored parent study, has not withdrawn full consent, and has discontinued or completed the post-treatment follow-up period in the parent study, as applicable.
• The individual must understand and voluntarily sign an Informed Consent Form (ICF) or an Informed Assent Form prior to any study-related assessments or procedures being conducted.
• In the investigator's judgment, the individual is willing and able to complete the protocol-required follow-up schedule and comply with the study requirements for participation.

• None.

Eligibility last updated 1/12/22. Questions regarding updates should be directed to the study team contact.

Inclusion Criteria

• Age ≥ 18 years.
• Histological confirmation of AL amyloidosis with adequate typing (mass spectrometry, immunohistochemistry, immunofluorescence, immunogold).
• AL amyloidosis with organ disease requiring therapy NOTE: There are no limitations in baseline measurable disease parameters.
• Patients must have monoclonal protein studies (serum free light chain assay, serum immunofixation or serum MASS-FIX) obtained at time of diagnosis before induction therapy initiated and available for review to be enrolled. Patients are allowed to participate in this study if urine electrophoresis immunofixation study was not done at time of diagnosis or cannot be obtained.
• Patients must achievement a hematological CR (irrespective of organ response achievement) or hematological VGPR (irrespective of organ response achievement) or hematological PR with at least one organ response after receiving Dara-CyBorD-based induction. For patients not assessable for hematological response (i.e., baseline dFLC < 50 mg/L), must achieve hematological CR, or dFLC < 10 mg/L or achieved organ response prior to randomization.
• Study allows to enroll patients in whom bortezomib and/or cyclophosphamide were omitted from induction due to toxicity concerns or adverse effects. Patients must receive at least daratumumab and dexamethasone at induction to qualify for the study.
• ECOG Performance Status (PS) 0, 1, 2 or 3.
• The following laboratory values obtained ≤ 28 days prior to registration:
  • Hemoglobin ≥ 8.0 g/dL;
  • Absolute neutrophil count (ANC) ≥ 1000/mm^3;
  • Platelet count ≥ 50,000/mm^3.
• Negative pregnancy test done ≤ 7 days prior to registration, for persons of childbearing potential only:
  • NOTE: If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
• Provide written informed consent.
• Ability to complete questionnaire(s) by themselves or with assistance.
• Willing to return to enrolling institution for follow-up (during the Active Monitoring Phase of the study).

Exclusion Criteria 

• Any of the following because this study involves an agent that has possible genotoxic, mutagenic and teratogenic effects:
  • Pregnant person;
  • Nursing person;
  • Persons of childbearing potential {and persons able to father a child} who are unwilling to employ adequate contraception.
• Multiple myeloma at time of diagnosis as defined by any of the following:
• • Hypercalcemia: Serum calcium > 1 mg/dL higher than upper limit of normal or > 11 mg/dL;
  • Renal insufficiency: Creatinine clearance < 40 mL per min or serum creatinine > 2 mg/dL attributed to high circulating light chains (i.e., cast nephropathy) or hypercalcemia;
  • Anemia: Hemoglobin > 2 g/dL below lower limit of normal, or < 10 g/dL, attributed to high marrow myeloma infiltration;
  • Bone lesions: ≥ 1 osteolytic lesion on skeletal x-ray, CT, or PET-CT (bone imaging is not mandatory but based on clinical suspicion);
  • Clonal bone marrow plasma cells ≥ 60%;
  • >1 focal lesion on MRI (MRI is not mandatory but based on clinical suspicion);
    • If bone imaging (CT, MRI, PET-CT) was not done at time of diagnosis it is not needed to be performed at registration to rule out bone disease;
    • ≥ 40% BMPCs irrespective of the above.
  • The study will allow patients with Involved: uninvolved sFLC ratio ≥ 100 if this is the only criteria that defines multiple myeloma if all the above criteria are not met.
• Immunocompromised patients and patients known to be HIV positive and currently receiving antiretroviral therapy:
  • NOTE: Patients known to be HIV positive, but without clinical evidence of an immunocompromised state, are eligible for this trial.
• Uncontrolled intercurrent illness including, but not limited to:
  • ongoing or active infection.
  • unstable angina pectoris.
  • psychiatric illness/social situations that would limit compliance with study requirements.

Note: Other protocol defined Inclusion/Exclusion Criteria may apply.

Eligibility last updated 10/20/22. Questions regarding updates should be directed to the study team contact.

• Diagnosis of PAH, confirmed by right heart catheterization (mean pulmonary artery pressure of 20 mmHg or greater, pulmonary vascular resistance of 3.0 Woods units or greater, Pulmonary capillary wedge pressure of 15 mmHg or lower).  
• Age ≥ 18 years.
• On PAH-specific therapy which is at stable dosing (i.e., not currently titrating therapy).
• NYHA class II-III symptoms.
• able to complete a six-minute walk test.

• Patients experiencing syncope or exertional syncope.
• Patients not experiencing exertional dyspnea.
• Inability to walk.
• Patients currently in pulmonary rehab or having completed pulmonary rehab within three months (unlikely to improve).

Eligibility last updated 3/14/22. Questions regarding updates should be directed to the study team contact.

- History of myelodysplastic syndrome (MDS) or AML

- History of another cancer within 3 years before Day 1 of study treatment, with the
exception of basal or squamous cell carcinoma of the skin that has been definitively
treated. A history of other malignancies with a low risk of recurrence, including
appropriately treated ductal carcinoma in situ (DCIS) of the breast and prostate
cancer with a Gleason score less than or equal to 6, are also not excluded

- If female, is pregnant or breastfeeding

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Eligibility last updated 8/23/22. Questions regarding updates should be directed to the study team contact.

• Patients undergoing percutaneous nephrolithotomy at Mayo Clinic Rochester.
• Adults ≥ 18 years old.
• Ability to receive and respond to electronic text messages.

• Unable or unwilling to provide informed consent.
• Patients who require Intensive Care Unit admission after surgery.
• Patients who have Clavien grade III or greater postoperative complications requiring additional intervention < 30 days after index procedure.

Eligibility last updated 1/17/22. Questions regarding updates should be directed to the study team contact.

• Male or female adults (≥ 18 years old).
• Frequent premature ventricular complexes or documented episode(s) of sustained VT, or evidence of appropriate ICD therapy in patients already implanted with ICDs.
• Structural heart disease, defined as impairment of left ventricular ejection fraction on echocardiography or MRI and/or presence of structural abnormality on imaging (myocardial late gadolinium enhancement on MRI, myocardial wall thinning, hypodensity or calcification on MDCT), and/or borderline, possible or definite diagnosis of arrhythmogenic right ventricular cardiomyopathy according to modified Task Force criteria.

• Contraindications to VT/PVC catheter ablation:
  • Current intra-cardiac thrombus;
  • Unstable angina and other acute or reversible cause;
  • Current or anticipated participation in any other clinical trial of a drug, device or biologic.
• Unwillingness to undergo CT and/or MRI imaging.

Eligibility last updated 1/21/22. Questions regarding updates should be directed to the study team contact.

Inclusion Criteria
•Patients:

• Adults ≥ 18 years
• Appointment to discuss osteoporosis management

Exclusion Criteria
•Patients:

• Major barriers to providing informed consent (i.e. dementia, severe hearing or visual impairment)

Inclusion Criteria
•Clinicians:

• Clinicians who meet with patients to discuss osteoporosis management.

Exclusion Critieria
•Clinicians:

• None

Inclusion Critieria
•PAG Members:

• Adults ≥ 18 years
• Member of the Knowledge and Evaluation Research (KER) Unit Patient Advisory Group (PAG)

Eligibility last updated 1/18/22. Questions regarding updates should be directed to the study team contact.

Subjects are eligible to be randomized in the study only if all of the following inclusion criteria and none of the exclusion criteria apply. To mirror the STEP-HFpEF trials CAMEO-SEMA will utilize essentially the same entry criteria, except for an EF cutoff. CAMEO-SEMA will use an EF value of ≥ 50% (rather than ≥ 45%) to define HFpEF, to harmonize with the recently published universal definition of HFpEF.59.

• Informed consent obtained before any trial-related activities. Trial-related activities are any procedures that are carried out as part of the trial, including activities to determine suitability for the trial.
• Age ≥ 18 years at the time of signing informed consent.
• BMI ≥ 30.0 kg/m^2.
• NYHA Class II-IV.
• LVEF ≥ 50 % within the preceding year.
• No hospitalizations due to heart failure in the preceding 30 days.
• At least one of the following:
  • Mean PCWP ≥ 15 mmHg or left ventricular end diastolic pressure (LVEDP) ≥ 15 mmHg documented during catheterization at rest, or PCWP or LVEDP ≥ 25 mmHg documented during catheterization at exercise;
  • If BMI < 35.0: NT-proBNP ≥ 220 pg/mL (for patients with sinus rhythm) or NT-proBNP ≥ 660 pg/mL (for patients with persistent/permanent atrial fibrillation); if BMI ≥ 35.0: NT-proBNP ≥ 125 pg/mL (for patients in sinus rhythm) or NT-proBNP ≥ 375 pg/mL (for patients with persistent/ permanent atrial fibrillation) at screening (NT-proBNP analyzed by the central laboratory) in combination with at least one of the following (documented by echocardiography within 12 months prior to or at screening):
    • Septal é < 7 cm/sec or lateral é < 10 cm/sec or average E/é ≥ 15;
    • PA systolic pressure > 35 mmHg;
    • Left atrial (LA) enlargement (LA width ≥ 3.8 cm or LA length ≥ 5.0 cm or LA area ≥ 20.0 cm^2 or LA volume ≥ 55 mL or LA volume index ≥ 29 mL/m^2);
    • LV hypertrophy with septal thickness or posterior wall thickness ≥ 1.2 cm.
  • Hospitalization with a primary diagnosis of decompensated heart failure which required intravenous (IV) loop diuretic treatment, within the previous 12 months in combination with at least two of the following (documented by echocardiography within 12 months prior to or at screening):
    • Septal é < 7 cm/sec or lateral é < 10 cm/sec or average E/é ≥ 15;
    • PA systolic pressure > 35 mmHg;
    •  
    • LA enlargement (LA width ≥ 3.8 cm or LA length ≥  5.0 cm or LA area ≥ 20.0 cm^2 or LA volume ≥ 55 mL or LA volume index ≥ 29 mL/m^2);
    • LV hypertrophy with septal thickness or posterior wall thickness ≥ 1.2 cm;
    • Ongoing use of diuretic therapy for at least 30 days prior to screening.

Cardiovascular-related:

• Myocardial infarction, stroke, hospitalization for heart failure, unstable angina pectoris or transient ischemic attack within 30 days prior to the day of screening.
• Systolic blood pressure > 160 mmHg at screening.
• Planned coronary, carotid or peripheral artery revascularization.
• Any other condition judged by the investigator to be the primary cause of dyspnea (such as heart failure due to restrictive cardiomyopathy or infiltrative conditions (e.g., amyloidosis), hypertrophic obstructive cardiomyopathy, primary pulmonary arterial hypertension, chronic obstructive pulmonary disease, right heart failure due to pulmonary disease, complex congenital heart disease, anemia, or more than moderate heart valve disease).
  • Amyloid cardiomyopathy may be present in 5-15% of patients presenting with the clinical syndrome of HFpEF,60-62 and patients with amyloid may respond differently to WL intervention. To enhance the scientific rigor of the trial by ensuring a homogenous population of true primary HFpEF, we will carefully evaluate for the presence of amyloid using the approach outlined in a recent scientific statement from the AHA,63 which is also consistent with our current clinical practice.
• Specifically, potential participants will be evaluated for clues or risk factors for underlying cardiac amyloid including intolerance to antihypertensives, hypotension, orthostatic intolerance, persistent low-grade elevation in troponin, low QRS voltage on ECG, unexplained AV block or prior pacemaker, unexplained LV or RV wall thickening, impaired LV global longitudinal strain with apical sparing by echocardiography, family history of cardiomyopathy, neuropathy, autonomic dysfunction, carpal tunnel syndrome,  lumbar spinal stenosis, family history of polyneuropathy, or black race. Patients with these risk factors will undergo screening evaluation for amyloid prior to consent in CAMEO-SEMA as part of best clinical practice.  This includes screening for monoclonal light chain as first step, followed by hematology consultation if the screen is positive.  Patients with risk factors but no monoclonal light chain will then undergo Tc-99m-PYP scan to rule out cardiac amyloid.

Obesity-related:

• Bariatric surgery prior to screening or planned bariatric surgery within the trial time course.
• A self-reported change in body weight > 5 kg (11 lbs) within 90 days before screening irrespective of medical records.

Glycemia-related:

• HbA1c ≥ 6.5% based on latest available value from medical records, no older than 3 months or if unavailable at local measurement at screening.
• History of type 1 or type 2 diabetes (history of gestational diabetes is allowed).
• Treatment with any GLP-1 receptor agonist within 90 days prior to the day of screening.

General health and safety:

• Personal or first-degree relative(s) history of multiple endocrine neoplasia type 2 or medullary thyroid carcinoma.
• Presence of acute pancreatitis within the last 180 days prior to screening.
• History or presence of chronic pancreatitis.
• End-stage renal disease or chronic or intermittent hemodialysis or peritoneal dialysis.
• Presence or history of malignant neoplasm within 5 years prior to the day of screening. Basal and squamous cell cancer and any carcinoma in-situ are allowed.
• Known or suspected hypersensitivity to trial product(s) or related products.
• Participation in any clinical trial of an approved or non-approved device for the treatment of heart failure or obesity within 30 days before screening.
• Receipt of any investigational medicinal product within 30 days before screening.
• Female who is pregnant, breast-feeding or intends to become pregnant or is of child-bearing potential and not using a highly effective contraceptive method.
• Major surgery scheduled for the duration of the trial, affecting walking ability in the opinion of the investigator.
• Any disorder, including severe psychiatric disorder, suicidal behavior within 90 days before screening, and suspected drug abuse, which in the investigator´s opinion might jeopardize subject´s safety or compliance with the protocol.
• The criteria will be assessed at the investigator’s discretion unless otherwise stated.

Eligibility last updated 1/17/22. Questions regarding updates should be directed to the study team contact.

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Eligibility last updated 4/11/23. Questions regarding updates should be directed to the study team contact.