Inclusion Criteria
•Challenge Study:  

• Males or females 18 to 70 years of age, inclusive.
• Subjects demonstrate willingness to participate in the study and to perform all required procedures as documented by signed informed consent.
• Subjects must have a diagnosis of celiac disease CeD by intestinal biopsy at least 12 months and positive celiac serology at some point in their evaluation, prior to screening as confirmed by medical records or written physician statement.
• Subjects must have reported following a strict GFD for at least the 12 consecutive months and must be willing to maintain their current diet for the duration of study participation while being in gluten challenge.
• Patients who don’t show mucosal healing with a VH:CD ratio < 2 at the baseline endoscopy will enter the GFD non-healed cohort (see below) and will not undergo gluten challenge.   Ninety percent of patients who are asymptomatic, adhere to GFD and are seronegative have achieved histologic healing.

Exclusion Criteria
•Challenge Study:

• Current diagnosis of any severe complication of CeD, such as refractory CeD (RCD) type I or II, enteropathy-associated T-cell lymphoma (EATL), ulcerative jejunitis, or GI perforation.
• Diagnosis of any chronic, active GI disease other than CeD, such as active, untreated peptic ulcer, eosinophilic esophagitis, erosive esophagitis , ulcerative colitis or Crohn’s disease, microscopic colitis, irritable bowel syndrome, small intestinal bacterial overgrowth, tropical sprue, or other GI and non-GI disorder or prior GI surgery that may, in the Investigator’s opinion, interfere with the assessment of symptoms of abdominal pain, diarrhea, or other components of CeD.
• Selective IgA deficiency, defined as having undetectable levels of serum IgA.
• History of severe reaction to gluten exposure that is considered incapacitating or life-threatening.
• Known or suspected exposure to COVID-19 infection in the 4 weeks before the screening.
• History or presence of any clinically significant disease that, in the opinion of the Investigator may confound the subject’s participation and follow-up in the clinical trial or put the subject at unnecessary risk, including but not limited to: uncontrolled hypertension (BP ≥180/110 mm/Hg), unstable angina, Class II congestive heart failure or major fluid overload, coronary angioplasty or myocardial infarction within the past 6 months, clinically significant arrhythmias or electrocardiogram (ECG) abnormalities, severe chronic pulmonary disease, or any renal, hematologic, GI, immunologic, dermatologic, neurologic, or psychiatric disease.
• History of significant substance or alcohol abuse during the 12 months prior to screening as obtained by medical record and/or subject report.
• Females who are pregnant or planning to become pregnant during the study period, or who are currently breastfeeding.
• Participation in another investigational drug or device study or treatment with an investigational drug within 30 days or 5 half-lives, whichever is longer, prior to screening.
• Individuals with uncontrolled clotting disorders or on anti-coagulants that they can’t safely hold prior to endoscopy.
• Participation in clinical trial within 30 days prior to consenting, and 12 months for a clinical trial including a biologic agent.
• Participation in clinical trial with tolerogenic agents.

Inclusion Criteria
•De-challenge Study:

• Males or females, 18 to 70 years of age, inclusive.
• Subjects demonstrate willingness to participate in the study and to perform all required procedures as documented by signed informed consent.
• Newly suspected subjects of CeD, either typical symptoms of CeD or referred to celiac clinic due to positive CeD serology undergoing upper endoscopy. Patients with weak positive serology will not be included in order to maximize the likelihood of the patients qualifying for the dechallenge study.    
• Subjects who are currently not on GFD.

Exclusion Criteria
•De-challenge Study:

• Has a history of chronic inflammatory gastrointestinal disease (example, inflammatory bowel disease, extensive colitis, ulcerative jejunitis, drug induced enteropathy) (Microscopic colitis is not an exclusion criteria).
• Has chronic infectious gastrointestinal illness, or acute infectious gastrointestinal illness within the 4-week period prior to screening.
• Known history of lymphoproliferative disease, including monoclonal gammopathy of unknown significance, lymphoma, or signs and symptoms suggestive of possible lymphoproliferative disease, such as lymphadenopathy and/or splenomegaly.
• Individuals with uncontrolled clotting disorders or on anti-coagulants that they can’t safely hold prior to endoscopy.
• Known or suspected exposure to COVID-19 infection in the 4 weeks before the screening.
• History or presence of any clinically significant disease that, in the opinion of the Investigator may confound the subject’s participation and follow-up in the clinical trial or put the subject at unnecessary risk, including but not limited to: uncontrolled hypertension, unstable angina, Class II congestive heart failure or major fluid overload, coronary angioplasty or myocardial infarction within the past 6 months, clinically significant arrhythmias or ECG abnormalities, severe chronic pulmonary disease, or any renal, hematologic, GI, immunologic, dermatologic, neurologic, or psychiatric disease.
• History of significant substance or alcohol abuse during the 12 months prior to screening as obtained by medical record and/or subject report.
• Participation in another investigational drug or device study or treatment with an investigational drug within 30 days or 5 half-lives, whichever is longer, prior to screening.
• Participation in clinical trial within 30 days prior to consenting, and 12 months for a clinical trial including a biologic agent.
• Participation in clinical trial with tolerogenic agents
• Participants whose initial biopsies do not reveal villous atrophy will not be followed in the de-challenge group but may be recruited into the potential celiac disease cross sectional group so long as they meet the criteria for inclusion into that group.

Inclusion Criteria
•Controls:

• Subjects (both cases and controls) will include males and non-pregnant females, aged 18-70 years.
• Females of reproductive age or capacity (i.e. not having had tubal ligation or sterilization) will have a pregnancy test performed.

Exclusion Criteria
•Controls:

• Subjects on antibiotics, proton pump inhibitors, aspirin, non-steroidal anti-inflammatory drugs, alcohol intake within 48 hours, a bowel preparation within 4 weeks of the studies, and smokers
• Subjects will be asked not to take any probiotics in the week before testing.
• Any known intestinal inflammation such as GERD, eosinophilic esophagitis, and inflammatory bowel disease.
• Prior gastrointestinal surgery (other than appendectomy)
• Ongoing use of antiplatelet agents or anticoagulants.
• Controls should not have a prior history of or family history of CD.
• Subjects unable to provide informed consent
• The presence of any medical or psychological condition could interfere with the safe performance of the upper endoscopy.

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

Eligibility last updated 9/19/23. Questions regarding updates should be directed to the study team contact.

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

Eligibility last updated 10/25/22. Questions regarding updates should be directed to the study team contact.

• BMI 30-50 kg/m^2 for at least 6 months prior to ESG.
• Ages 22-69.
• Diagnosis of UC with plans to undergo or who have already undergone colectomy as part of a plan to pursue eventual 3-stage ileal pouch anal anastomosis (IPAA).
• Willing to adhere to the diet and behavior modifications required for ESG.
• Able to follow the visit schedule.
• Able to provide informed consent.

• Prior gastric or bariatric surgery or other alteration to upper gastrointestinal anatomy which would preclude safe or technical performance of ESG.
• Current or recent (last six months) gastric or duodenal ulceration.
• Esophageal or gastric varices.
• Significant motility disorder of the esophagus or stomach.
• Large hiatal hernia measuring > 5 cm or ≤ 5 cm and associated with severe gastroesophageal reflux.
• Severe coagulopathy, hepatic insufficiency, or cirrhosis.
• Gastric mass.
• Presence of any other medical condition which precludes safe performance of elective endoscopy such as poor general health and/or history of severe hepatic, cardiac, or pulmonary disease.
• Serious or uncontrolled psychiatric illness which may compromise patient understanding of procedure or compliance with follow-up visits.
• Unwilling to participate in an established diet and behavior modification program, with routine follow-up.
• Ongoing corticosteroid use at a dose of > 5 mg daily.
• Daily use of anti-inflammatory agents such as non-steroidal medications, or anticoagulants without medical supervision.
• Alcohol or drug addiction.
• Females who are pregnant, nursing, or planning pregnancy within the next year.
• Concomitant use of or unwillingness to avoid any use of weight loss medications, weight loss supplements, or weight loss herbal preparations.
• Has a condition or is in a situation which in the investigator's opinion may put the subject at significant risk or may interfere significantly with the subject's participation in the study.

Eligibility last updated 8/26/22. Questions regarding updates should be directed to the study team contact.

• Between 50 and 75 years of age, inclusive.
• Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
• Patient must not have acute pancreatitis or a history of chronic pancreatitis.
• Patient must have received a computed tomography (CT) or magnetic resonance imaging (MRI) within 3 months of registration that revealed a newly identified ≥ 1 cm pancreatic cyst.
• Women of childbearing potential must not be known to be pregnant.
• Patient must not have a prior diagnosis of pancreatic cyst or pancreatic malignancy of any type.
• Patient must not have a history of pancreatic resection.
• Patient must not have other asymptomatic pancreatic cystic lesion with zero/low malignancy potential (pancreatic pseudocyst, classic serous cystic lesion) on index CT or MRI.
• Patient must not have a family history of pancreatic adenocarcinoma in 1 or more first degree relatives.
• Patient must not have pancreatic cyst morphology that would prompt immediate surgical consideration (enhancing mural nodule, solid component in cyst, pancreatic duct > 10 mm, cyst causing obstructive jaundice).
• Patient must not have a comorbid illness that precludes pancreatic cyst resection.
• Patient must not be participating in an already established surveillance program.

• Under 50 or over 75 years of age.

Inclusion Criteria

• Age ≥ 18 years.
• History of breast Cancer, ER+, Her 2 positive or negative.
• Fatigue ≥ 4/10.
• Currently taking any aromatase inhibitor in the curative setting and planning to be on such for at least 8 weeks after registration. (Patients on concurrent ovarian suppression (such as with leuprolide acetate, goserelin) are allowed).
• Prior treatment: last chemotherapy ≥ 90 days prior to randomization (if treated with chemotherapy). 
• On a stable dose of pain medications if pain medications are being regularly used. (i.e., no change in dosage in the past 30 days).
• If on supplements, must be on stable dose with no plan to change; not on or planning any acupuncture or other specific supportive modalities for fatigue or AI arthralgias.
• ECOG Performance Status (PS) 0, 1 or 2.
• Required Initial laboratory values obtained ≤ 30 days prior to randomization, including the following:
• • White blood cell count (WBC) ≥ 3,000/mm^3;
  • Hemoglobin ≥ 10 g/dL;
  • Platelet count ≥ 100,000/mm^3;
  • Total bilirubin ≤ 1.5 x ULN;
  • Alanine aminotransferase (ALT) or Aspartate transaminase (AST) ≤ 1.2 x ULN;
  • PT/aPTT ≤ 1.5 x ULN.
• Negative pregnancy test done ≤ 7 days prior to registration, for persons of childbearing potential only.
• Provide written informed consent.
• Ability to complete questionnaires.
• Willing to return to enrolling institution during the Active Monitoring Phase of the study.

• Other known uncontrolled medical conditions causing fatigue such as untreated thyroid disease, depression, fibromyalgia, chronic fatigue syndrome, infection, autoimmune disease, or active/untreated hepatitis.
• Allergy to mushrooms.
• On anticoagulation medication or aspirin or having a known bleeding disorder.
• On any specific medication for fatigue (e.g., methylphenidate).
• Metastatic cancer diagnosis (history of nodal metastases is allowed).
• Chronic steroid use, unless on physiologic replacement doses.
• Current use of any medical mushrooms.
• On medications for diabetes.
• History of symptomatic hypotension.
• Taking CYP3A4, CYP2D6 or CYP2E1 substrates.
• Taking CDK4/6 inhibitors or olaparib.
• Any of the following because this study involves an agent that has unknown genotoxic, mutagenic and teratogenic effects:
  • Pregnant persons;
  • Nursing persons;
  • Persons of childbearing potential who are unwilling to employ adequate contraception.

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

Eligibility last updated 6/30/23. Questions regarding updates should be directed to the study team contact.

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

Eligibility last updated 6/19/23. Questions regarding updates should be directed to the study team contact.

• ≥ 50 years of age.
• Diagnosis of GCA by confirmation of temporal artery biopsy and/or advanced arterial imaging (CT angiogram, MR angiogram, PET-CT) consistent with large vessel vasculitis.
• Treated with tocilizumab (subcutaneous OR intravenous) for ≥ 12 months but < 48 months prior to study entry.
• In clinical remission (that is no symptoms present to suggest active GCA) at study entry.
• Off prednisone or its equivalent for minimum 2 months prior to study entry.
• Access to a computer or smartphone/device.

• Uncontrolled diabetes with inability to control glucose level below 200 mg/dl (requirement for obtaining PET-CT).
• Features of active GCA.
• Treatment of tocilizumab for other etiologic reason (besides GCA) for which continuation of tocilizumab is deemed necessary (e.g., concomitant rheumatoid arthritis).
• Ring size smaller than 6 or larger than 13 on digits 2 or 3 (index or middle, respectively).
• Current (other than non-melanoma skin cancer) malignancy or active infection.

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

Eligibility last updated 11/30/22. Questions regarding updates should be directed to the study team contact.

• Patients ages 18 and older (no upper age limited defined).
• Patients with well-classified essential tremor, who are already receiving regular DBS therapy at Mayo Clinic for their movement disorder.
• Ability to understand study procedures and to comply with them for the entire length of the study and use study devices as outlined in protocol. 
• Patient agrees to perform daily tasks in BrainRISE app and consents to the study collecting video and audio recordings during those tasks. 
• Proficient in the use of a smart phone.

• Cognitive or psychiatric condition rendering a patient unable to cooperate with data collection, or to manage and recharge smart watch and tablet computer devices. Presence of open or healing wounds near monitoring sites (infection risk).
• Inability or unwillingness of individual or legal guardian/representative to give written informed consent.

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

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

Inclusion Citeria:

• Followed by pediatric hematology/oncology.
• Receiving recombinant Erwinia asparaginase for treatment of malignancy.

• Patients < 1 year of age.
• Patients who have previously received recombinant Erwinia asparaginase within the past two weeks.

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

Eligibility last updated 6/27/23. Questions regarding updates should be directed to the study team contact.

• ≥ 18  years old.
• Diagnosed with PD.
  • Palpable penile plaque.
  • Dorsal, lateral, or dorsolateral penile curvature.
  • Penile curvature > 30 degrees and < 90 degrees as measured using goniometer during objective curvature assessment.
  • Non-calcified plaque or grade 1 calcification (“stippling”, no shadowing) as determined by penile duplex Doppler ultrasound (PDDU).
  • “Stable PD symptoms":
    • PD symptom duration > 6-months;
    • Stable symptoms > 3-months.
• Patient undergoing intralesional CCH for PD.

• Prior intralesional injections or surgery for PD.
• Severe baseline penile pain.
• Moderate or severe baseline ED based on IIEF-EF domain.
• History of low intensity shockwave therapy for sexual dysfunction (ED or PD).
• Ventral or ventrolateral penile curvature.
• Moderate or severe (grade 2/3) plaque calcification as determined by PDDU.
• Inability to achieve satisfactory erection rigidity at time of baseline curvature assessment.

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

Eligibility last updated 3/7/23. Questions regarding updates should be directed to the study team contact.

• Age ≥ 18 years.
• Histological confirmation of primary breast cancer.
• Patients with metastatic breast cancer and at least 12 months of clinical response to first-line systemic therapy, with the subsequent development of 1-3 extracranial sites of oligoprogressive disease.
  • NOTE: patients with de novo metastatic disease and those developed metastatic disease after initially localized disease can both be included; OR
• Patients with metastatic breast cancer and at least 6 months of clinical response to second-line systemic therapy (or further, e.g., third- or fourthline), with the subsequent development of 1-3 extracranial sites of oligoprogressive disease.
• ECOG Performance Status (PS) ≤ 2).
• Negative urine or serum pregnancy test done ≤ 7 days prior to registration, for women of childbearing potential only.
• Ability to complete questionnaire(s) by themselves or with assistance.
• Provide written informed consent.
• Willing to return to enrolling institution for follow-up (during the Active Monitoring Phase of the study).
• Willing to provide blood samples for correlative research purposes.
• Receiving radiation therapy as specified in the protocol.

• Male patients.
• Nursing or pregnant women.
• Men or women of childbearing potential who are unwilling to employ adequate contraception.
• Patients with triple negative disease (negative for ER, PR, and HER2). Patients with ER negative, PR positive, and HER2 negative disease will also be excluded.
• Active second primary malignancy.
• > 3 extracranial sites of oligoprogressive disease.
• Active CNS disease. Patients with asymptomatic and stable, treated CNS lesions (radiation and/or surgery and/or other CNSdirected therapy who have not received corticosteroids for at least 4 weeks) are allowed.
• Active connective tissue disease that is felt by the treatment team to pose an excess risk of toxicity.
• Prior radiation that overlaps with the intended treatment volume such that, in the opinion of the patient’s Radiation Oncologist, radiotherapy to progressing sites will not be safe.
  • NOTE: patients with some dose overlap with prior radiotherapy that is deemed safe by the patient’s Radiation Oncologist can be included in the trial.

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

Eligibility last updated 8/15/23. Questions regarding updates should be directed to the study team contact.

• Patients with physician-diagnosed CRSwNP, with or without comorbid asthma that meet indication criteria for FDA-approved use of Dupixent.
• Patients aged 18 years and older.
• Patient willing to provide consent to be a participant in the study.
• Patients with insurance that allows Dupixent coverage or Dupixent coverage obtained through Dupixent MyWay Program.

• Age under 18.
• Suspected or diagnosed allergic fungal rhinosinusitis.
• Suspected or diagnosed cystic fibrosis.
• Dupixent coverage denied through insurance or Dupixent MyWay Program.
• Patients who required a steroid taper in the preceding 30 days. However, patients on chronic steroids equal to ≤ 20 mg of prednisone daily, are eligible.
• Patients who were on a different biologic medication in the preceding 3 months.
• Patients with a diagnosis of EGPA/Churg-Strauss Sydnrome.
• Pregnant patients.
• Patients with inverted papilloma growth.

1. Age ≥ 18 ≤ 70 years.

2. Definite NASH on a liver biopsy obtained ≤ 90 days prior to randomization with a NAFLD activity score (NAS) of ≥ 4 with at least 1 in each component of the NAS according to NASH CRN grading52.

3. Fibrosis stage ≥ 2 as assessed by liver biopsy.

4. Not currently on statin therapy.

5. Provision of written informed consent.

6. Agree to use of effective contraceptive measures if female of child bearing potential.

2. Cirrhosis, as assessed clinically or histologically.

3. Presence of vascular liver disease.

4. BMI ≤ 25 kg/m^2.

5. Excessive alcohol use (> 20 g/day) within the past 2 years.

6. AST or ALT > 250 U/L.

7. Type 1 diabetes mellitus.

8. Bariatric surgery in the past 5 years.

9. Weight gain of > 5% in past 6 months or > 10% change in past 12 months.

10. Inadequate venous access.

11. HIV antibody positive, hepatitis B surface antigen positive (HBsAg), or HCV
RNA positive.

12. Receiving an elemental diet or parenteral nutrition.

13. Chronic pancreatitis orpancreatic insufficiency.

14. Any history of complications of cirrhosis (i.e., ascites, hepatic encephalopathy, or portal hypertensive bleeding), even if absent or optimized
with medical management at time of screening.

15. Concurrent conditions:

a) Inflammatory bowel disease;

b) Unstable angina, myocardial infarction, transient ischemic events, or stroke within 24 weeks of screening;

c) Ongoing infectious, immune mediated disease within previously 1 years;

d) Any malignant disease (other than basal cell carcinoma of the skin) within previous 5 years;

e) Prior solid organ transplant;

f) Any other concurrent condition which, in the opinion of the investigator, could impact adversely on the subject participating or the interpretation of the study data.

16. Concurrent medications including:

1. Anti-NASH therapy(s) initiated after the liver biopsy diagnosing NASH. Anti-NASH
therapies include S-adenosyl methionine (SAMe), milk thistle, and vitamin E at
dose of ≥ 400 IU / day.

2. Antidiabetic mediation which may impact NASH histology started in the past 12
months including thiazolidinediones (glitazones), dipeptidyl peptidase 4
inhibitors (gliptins) or glucagon-like peptide 1 analogs.

3. Immune modulatory agents including systemic steroids, methotrexate, anti-TNF-?
therapies (infliximab, adalimumab, etanercept) or anti-integrin therapy
(namixilab).

17. Self-reported or known marijuana or illicit drug use 30 days before the
screening 18. The following laboratory abnormalities within 90 days of screening:

1. HbA1C > 9.0 %;

2. Neutrophil count < 1.0 x 10^9 / L;

3. Platelets < 100 10^9 / L;

4. Hemoglobin < 10 g/dl;

5. Albumin < 3.5 g;

6. Prolonged international normalized ratio (INR);

7. Any elevation of bilirubin above normal (unless Gilbert's syndrome or
extrahepatic source as denoted by increased indirect bilirubin fraction);

8. Serum creatinine > 1.5 mg/dl;

9. Creatinine clearance ≤ 50 ml/minute calculated by Crockroft-Gault or creatinine >
1.5 x upper limit of normal.

19. Pregnancy or breastfeeding.

20. Women, of childbearing age, who are not willing to practice effective contraception (i.e.,
barrier, oral contraceptives, or past medical history of hysterectomy) for the 48-week duration of the trial and for 1 month after the first administration of
the drug.

21. Participation in an investigational drug study within past 3 months.

Eligibility last updated 11/30/22. Questions regarding updates should be directed to the study team contact.

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

Eligibility last updated 10/20/23.  Questions regarding updates should be directed to the study team contact.

• Co-enrolled in the study titled “Clinical and Basic Investigations into Congenital Disorders of Glycosylation” at one of the clinical centers (IRB 19-005187).
• Genetically confirmed PMM2-CDG diagnosis.
• ≥ 2 years of age.

• Diagnosis of a second genetic disease.
• Individuals who have situations that would limit compliance with the study requirements.

• Age greater than 18 and able to provide consent.
• Diagnosis of fibrotic interstitial lung disease defined by the presence of greater than 10% fibrotic changes on CT imaging within 6 months of study enrollment.
• Any disease severity based on pulmonary function testing.
• Any treatment approach including steroids, immune modulators, and antifibrotic agents.
• Patient may be enrolled in other research studies.

• Less than 10% fibrosis on CT imaging.
• Cognitive or memory impairment with inability to complete questionnaires.

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

Eligibility last updated 7/28/23. Questions regarding updates should be directed to the study team contact.

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

Eligibility last updated 11/2/23. Questions regarding updates should be directed to the study team contact.

• Previously untreated active multiple myeloma starting a new treatment for their disease with one of the three established treatment regimens: VRd, DRd, or DVRd.
• No prior treatment for myeloma.
• Not receiving concurrent treatment for another active malignancy.
• No more than 3 months from start of treatment.

• < 18 years of age. 

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

Eligibility last updated 6/21/23. Questions regarding updates should be directed to the study team contact.

• Living kidney donors > 18 years.

• Anyone not meeting the inclusion criteria including liver donors.

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

Eligibility last updated 8/10/23. Questions regarding updates should be directed to the study team contact.

• Children under the age of 18.
• Presenting to the Emergency Department at Mayo Clinic/St. Marys as a leveled trauma activation for blunt trauma.
• Receiving blood draw for clinical labs.

• Patients who are known to be pregnant or prisoners.
• Patients whose injuries are the result of intentional self-harm.

• A definite diagnosis of hereditary hemorrhagic telangiectasia is defined as having at  least 3 of the following criteria:  
  • Spontaneous and recurrent epistaxis;
  • Multiple telangiectasias at characteristic sites: lips, oral cavity, fingers, nose;
  • Visceral lesions: GI telangiectasia, pulmonary, hepatic, cerebral or spinal AVMs.  
• A first degree relative with hereditary hemorrhagic telangiectasia according to these criteria OR a definite diagnosis of hereditary hemorrhagic telangiectasia is defined as having a gene sequencing diagnosis of hereditary hemorrhagic telangiectasia:
  • Epistaxis due to hereditary hemorrhagic telangiectasia at least 2 x per week, for a  cumulative duration of at least 25 minutes per week;
  • Epistaxis is clinically stable during the 12 weeks prior to screening in the clinical  judgment of the investigator (i.e., no major changes in frequency or duration of  epistaxis);
  • Participant agrees not to undergo cautery of nasal telangiectasias or take any experimental therapies for hereditary hemorrhagic telangiectasia other than the study drug while participating in the study.
• Male or female [non-child bearing potential].

• Participant has known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to pazopanib that in the opinion of the investigator contradicts their participation.
• Currently has untreated cerebral arterio-venous malformations (AVMs), cerebral  arteriovenous fistulae, or cerebral cavernous malformations (CCMs) (Note: MRI scan does not need to be repeated at screening if AVMs, arterio-venous fistulas and CCMs were absent on a scan at age ≥ 18 years).  
• Currently has perfused pulmonary AVMs with feeding artery diameter > 3mm.  
• Known significant bleeding sources other than nasal or gastrointestinal.
• Systemic use of a vascular endothelial growth factor inhibitor in the past 3 months or  previous enrollment in this study.
• Active and recent onset of clinically significant diarrhea.
• Current or recent (in the last 5 years) malignancies (except non-melanoma skin cancers).
• Participant has had major surgery (e.g., surgical ligation of an AVM) or trauma within 28 days or had minor surgical procedures (e.g., central venous access line removal)  within 7 days prior to dosing, the latter representing a recent wound, fracture or ulcer.
• Participant has a planned surgery during the period to include active treatment and 6 weeks of follow up.  
• Participant has clinically significant gastrointestinal abnormalities (other than  hereditary hemorrhagic telangiectasia related vascular lesions).
• Participant during the 6 months prior to first dose of study drug has a history of cerebrovascular accident (including transient ischemic attacks), pulmonary embolism, untreated deep vein thrombosis (DVT), myocardial infarction, or any other thrombotic event.
• QT corrected interval ≥ 450 msec, based on averaged QT corrected interval values of triplicate ECGs obtained over a brief recording period.
• Hemoglobin < 6 g/dL.
• Platelets < 100 x 10^9/L.  
• International normalized ratio (INR) >1.2 x upper limit of normal and activated partial  thromboplastin time (aPTT) > 1.2 x upper limit of normal.  
• Alanine Transaminase > 2 x upper limit of normal.
• Bilirubin > 1.5 x upper limit of normal (isolated bilirubin > 1.5 x upper limit of normal  is acceptable if bilirubin is fractionated and direct bilirubin < 35%).  
• Participant has poorly controlled hypertension [defined as systolic blood pressure  (SBP) ≥ 140 mmHg or diastolic blood pressure (DBP) ≥ 90 mmHg.  
• Substantive renal disease (eGFR < 30 mL/min/1.73m^2 calculated using the Cockcroft-Gault  formula).
• Echo derived left ventricular ejection fraction < 30%.
• Thyroid stimulating hormone > upper limit of normal.  
• Urine protein to creatinine ratio > 0.3.
• Neutrophil count < 1500/mm^3.

Eligibility last updated 10/5/21. Questions regarding updates should be directed to the study team contact.

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

Eligibility last updated 10/27/23. Questions regarding updates should be directed to the study team contact.

• ≥ 75+ years
• Part of National Patient-Centered Clinical Research Network (PCORnet) and the Veterans Affairs (VA) system.
• Enrolled in the PREVENTABLE trial.

• < 75 years of age. 

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

Eligibility last updated 5/25/23. Questions regarding updates should be directed to the study team contact.

​​​​​​

• [Phase 1b only] Subject is a male or female and is between the age of 18 to 65 years, inclusive, at screening.
• [Phase 1b only] Subject has had a documented pouchoscopy within 12 months prior to screening.
• [Phase 2 only] Subject is a male or female and is aged 18 years or older at screening.
• Subject or the subject's legally acceptable representative is willing and able to provide written informed consent prior to the initiation of any study-related procedures.
• Subject has had an IPAA for at least 6 months prior to screening.
• Subject has an average daily bowel movement frequency of at least 10 bowel movements recorded during screening and has correctly completed at least 7 days of electronic diary (eDiary) entries during the screening period.
• Female subjects of childbearing potential must have a negative serum pregnancy test result at screening and must not be lactating and/or breastfeeding.
• Female subjects of childbearing potential and male subjects with partners of childbearing potential must agree to use proper contraceptive methods to avoid pregnancy during the study.
• [Phase 2 OL extension only] Subject must have completed the Phase 2 double-blinded part of the study and be willing to participate in the optional open-label extension phase.
• [Phase 2 OL extension only] Subject must understand the study procedures, the risks involved, and be willing to continue to adhere to the study visit/protocol schedule.

• [Phase 1b only] Subject has Crohn's-like disease of the pouch, as indicated by their most recent pouchoscopy during the 12 months prior to screening.
• [Phase 1b only] Subject has a stricture of the IPAA or afferent limb stricture, as indicated by their most recent pouchoscopy during the 12 months prior to screening.
• [Phase 2 only] Subject has Crohn's-like disease of the pouch, as indicated by the pouchoscopy conducted during study screening.
• [Phase 2 only] Subject has isolated severe cuffitis without pouch inflammation (endoscopic modified Pouch Disease Activity Index (mPDAI) score of 2 or lower).
• [Phase 2 only] Subject has a stricture of the IPAA or afferent limb stricture as indicated by the pouchoscopy conducted during study screening.
• Subject has enterocutaneous or recto- or pouch-vaginal fistula.
• Subject has active Clostridium difficile infection.
• Subject has known or suspected active cytomegalovirus (CMV) infection.
• Subject initiated a new treatment with antibiotics or antimotility therapies within the 2 weeks prior to screening or plans to start a new or change doses of a current treatment during the study period.
• Subject has taken biologics, azathioprine, or methotrexate within the 12 weeks prior to screening or systemic steroids within 4 weeks of screening.
• Subject is taking NSAIDs as a long-term treatment (i.e., consistent use for at least 4 days/week each month).
• Subject has a known history or positive test during screening for HIV, HIV-1, HIV-2, or active hepatitis B virus (HBV) or hepatitis C virus (HCV).
• Subject has a positive reverse transcriptase-polymerase chain reaction (PCR) diagnostic test for SARS-CoV-2 (COVID-19) within the 14 days prior to screening.
• Subject has a history of malignancy within the 5 years prior to screening, with the exception of nonmelanoma skin cancer that has been treated with no evidence of recurrence, treated cervical dysplasia, or treated in situ grade 1 cervical cancer.
• Subject has estimated glomerular filtration rate <30 mL/min/1.73 m^2 at screening.
• Subject has uncontrolled hypertension at screening.
• Subject has known hypersensitivity to EXE-346 or any product components.
• Female subject is pregnant or lactating and/or breastfeeding.
• Subject has participated in any clinical study of an approved or unapproved investigational medicinal product within the 30 days prior to screening.
• Subject has any disorder that, in the investigator's opinion, might jeopardize the subject's safety or compliance with the protocol, including but not limited to:
  • Decompensated liver disease;
  • Elevation of aspartate aminotransferase (AST), alanine aminotransferase (ALT), or bilirubin >2 × upper limit of normal (ULN);
  • Primary sclerosing cholangitis with elevated transaminases.
• [Phase 2 OL extension only] Subject has developed any medical or psychologic condition excluded in the Phase 2 double-blinded part of the study or which, in the investigator's opinion, might create undue risk to the subject, interfere with the subject's ability to comply with the protocol requirements, or interfere with the subject's ability to complete the study.

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

Eligibility last updated 7/25/23. Questions regarding updates should be directed to the study team contact.

12. History of immunodeficiency diseases, including a positive HIV test result at
screening.

13. A positive hepatitis B surface antigen or hepatitis C test result at screening.

14. Subjects with known bleeding disorders, or who are under treatment with anticoagulants
or with a platelet count <50,000 (due to the increased risk of bleeding during muscle
biopsy procedure).

15. History of drug or alcohol abuse within the 12 months prior to the first dosing, or
evidence of such abuse as indicated by the laboratory assays conducted during
screening.

16. The Investigator should be guided by the following criteria during screening: a. Any
single laboratory parameter may not exceed 3 times the upper limit of normal (ULN). A
single parameter elevated up to and including 3 times the ULN should be re-checked
once more as soon as possible, and in all cases, at least prior to
enrollment/randomization, to rule out lab error. For abnormal liver function tests, in
the presence of elevated serum CK levels, ALT, or AST, up to 5 times the ULN are
acceptable if other liver tests are normal. b. If the total bilirubin concentration is
increased above 1.5 times the ULN, total bilirubin should be differentiated into the
direct and indirect reacting bilirubin. In any case, serum indirect bilirubin should
not exceed the value of 1.6 mg/dL (27 mol/L).

17. Use of drugs that are inhibitors of CYP3A4, 2B6, or 2C19 within 2 weeks prior to the
first dosing and during the study.

18. Use of drugs that are substrates of MATE1 or MATE2-K transporters within 2 weeks prior
to the first dosing and during the study.

19. Use of turmeric or products containing curcumin within 2 weeks prior to the first
dosing and during the study.

20. Use of aspirin or nonsteroidal anti-inflammatory agents within 3 days prior to the
baseline visit (due to the increased risk of bleeding during muscle biopsy procedure).

21. Any reason that, in the opinion of the Investigator, would prevent the subject from
participating in the study.

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

Eligibility last updated 10/13/22. Questions regarding updates should be directed to the study team contact.

• Patients must be 5 to 60 years of age at the time of enrollment
• Patients with newly diagnosed untreated histologically confirmed classic Hodgkin lymphoma (cHL) (nodular sclerosis, mixed cellularity, lymphocyte-rich, or lymphocyte-depleted, or not otherwise specified [NOS]) with stage I or II disease
• Patients must have bidimensionally measurable disease (at least one lesion with longest diameter >= 1.5 cm)
• Patients must have a whole body or limited whole body PET scan performed within 42 days prior to enrollment. PET-CT is strongly preferred. PET-MRI allowed if intravenous contrast enhanced CT is also obtained
• Pediatric patients (age 5-17 years) must have an upright posteroanterior (PA) chest X-ray (CXR) for assessment of bulky mediastinal disease. Adult patients must have either a CXR or CT chest
• Patients >= 18 years must have a performance status corresponding to Zubrod scores of 0, 1 or 2
• Patients =< 17 years of age must have a Lansky performance score of >= 50

• Pediatric patients (age 5-17 years): A serum creatinine based on age/gender as follows (within 7 days prior to enrollment):

  • 2 to < 6 years (age): 0.8 mg/dL (male), 0.8 mg/dL (female)
  • 6 to < 10 years (age): 1 mg/dL (male), 1 mg/dL (female)
  • 10 to < 13 years (age): 1.2 mg/dL (male), 1.2 mg/dL (female)
  • 13 to < 16 years (age): 1.5 mg/dL (male), 1.4 mg/dL (female)
  • >= 16 years (age): 1.7 mg/dL (male), 1.4 mg/dL (female) OR a 24 hour urine creatinine clearance >= 50 mL/min/1.73 m^2 (within 7 days prior to enrollment) OR a glomerular filtration rate (GFR) >= 50 mL/min/1.73 m^2 (within 7 days prior to enrollment). GFR must be performed using direct measurement with a nuclear blood sampling method OR direct small molecule clearance method (iothalamate or other molecule per institutional standard)
  • Note: Estimated GFR (eGFR) from serum or plasma creatinine, cystatin C or other estimates are not acceptable for determining eligibility
• For adult patients (age 18 years or older) (within 7 days prior to enrollment): Creatinine clearance >= 30 mL/min, as estimated by the Cockcroft and Gault formula or a 24-hour urine collection. The creatinine value used in the calculation must have been obtained within 28 days prior to registration. Estimated creatinine clearance is based on actual body weight

• Total bilirubin =< 2 x upper limit of normal (ULN) (within 7 days prior to enrollment)

  • Unless due to Gilbert's disease, lymphomatous involvement of liver or vanishing bile duct syndrome

• Aspartate aminotransferase (AST) =< 3 x ULN (within 7 days prior to enrollment)

  • Unless due to Gilbert's disease, lymphomatous involvement of liver or vanishing bile duct syndrome

• Alanine aminotransferase (ALT) =< 3 x ULN (within 7 days prior to enrollment)

  • Unless due to Gilbert's disease, lymphomatous involvement of liver or vanishing bile duct syndrome
• Shortening fraction of >= 27% by echocardiogram (ECHO), multigated acquisition scan (MUGA), or functional cardiac imaging scan (within 7 days prior to enrollment) or ejection fraction of >= 50% by radionuclide angiogram, ECHO, MUGA, or cardiac imaging scan (within 7 days prior to enrollment)
• Diffusion capacity of the lung for carbon monoxide (DLCO) >= 50% of predicted value as corrected for hemoglobin by pulmonary function test (PFT) (within 7 days prior to enrollment). If unable to obtain PFTs, the criterion is: a pulse oximetry reading of > 92% on room air
• Known human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
• For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated. Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load

• Patients with nodular lymphocyte predominant Hodgkin lymphoma
• Patients with a history of active interstitial pneumonitis or interstitial lung disease
• Patients with a diagnosis of inherited or acquired immunodeficiency that is poorly controlled or requiring active medications, such as primary immunodeficiency syndromes or organ transplant recipients
• Patients with any known uncontrolled intercurrent illness that would jeopardize the patient's safety such as infection, autoimmune conditions, cardiac arrhythmias, angina pectoris, and gastrointestinal disorders affecting swallowing and/or absorption of pills

• Patients with a condition requiring systemic treatment with either corticosteroids (defined as equivalent to > 10 mg daily prednisone for patients >= 18 years or > 0.5 mg/kg [up to 10 mg/day] for patients < 18 years) or other immunosuppressive medications within 14 days prior to enrollment

  • Note: Replacement therapy such as thyroxine, insulin, or physiologic corticosteroid for adrenal or pituitary insufficiency is not considered a form of systemic treatment. Inhaled or topical steroids, and adrenal replacement doses (=< 10 mg daily for patients >= 18 years or =< 0.5 mg/kg [up to 10 mg/day] prednisone equivalents) are permitted in the absence of active autoimmune disease
  • Note: Steroid use for the control of Hodgkin lymphoma symptoms is allowable, but must be discontinued by cycle 1, day 1
• Patients with peripheral neuropathy > grade 1 at the time of enrollment or patients with known Charcot-Marie-Tooth syndrome
• Patients with a prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen
• Administration of prior chemotherapy, radiation, or antibody-based treatment for cHL
• Prior solid organ transplant
• Prior allogeneic stem cell transplantation
• Live vaccine within 30 days prior to planned day 1 of protocol therapy (e.g., measles, mumps, rubella, varicella, yellow fever, rabies, bacillus calmette guerin [BCG], oral polio vaccine, and oral typhoid). Administration of messenger ribonucleic acid (mRNA) vaccines are permitted
• Female patients who are pregnant since fetal toxicities and teratogenic effects have been noted for several of the study drugs. A pregnancy test within 28 days prior to enrollment is required for female patients of childbearing potential
• Lactating females who plan to breastfeed their infants starting with the first dose of study therapy and for at least 6 months after the last treatment

• Sexually active patients of reproductive potential who have not agreed to use a highly effective contraceptive method (failure rate of < 1% per year when used consistently and correctly) for the duration of their study drug therapy. Following therapy, patients will be advised to use contraception as per institutional practice or as listed below for investigational agents, whichever is longer

  • Men and women of childbearing potential must continue contraception for a period of 6 months after last dose of brentuximab vedotin
  • Women of child-bearing potential (WOCBP) must continue contraception for a period of at least 5 months after the last dose of nivolumab
• All patients and/or their parents or legal guardians must sign a written informed consent
• All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met

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

Eligibility last updated 8/1/23. Questions regarding updates should be directed to the study team contact.

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

Eligibility last updated 12/9/22. Questions regarding updates should be directed to the study team contact.

• Fifteen obese (BMI 30-50 kg/m2) older (65-85 years) adults.
• 15 normal weight (BMI 18.5-28 kg/m^2) older adults.
• 15 obese young adults (18-35 years).
• 15 normal weight young adults will be recruited.
• Participants will be weight-stable (≥ 3 months).
• Sedentary men and women.

• Participation in ≥ 30 minutes of structured physical activity ≥ 2 days per week.
• Smoking/tobacco use.
• Alcohol/substance abuse.
• Pregnancy and breastfeeding.
• Anemia.
• Abnormal renal function.
• Blood clotting disorders.
• Coronary artery disease.
• Uncontrolled thyroid disease.
• Liver disease.
• Use of medications known to influence the main outcomes of the study.
• Orthopedic problems that may be aggravated by exercise.
• Chronic disease at the discretion of the investigators.

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

Eligibility last updated 8/16/23. Questions regarding updates should be directed to the study team contact.

• Subjects will be recruited 1 year from their most recent live birth.
• 30 with Gestational Diabetes Mellitus (GDM) in the preceding pregnancy.
• 30 with no history of GDM.

• Individuals < 20 or > 40 years at the preceding pregnancy.
• Active systemic illness.
• Preceding multiple gestation pregnancy.
• Taking medication that affects glucose metabolism.
• Upper GI surgery that alters gastric emptying.
• Current BM I< 25kg/m^2.
• For the GDM group, those with GDM in any pregnancy prior to the most recent pregnancy will be excluded (to reduce within group heterogeneity).
• Currently pregnant or breastfeeding. At a screening visit, subjects will provide consent and undergo a history and physical. They will have an EKG, blood draw for complete blood count, fasting glucose, HbA1c and chemistry group, and a pregnancy test. Subjects will be excluded if HbA1c is > 5.6% or fasting glucose is > 100mg/dL. Body composition will be measured using dual-energy X-ray absorptiometry (iDXA scanner; GE Wauwatosa, WI).

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

Eligibility last updated 4/18/23. Questions regarding updates should be directed to the study team contact.

• Patients will be recruited if they already have MRI scans, DXA scans for bone mineral density, and radiographs of the lumbar spine within the last year.
• Three patient groups will be recruited; the first group includes twenty healthy patients with no history of spine disorders or low back pain. The second group includes twenty patients with symptomatic DD, according to the Pfirrmann grading system. The third group includes scoliotic patients (with deformity ≥ 15°).

• Individuals with prior spine, knee, or hip surgery within the last year will be excluded. Patients without imaging data will be excluded. Patients who are not able to perform the physical activities will be excluded. BMI ≥ 35.

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

Eligibility last updated 9/11/23. Questions regarding updates should be directed to the study team contact.