• Age 18+.
• Able to give informed consent.
• Newly diagnosed metastatic renal cell carcinoma.
• Eligible for immunotherapy.

• Unable of unwilling to provide informed consent.
• Previous systemic therapy.

Eligibility last updated 8/11/21. Questions regarding updates should be directed to the study team contact.

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

Eligibility last updated 9/19/22. Questions regarding updates should be directed to the study team contact.

• Patient must have the ability to understand and the willingness to sign a written informed consent document.
• Patients with impaired decision-making capacity (IDMC) who have a legally authorized representative (LAR) or caregiver and/or family member available will also be considered eligible.
• Patient must have a diagnosis of high grade upper tract urothelial carcinoma proven by biopsy within 60 days prior to registration with one of the following:
  • Upper urinary tract mass on cross-sectional imaging; or
  • Tumor directly visualized during upper urinary tract endoscopy before referral to medical oncology;
    • NOTE: Biopsy is standard of care (SOC) and required for enrollment to study. This is vital for best practice.
  • Leukocytes ≥ 3,000/mcL (obtained ≤ 14 days prior to registration);
  • Platelets ≥ 100,000/mcL (obtained ≤ 14 days prior to registration);
  • Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) (or ≤ 2.5 x ULN for patients with Gilbert's disease) (obtained ≤ 14 days prior to registration);
  • Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) ≤ 2.5 x institutional ULN (obtained ≤ 14 days prior to registration);
  • Hemoglobin (Hgb) ≥ 9 g/dL (obtained ≤ 14 days prior to registration);
    • NOTE: Packed red blood transfusion is allowed to achieve this parameter as per treating investigator.
  • Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial;
    • NOTE: These patients must be stable on their anti-retroviral regimen with evidence of at least two undetectable viral loads within the past 6 months on the same regimen; the most recent undetectable viral load must be within the past 12 weeks. They must have a CD4 count of greater than 250 cells/mcL over the past 6 months on this same anti-retroviral regimen and must not have had a CD4 count < 200 cells/mcL over the past 2 years, unless it was deemed related to the cancer and/or chemotherapy induced bone marrow suppression. They must not be currently receiving prophylactic therapy for an opportunistic infection and must not have had an opportunistic infection within the past 6 months.
    • NOTE: For patients who have received chemotherapy in the past 6 months, a CD4 count < 250 cells/mcL during chemotherapy is permitted as long as viral loads were undetectable during this same chemotherapy. They must have an undetectable viral load and a CD4 count ≥ 250 cells/mcL within 7 days of registration.
• For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.
  • NOTE: Testing for HIV, hepatitis B or hepatitis C is not required unless clinically indicated.
• Patients with a history of hepatitis C virus (HCV) infection must have been treated and have undetectable viral load. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load.
• Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better.
• Patient must have a body weight of > 30 kg.
• Patient must have a life expectancy of ≥ 12 weeks.
• Patient must have a creatinine clearance > 15 ml/min as by Crockroft-Gault or 24-hour creatinine clearance within 28 days prior to registration.
  • NOTE: Patients will be assigned to cisplatin-ineligible and cisplatin-eligible cohorts based on their creatinine clearance, Eastern Cooperative Oncology Group (ECOG) performance status, and grade (if any) of peripheral neuropathy and hearing loss in keeping with SOC cisplatin contraindications.
• Patients that are cisplatin-eligible will be randomized to either Arm A or Arm B.
• Patients that meet the following criteria will be assigned to the cisplatin-ineligible Arm C:
  • Creatinine clearance of > 15 ml/min and ≤ 50 ml/min;
  • Patient must have an absolute neutrophil count (ANC) ≥ 1,000/mcL obtained ≤ 14 days prior to registration;
  • Patient must have ECOG performance status 0-2.
• Patients that meet the following criteria will be randomized to cisplatin-eligible Arm A or Arm B:
  • Patient must have an absolute neutrophil count (ANC) ≥ 1,500/mcL obtained ≤ 14 days prior to randomization;
  • Patient must have ECOG performance status 0-1;
  • Patient must have left ventricular ejection fraction (LVEF) ≥ 50% by (either multigated acquisition scan [MUGA] or 2-D echocardiogram) obtained within 28 days prior to randomization;
  • Patient must not have peripheral neuropathy ≥ grade 2 or hearing loss ≥ grade 3.

• Patients must not have any component of small cell carcinoma. Other variant histologic types are permitted provided the predominant (≥ 50%) subtype is urothelial carcinoma.
• Patients must not be pregnant or breast-feeding due to the potential harm to an unborn fetus and possible risk for adverse events in nursing infants with the treatment regimens being used. All patients of childbearing potential must have a blood test or urine study within 14 days prior to registration to rule out pregnancy. A patient of childbearing potential is defined as any patient, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria:
  • Has achieved menarche at some point;
  • Has not undergone a hysterectomy or bilateral oophorectomy; or
  • Has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months);
  • Patients of childbearing potential and sexually active patients must not expect to conceive or father children by using accepted and effective method(s) of contraception or by abstaining from sexual intercourse from the time of registration, while on study treatment and for at least 6 months after the last dose of protocol treatment.
• Patient must have no evidence of metastatic disease or clinically enlarged lymph nodes (≥ 1.0 cm short axis) on imaging required within 28 days prior to registration (solitary slightly enlarged lymph node with negative biopsy is allowed).
  • NOTE: Patients with elevated alkaline phosphatase, calcium or suspicious bone pain/tenderness should also undergo baseline bone scans to evaluate for bone metastasis.
• Patient must not have another active (or within 2 years) second malignancy other than resected non-melanoma skin cancers, resected in situ breast, cervical or other in situ carcinoma, and either clinically insignificant per the investigator (e.g., ≤ Gleason 3+4) on surveillance or previously treated prostate cancer with no rising prostate specific antigen (PSA) and no plan to treat.
  • NOTE: Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.
• Patients in whom concomitant or prior bladder/urethra predominant (≥ 50%) urothelial carcinoma have been surgically resected and demonstrated to be only non-invasive cancer (< cT1N0) are eligible regardless of time elapsed.
• Patient must not have any uncontrolled illness including, but not limited to, ongoing or active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and tuberculosis [TB] testing in line with local practice), symptomatic congestive heart failure (CHF), myocardial infarction (MI) in last 3 months, or unstable angina pectoris, significant uncontrolled cardiac arrhythmia, liver cirrhosis, interstitial lung disease, or psychiatric illness/social situations that would limit compliance with study requirements.
• Patient must not have received prior radiation therapy to ≥ 25% of the bone marrow for other diseases.
• Patient must not have received prior systemic anthracycline therapy.
  • NOTE: Patients who have received prior intravesical chemotherapy at any time for non-muscle invasive urothelial carcinoma of the bladder are eligible.
• Patient must not have an active autoimmune disease requiring immunosuppressive therapy within 2 years prior to registration or a history of inflammatory bowel disease (inflammatory bowel disease [IBD], colitis, or Crohn's disease), systemic lupus erythematosus, Sarcoidosis syndrome, Wegener syndrome or immune-related pneumonitis or interstitial lung disease.
• Patients with well-controlled hyper/hypothyroidism, celiac controlled by diet alone, diverticulosis, diabetes mellitus type I, vitiligo, alopecia, psoriasis, eczema, lichen planus, or similar skin/mucosa condition.
• Patient must not be on or have used immunosuppressive medication within 14 days prior to the first dose of MEDI4736 (MEDI4736 (durvalumab). The following are exceptions to this criterion:
  • Intranasal, inhaled, intra-auricular, topical steroids, or local steroid injections (e.g., intra-articular injection;
  • Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent at the time of enrollment;
  • Steroids as premedications for hypersensitivity reactions (e.g., computed tomography [CT] scan premedication);
  • Patient must not have a concomitant primary urothelial carcinoma of the bladder and/or urethra;
  • NOTE: Patients in whom concomitant or prior bladder/urethra predominant (≥ 50%) urothelial carcinoma have been surgically resected and demonstrated to be only non-invasive cancer (< cT1N0) are eligible regardless of time elapsed.
• Patient must not have prior history of muscle-invasive urothelial carcinoma with or without systemic chemotherapy (T2-4a and/or N1) within 2 years prior to registration.
  • NOTE: Patients who have no evidence of disease (NED) for more than 2 years from the latest therapy (surgery, radiation, chemotherapy, or clinical trial).
• Patient must not have received live attenuated vaccine within 30 days prior to the first dose of MEDI4736 (durvalumab), while on protocol treatment and within 30 days after the last dose of MEDI4736 (durvalumab).
• Patient must not have had a major surgical procedure (as defined by the Investigator) within 28 days prior to registration.
• Patient must not have a history of allogenic organ transplantation.

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

Eligibility last updated 3/22/23. Questions regarding updates should be directed to the study team contact.

• ≥ 21 years old.
• Diagnosis of Type 2 diabetes.
• Use of ≥ study drug (GLP-1RA, SGLT2i, DPP-4i, SU).

• Insulin use.
• Cognitive impairment.
• Terminal or advanced illness.
• Non-English speaking.
• Residency in a long-term care setting.

• Adult 18 years and older.
• English speaking.
• Able to provide consent.
• Has a qualifying indication for cardiac rehabilitation (e.g., Acute coronary syndrome, myocardial infarction, percutaneous coronary intervention, coronary artery bypass grafting, and stable angina, heart valve disease) and able to participate in cardiac rehabilitation.
• Olmsted County MN residents. 

• Individuals < 18 years of age.
• Unwilling to provide consent.
• Unable to participate in cardiac rehab.

Eligibility last updated 8/13/21. Questions regarding updates should be directed to the study team contact.

Inclusion Criteria:

• Patient with pathologically confirmed HCC not amenable to curative resection, transplantation or ablative therapies.
• Have radiographically measurable disease by RECIST.
• Eligible for atezolizumab/bevacizumab front line therapy.
• Male or female with age greater than 18 years, with the capacity and willingness to provide written informed consent.

• Pregnant and/or breast-feeding patients. A negative pregnancy test within 48 hours of the PET scan.
• Patients with higher than the weight/size limitations of PET/CT scanner.

• Participants eligible for this study will be patients on the NOHARM trial registry (e.g., patients that were automatically assigned to receive the NOHARM intervention as part of their surgical care) and/or their charts and members of their care teams, including nurses, doctors, physical therapists, nurse practitioners and physician assistants, and medical assistants.  

• Individuals not on the NOHARM trial registry.

Eligibility last updated 8/13/21. Questions regarding updates should be directed to the study team contact.

Inclusion Criteria

1. First allogeneic HSCT, in ≤ CR2, and MRD negative prior to transplant (including
matched sibling, MUD with at least 6 of 8 HLA markers, or haploidentical with at least
5 of 10 HLA markers) as:

- Adjuvant therapy for AML (Group 1) at 90 days (±10 days) post-HSCT defined as
patients with CRMRD; or

- Treatment for refractory/relapsed AML (first relapse post-HSCT) when disease
occurs after transplant (Group 2) defined as

- First relapse (MRD+ or frank relapse) post-HSCT

- Patients in Arm 1B (SOC) who experience first relapse (MRD+ or frank
relapse) post HSCT

- Safety Lead-in defined as patients who fit all the criteria for Group 2 only

2. Are ≥18 years of age

3. Karnofsky/Lansky score of ≥60

4. Life expectancy ≥12 weeks

5. Adequate blood, liver, and renal function

- Blood: Hemoglobin ≥7.0 g/dL (can be transfused)

- Liver: Bilirubin ≤2X upper limit of normal; aspartate aminotransferase ≤3X upper
limit of normal

- Renal: Serum creatinine ≤2X upper limit of normal or measured or calculated
creatinine clearance ≥45mL/min

7. Patients are allowed to be on experimental conditioning regimens prior to transplant if
no planned maintenance therapy post-transplant.

8. In Group 2, patients may receive bridging therapy at the investigators' discretion in
situations where MT-401 is not ready for administration or the treating physician believes
the patient would benefit

Exclusion Criteria

1. Clinically significant or severely symptomatic intercurrent infection

2. Pregnant or lactating

3. For Group 1, anti-neoplastic therapy after HSCT and prior to or during dosing of
MT-401

4. For Group 2, concomitant anti-neoplastic therapy during or after dosing of MT-401

5. Evidence of acute or chronic GVHD ≥Grade 2 (exception: acute or chronic Grade 2 GVHD
of skin allowed if stable) within one week prior to receiving MT-401

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

Eligibility last updated 12/27/22. Questions regarding updates should be directed to the study team contact.

• Specimens (dried blood spots, whole blood, or retrospectively available cultured cells) from Barth subjects and controls identified by the Barth Syndrome Foundation and/or clinical testing at the Mayo Clinic Biochemical Genetics Laboratory.
• Residual specimens from the Mayo Clinic Biochemical Genetics Laboratory:
  • Up to 1,000 control subjects from pediatric and adult populations through age 99 on date of relevant specimen collection.
• Data collected as part of the Barth Syndrome Foundation Registry and Biorepository and/or clinical testing at the Mayo Clinic Biochemical Genetics Laboratory.

• None.

Eligibility last updated 8/13/21. Questions regarding updates should be directed to the study team contact.

• Men or women.
• 22 to 80 years old.
• Unruptured cerebral aneurysm scheduled for flow diverter treatment at St. Marys Hospital.
• Patients who may require pre-treatment with Lorazepam/Ativan prior to MRI scanning provided they have an adult accompanying and driving for them after the scan is completed.

• Any prior stent or coil treatments.
• IVC filter removal in last twelve months.
• Unable to have MRI imaging exams due to coil, filter, stent or wire or an implanted device such as IVC filter, pacemaker, nerve stimulator, medication pump or other on body injector delivery system/sensor or tattoo ink that if it contained metal could heat up and/or or generate image artifact.  
• Not able to return for follow-up MRI imaging and blood collection in three to twelve months post flow diversion (FD) treatment.
• Pregnant or breast-feeding females.
• Cancer diagnosis and having had (last twelve months) or currently undergoing radiation and/or chemotherapy treatments.
• Persons lacking capacity.
• Prisoner.

Eligibility last updated 8/30/21. Questions regarding updates should be directed to the study team contact.

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

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

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

Eligibility last updated 12/13/22. Questions regarding updates should be directed to the study team contact.

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

Eligibility last updated 9/20/22. Questions regarding updates should be directed to the study team contact.

• Age 50 years or older.
• English speaking.
• Admitted to the intensive care unit (medical or surgical).
• Expected mechanical ventilator support for ≥ 48 hours.
• Consentable through a legally authorized representative.
• Have access to a telephone (after discharge).

• History of dementing illnesses and other neurodegenerative diseases such as Alzheimer’s disease or vascular dementia.
• Psychiatric illness which is not well controlled.
• Alcohol withdrawal symptoms/concern for withdrawal.
• Suspected or confirmed drug intoxication/overdose.
• Traumatic brain injury, ischemic or hemorrhagic cerebrovascular accident, or undergoing neurosurgery.
• Uncorrected hearing or vision impairment including legal blindness.
• Incarcerated at the time of study enrollment.
• Enrolled in another clinical trial which does not permit co-enrollment.
• Any medical condition precluding safe use of headphones such as:  skin breakdown, burns, facial or skull fractures.
• COVID-19 positive test.

• Women and men between 18 and 85 years of age.
• Chest radiograph or computed tomography (CT) of the thorax within the last 1 year not demonstrating any abnormality considered to be significantly contributing to the refractory chronic cough in the opinion of the Principal Investigator.
• Have a diagnosis of refractory chronic cough or unexplained cough for at least one year.
• Have a score of ≥ 40mm on the Cough Severity VAS at Screening.
• Women of child-bearing potential (defined in supplemental section 1, page 64) must agree to use 2 forms of acceptable birth control and make no donation of eggs from Screening through the end of the 8-week study period. Acceptable birth control methods include established use of oral, injected, or implanted hormonal methods of contraception; intrauterine device (IUD) or intrauterine system (IUS); tubal ligation; or male sterilization. Double-barrier method (diaphragm for female subject and condom for male partner with spermicidal) satisfies the requirement for 2 forms of acceptable birth control. When concordant with the preferred lifestyle of the subject, true and complete abstinence (not periodic abstinence) is acceptable.
• Male subjects and their partners of child-bearing potential must use 2 methods of acceptable birth control, 1 of which must be a barrier method, and make no donation of sperm from Screening until 3 months after the last dose of study drug at the end of 8 weeks.
• Have provided written informed consent.
• Are willing and able to comply with all aspects of the protocol.

• Current smoker (cigarettes, e-cigarettes or marijuana) or former smokers who have smoked within the past 12 months.
• Former smokers with > 20 pack-year history of smoking.
• Ongoing treatment with an ACE-inhibitor that is considered as the potential cause of a subject’s cough or requiring treatment with an ACE-inhibitor during the study or within 12 weeks prior to the Screening/Baseline Visit (Day -14 to Day 0).
• FEV1/FVC < 60%.
• History of upper or lower respiratory tract infection or recent significant change in pulmonary status within 4 weeks of the Screening/Baseline Visit (Day -14 to Day 0).
• History of opioid use specifically prescribed for chronic cough within 2 weeks of the Screening/Baseline Visit (Day -14 to Day 0). Use of opioids for other indications (for example, to treat pain) is permitted.
• History of baclofen use specifically prescribed for chronic cough within 2 weeks of the Screening/Baseline Visit (Day -14 to Day 0). Use of baclofen for other indications (for example, to treat spasticity) is permitted.
• Diagnosis of COPD, bronchiectasis, interstitial lung disease or cystic fibrosis.
• Presence of an untreated or undertreated cause for the patient’s chronic cough (as determined by the treating/referring physician per ACCP guidelines). e.g. uncontrolled asthma, GERD or post-nasal drainage that could potentially explain the patient’s chronic cough.
• Requiring concomitant therapy with prohibited medications (see under ‘prohibited concomitant therapy’ on page 28).
• Treatment with any pharmaceutical or biological investigational therapy (excluding coronavirus disease of 2019 (COVID) vaccination and COVID related monoclonal antibody therapy).
• Participation in another clinical trial that does not allow co-enrollment within 4 weeks prior to the Screening/Baseline Visit (Day -14 to Day 0).
• Total bilirubin, alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 3 x the upper limit of normal (ULN) during screening.
• Serum creatinine < 30 mL/min, hemodialysis or peritoneal dialysis.
• Advanced liver disease as defined by the presence of cirrhosis and/or signs of portal hypertension.
• History of previous hypersensitivity or intolerance to Duloxetine & Amitriptyline (patients who have previously been on either amitriptyline or duloxetine for chronic cough or other reasons and have tolerated the medication will be offered participation regardless of previous response to therapy).
• Currently pregnant or breastfeeding female subject.
• Presence of any medical condition or disability that the investigators believe could interfere with the assessment of safety or efficacy in this trial or compromise the safety of the subject.
• Planned or anticipated major surgical procedure or other activity that would interfere with the subject’s ability to comply with protocol-mandated assessments (e.g., extended travel) during the subject’s participation in the study.
• Currently taking either another SSRI, SNRI or MAO inhibitor which the patient cannot safely discontinue at least 2 weeks prior to the screening period.

Eligibility last updated 4/15/22. Questions regarding updates should be directed to the study team contact.

Eligibility last updated  2/21/23. Questions regarding updates should be directed to the study team contact.

• Eligible particiants between the ages of 18 and 90.
• Either a family or personal history of cancer and/or a family or personal history of genetic variants in cancer predisposition genes.
• Participants may also be those who have tested negatively for genetic variants in cancer predisposition genes.

• This project does not involve prisoners or children.

Eligibility last updated 8/16.21. Questions regarding updates should be directed to the study team contact.

•  Documented diagnosis of PH1, per physician’s determination.
• Written patient consent (per local regulations or ethics committee requirements) obtained prior to enrollment. If the patient is under the age of legal consent, written consent must be obtained from their legal guardian, and the patient should provide assent per local and national requirements. Should they become adults during their participation in the study, they will review and sign the adult consent, as applicable. Consent may be obtained from a legal representative if required and permitted by country-specific regulations or requirements.

• Currently enrolled in a clinical trial for any investigational agent.

• Female age 18 or older at the time of signing informed consent.
• Ultrasound confirmation of singleton pregnancy.
• GA ≥ 9 weeks at the time of first sample collection.
• Willing and able to provide written informed consent.
• Willing and able to comply with study procedures, including blood sample and neonatal buccal swab.
• Cohort 1: Ultrasound confirmation of VT Pregnancies:
  • Ultrasound confirmation of VT;
  • Spontaneous fetal demise of one twin or empty sac.
• Cohort 2: High Risk for VT Pregnancies:
  • Panorama yielding “high risk for twin/VT/triploidy” result;
  • Ultrasound confirmation of single gestation;
  • No evidence of triploidy.

• Known monozygotic twin pregnancy.
• Multiple gestation.
• VT pregnancy resulting from iatrogenic fetal demise.
• GA < 9 weeks.
• Evidence of triploidy other than Panorama test results.
• Any confounding complication or condition that, in the opinion of the investigators, precludes participation in the study; this may include a cancer diagnosis, organ transplant, pregnancy utilizing an egg donor, or other findings that may interfere with interpretation of Panorama results.

Eligibility last updated 10/19/21. Questions regarding updates should be directed to the study team contact.

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

Eligibility last updated 9/21/22. Questions regarding updates should be directed to the study team contact.

Prescreening Criteria:

• Diagnosed with NASH on prior liver biopsy.
• Type 2 diabetes with high waist circumference or obesity or hepatic steatosis on ultrasound.
• At least 3 of the components of metabolic syndrome.

• Male or female, aged ≥ 18 years at the time of signing informed consent.
• Upon central biopsy reading process: diagnosis of NASH according to the Steatosis-Activity-Fibrosis (SAF):
  • Steatosis score ≥ 1;
  • Activity score: A3 or A4;
  • Fibrosis score: F2 or F3.
• No qualitative change in dose for the drugs listed below:
  • Antidiabetic treatment if glucagon-like peptide-1 receptor agonists (GLP1 receptor agonists) or sodium-glucose co-transporter-2 inhibitors (SGLT2 inhibitors): for at least 3 months;
  • Vitamin E (if at a dose ≥ 400 IU/day): for at least 6 months;
  • Statins: for at least 3 months;
  • No qualitative change in dose for all other chronically administered drugs for at least 3 months prior to Screening.
• Weight stable for 6 months prior to Screening and between the qualifying liver biopsy and Baseline (no more than 5% change for both periods).
• Negative serum pregnancy test at study Screening for females of childbearing potential confirmed by central laboratory. Females of childbearing potential must practice a consistent and proper use of highly effective method of contraception throughout the study and for 1 month after treatment discontinuation.

Liver-related:

• Documented causes of chronic liver disease other than NASH.
• Histologically documented liver cirrhosis (fibrosis stage F4).
• History or current diagnosis of hepatocellular carcinoma (HCC).
• History of or planned liver transplant.
• Positive human immunodeficiency virus (HIV) serology.
• ALT or AST > 5 × ULN.
• AST< 0.6 ULN if the liver biopsy has to be performed in the scope of the study.
• Abnormal synthetic liver function as defined by Screening central laboratory evaluation.
• Haemoglobin < 110 g/L (11 g/dL) for females and < 120 g/L (12 g/dL) for males.
• Patient currently receiving any approved treatment for NASH or obesity.
• Current or recent history (< 5 years) of significant alcohol consumption.
• Treatment with drugs that may cause non-alcoholic fatty liver disease (NAFLD) administered for at least 2 weeks within 12 months prior to qualifying liver biopsy.

Glycaemia related:

• HbA1c >9% at Screening.
• Diabetes mellitus other than type 2.
• Current treatment with insulin.Treatment with PPAR-gamma agonists (thiazolidinediones [TZDs]) 12 months before screening or historical biopsy.

Obesity related:

• Bariatric surgery: Restrictive procedures are allowed, if performed > 6 months prior to the qualifying liver biopsy; malabsorptive procedures and procedures combining both restrictive and malabsorptive methods are not allowed within 5 years of the qualifying liver biopsy.

Cardiovascular related:

• History of heart failure with reduced left ventricular ejection fraction (LVEF).
• Atrial fibrillation requiring anticoagulation
• Unstable heart failure.
• Uncontrolled hypertension at Screening (values > 160/100 mm Hg).

General safety:

• Women currently breastfeeding.
• Previous exposure to lanifibranor.
• Participation in any clinical trial investigational medicinal product/device within 3 months from Screening or 5 half-lives from Screening, whichever is longer.
• Concomitant treatment with PPAR-alpha agonists (fibrates).

Eligibility last updated 5/22/23.  Questions regarding updates should be directed to the study team contact.

• Adult patient, aged 18 or older.
• English-speaking.
• Patients who have reported evidence of hiccups in the past five years.
• Patients who upon contact describe having had hiccups.

• Individuals < 18 years of age.
• Have not experienced hiccups in the past five years.

Eligibility last updated 8/16/21. Questions regarding updates should be directed to the study team contact.

• Previously participated in a prior study and expressed willingness to be recontacted or who respond to intramural and extramural adverts.
• We propose three groups: 10 individuals who have NFG/NGT, 10 individuals with prediabetes (IGT) and 10 individuals with type 2 diabetes (T2DM).

• Medications that can affect glucose metabolism (to be determined by PI) or in the case of participants with T2DM taking pioglitazone.
• For female subjects: positive pregnancy test.
• Any active systemic illness.
• Upper gastrointestinal surgery.

Eligibility last updated 8/20/21. Questions regarding updates should be directed to the study team contact.

Eligibility last updated 2/22/23 to match clinicaltrials.gov. Questions regarding updates should be directed to the study team contact.

• Men who are currently receiving androgen deprivation therapy (ADT) for the treatment of prostate cancer. ADT is defined by a history of orchiectomy, or ongoing usage of gonadotropin-releasing hormone agonists or antagonists.
• Men receiving next generation androgen axis inhibitor therapies including abiraterone, enzalutamide, apalutamide, and darolutamide are eligible.
• Patients must be on a stable dose of all hormone-directed therapies for at least 28 days prior to registration and must not be planning to discontinue this therapy for at least 42 days following registration.
• Patients receiving radiation therapy during the study period are eligible.
• Eligible patient must have bothersome hot flashes for ≥ 14 days prior to registration, defined by an occurrence of ≥ 28 times per week and of sufficient severity to cause the patient to seek therapeutic intervention.
• Life expectancy of greater than 6 months.
• Eastern Cooperative Oncology Group (ECOG) performance status
  •0, 1, or 2.
• In order to complete the mandatory patient-completed measures, participants must be able to speak and/or read English.

• No current use or future planned use of any of the following agents during the study period: drugs that are not Food and Drug Administration (FDA) approved for use in humans, androgens, estrogens, progesterone analogs, gabapentin, selective serotonin reuptake inhibitor (SSRI)/serotonin and norepinephrine reuptake inhibitor (SNRI) anti-depressants, cholinergic agonists, cholinesterase inhibitors, or complementary/alternative medicine taken for the purpose of managing hot flashes. Prior use of these agents is permitted as long as they are discontinued before registration.
• No current or prior use of oxybutynin.
• Patients with a history of any of the following contraindications to oxybutynin are not eligible:
  • gastroparesis or gastrointestinal obstructive disorders;
  • significant gastric reflux symptoms not controlled by medication; ulcerative colitis;
  • narrow-angle glaucoma;
  • urinary retention requiring indwelling or intermittent self-catheterization within the prior 6 months;
  • hypersensitivity to oxybutynin or any other components of the product; current uncontrolled hyperthyroidism;
  • uncontrolled coronary artery disease or a history of myocardial infarction within the prior 12 months;
  • New York Heart Association (NYHA) class II-IV congestive heart failure;
  • symptomatic cardiac arrhythmias;
  • current uncontrolled hypertension;
  • myasthenia gravis; or
  • dementia.

Eligibility last updated 11/22/21. Questions regarding updates should be directed to the study team contact.

• Diagnosis of functional nasal obstruction or aesthetic nasal concern requiring nasal surgery with costal cartilage harvest.
• Male or female with age ≥ 18 years.
• Willing and able to understand and provide written informed consent.

• Age < 18 years of age.
• Known pregnancy.
• Women who are currently nursing a child.
• History of coagulopathy; such as hemophilia or Von Willebrand disease, or any congenital or acquired bleeding disorder.
• Use of anticoagulation medication during the study; i.e. aspirin, Coumadin, Plavix, or medications similar in class to these medications will exclude the patient from participation.
• Inability to provide informed consent (patients under guardianship).
• Known hypersensitivity to local anesthetics
• History of cardiac disease; such as current impaired cardiovascular function, past history of myocardial infarction, congenital heart disease, current cardiac symptoms; i.e. angina, shortness of breath, or chest pain as determined by history or review of the medical record.
• History of complex pulmonary disease; such as uncontrolled asthma, COPD, or interstitial lung disease as determined by history or review of the medical record. 
• Impaired renal function as documented in the medical record in the last 3 months with a serum creatinine greater than 1.2 mg/dL or glomerular filtration rate < 60 mL/min/BSA as determined by history or review of the medical record.
• History of or current hepatic disease as documented by liver function test abnormality in the last 3 months as determined by history or review of the medical record. 

Eligibility last updated 8/16/21. Questions regarding updates should be directed to the study team contact.

Inclusion Criteria
•Participant:

• Age range 30- < 91 years with minimum life expectancy of at least 1 year.
• Willingness to return to study site for follow up at 1 month and 1 year.
• Fluent in English or Spanish.
• Willingness to have fingerstick blood sample collected to determine HbA1c level at entry and at 1 year. If determined to be diabetic at baseline, participant will be advised to seek medical care.

Inclusion Criteria
•Study Eye:

• Clinically recommended for DMEK, and able to schedule DMEK between 5 to 90 days after enrollment.
• Presence of a condition related to endothelial dysfunction which will be treated by DMEK.  Eligible indications for DMEK include:
  • Presence of Fuchs endothelial corneal dystrophy (FECD) meeting at least one of the following:
  • Phakic FECD with or without cataract;
  • Triple procedure including DMEK for FECD, cataract extraction and posterior chamber intraocular lens implantation (IOL) is allowed;
  • Pseudophakic FECD with posterior capsule supported, sulcus supported, or scleral-fixated posterior chamber IOL b. Pseudophakic corneal edema with posterior capsule supported, sulcus supported, or scleral-fixated posterior chamber IOL without FECD;
  • Failed Descemet stripping automated endothelial keratoplasty (DSAEK) or DMEK without exclusionary criteria, as described below.

• Pregnant or planning to become pregnant prior to the DMEK study surgery, based on verbal report.
• Lack cognitive capacity such that consent could not be provided.
• Presence of a condition that has a high probability for failure (e.g., failed penetrating keratoplasty, uncontrolled uveitis).
• Stromal vascularization that will impede assessment of recipient stroma clarity.
• Other primary endothelial dysfunction conditions including posterior polymorphous corneal dystrophy and congenital hereditary corneal dystrophy.
• Indication for surgery that is not suitable for DMEK (e.g, keratoconus, stromal dystrophies and scars).
• Aphakic corneal edema with or without FECD.
• Anterior chamber IOL in study eye prior to DMEK or planned placement of anterior chamber IOL during DMEK.
• Planned IOL exchange of an anterior chamber IOL with a posterior chamber IOL in study eye at time of study DMEK.
• Pre-operative central sub-epithelial or stromal scarring that could impact post-operative recipient stromal clarity assessment.
• Presence of anterior synechiae.
• Peripheral anterior synechiae in the angle greater than a total of three clock hours.
• Uncontrolled glaucoma with or without prior filtering surgery, tube shunt placement, or MIGS. Uncontrolled glaucoma is defined as intraocular pressure > 25mm Hg.
• Controlled glaucoma with prior tube shunt placement for glaucoma (controlled glaucoma with MIGS is allowed).
• Fellow eye visual acuity < 20/200 due to an ocular condition other than a cornea disease that would be a candidate for DMEK.
• IOP < 8 mmHg.
• Topical Rho kinase inhibitor, including Rhopressa, used within 1 month prior to study entry and anticipated during the course of the study.

Eligibility last updated 5/18/22. Questions regarding updates should be directed to the study team contact.

• Clinical diagnosis of diabetes based upon an elevated hemoglobin A1C.

• Diagnosis of Diabetic Nephropathy.
• Active or unresolved Diabetic Ketoacidosis (DKA).
• Steroid Induced Hyperglycemia.

Eligibility last updated 8/18/21. Questions regarding updates should be directed to the study team contact.