• Oropharynx or Oral Cavity Squamous Cell Carcinoma Patients: collected under the OPX Biomarker Protocol (IRB: 19-006036).
• Normal Controls:
  • Age ≥ 18 years;
  • Able to provide informed written consent documenting permission to give saliva sample for research testing;
  • Ability to complete questionnaire(s) by themselves or with assistance.

• Oropharynx or Oral Cavity Squamous Cell Carcinoma Patients: collected under the OPX Biomarker Protocol (IRB: 19-006036).
• Normal Controls:
  • Any personal history of head or neck cancer including head or neck skin cancer;
  • Other active malignancy ≤ 5 years prior to registration. 
  • EXCEPTIONS:  Non-melanotic skin cancer, non-metastatic prostate cancer. 
  • NOTE:  If there is a history of prior malignancy, they must not be receiving other specific treatment for their cancer.
  • Dry mouth (xerostomia) caused by any chronic (> 30 days) condition (known or unknown) or medication;
  • Recent (within 30 days) or active upper aerodigestive tract or anogenital infections.

• 100 subjects > 18 (200 eyes) with visual acuity at any level.

Exclusion Criteria:

• Patients with no ability to sign the consent forms with no LAR.
• Subjects with limited comprehension of English.

Eligibility last updated 10/18/21. 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.

Inclusion Criteria (Part A):

- Clinical or mutational diagnosis of TSC

- Failure to control seizures despite appropriate trial of 2 or more ASMs at therapeutic doses.

- Have at least 8 countable/witnessed primary seizures during the 4-week baseline period with at least 1 primary seizure occurring in at least 3 of the 4 weeks of baseline.

Inclusion Criteria (Part B):

-  Patients have experienced ≥ 35% reduction in primary seizure frequency during the Part A treatment period compared to the 4-week Baseline Period.

Exclusion Criteria (Part A):

- Previous exposure to GNX

- Pregnant or breastfeeding

- Concurrent use of strong inducers or inhibitors of cytochrome P450 (CYP)3A4/5/7. Any strong inhibitor or inducer of CYP3A4/5/7 must be discontinued at least 28 days before Visit 2, study drug initiation. This does not include approved ASMs.

- Patients who have been taking felbamate for less than 1 year prior to screening

- Patients who test positive for tetrahydrocannabinol (THC) or non-approved cannabidiol (CBD) via plasma drug screen

- Chronic use of oral steroid medications, ketoconazole (except for topical formulations), St. John's Wort, or other IPs is not permitted

- Have an active CNS infection, demyelinating disease, degenerative neurological disease, or CNS disease deemed progressive. This includes tumor growth which in the
opinion of the investigator could affect primary seizure control

- Patients with significant renal insufficiency, estimated glomerular filtration rate (eGFR) < 30 mL/min (calculated using the Cockcroft-Gault formula or Pediatric GFR
calculator or Bedside Schwartz), will be excluded from study entry or will be discontinued if the criterion is met post baseline

- Have been exposed to any other investigational drug within 30 days or fewer than 5 half lives (whichever is shorter) prior to the screening visit

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

Eligibility last updated 12/28/23. Questions regarding updates should be directed to the study team contact.

• Either a community leader with insights and opinions about complex care among Spanish speaking populations or a patient, family member, caregiver with recent experience of complex care in hospital -greater than 10 day stay, within last 2-3  years, used an interpreter.

• Non-Spanish speaking.
• No leadership role or experience with complex care.
• < 18 years.

Eligibility Criteria:

• Moderate to severe central sleep apnea (AHI ≥ 15 events per hour) based on a sleep study scored by a local sleep laboratory. It is recommended that a patient have a PSG within 12 months of the expected implant date documenting moderate to severe CSA.
• Age 18 years or older.
• Signed Institutional Review Board (IRB)/Independent Ethics Committee (IEC) approved informed consent.
• In the opinion of the investigator, subject is willing and able to comply with the protocol.
• Not currently enrolled in another investigational study or registry that would directly interfere with the current study, except if the subject is participating in a mandatory government registry, or a purely observational registry with no associated treatments. Each instance should be brought to the attention of the sponsor to determine eligibility.
• In the opinion of the Investigator, life expectancy exceeds one year.
• The subject is not pregnant or planning to become pregnant.

• Adult 21 years and older.
• English speaking.
• Able to provide consent.
• Clinically diagnosed stable heart failure with NYHA Class I-III symptoms.

• Patients who are unable to engage in a regularly structured exercise training program.
• History of dangerous arrhythmias.
• BMI > 40 kg/m^2
• Current smokers or smoking history of > 20 pack years
• Pregnant women, implanted pacemaker and/or ICD, cochlear implants, drug infusion pump, or any other implanted metal objects.

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

• Healthy adults with no history of cardiac or respiratory related disease (no asthma).
• Nonsmoker.
• Similar demographics with USAF pilots – age ranges (20 to 50 years).
• BMI < 32 kg/m^2 – generally ovoid significant obesity although some variation in body habitus is good.
• Regularly active – no exercise limitations – orthopedic or other.

Exclusion Criteria:

• Age under 20 or over 50 years.
• Smoker.

• Liver cirrhosis of any etiology. Diagnosis of cirrhosis based on at least one of the following criteria:
  • Histology;
  • Imaging showing cirrhotic liver;
  • Elastography indicating cirrhosis
  • FibroTest result of F4;
  • Varices AND chronic liver disease;
  • Ascites AND chronic liver disease.
• Patient is scheduled for HCC surveillance according to standard of care (SOC) using abdominal ultrasound (US) and blood-based liver function tests (LFT).
• Age ≥ 18 years.
• Patient information received, read, understood, and signed.

• History of liver cancer.
• History of any other cancer.
• History of liver resection.
• History of solid organ transplant.
• Liver fibrosis < F4.
• Life expectancy is < 12 months.

Eligibility last updated 6/6/22. Questions regarding updates should be directed to the study team contact.

• Age ≥ 14 years old. Subjects speaking any language will be offered participation.
• Subjects capable of providing informed consent to the study. For those subjects younger than 18 years old who agree to participate in the study, informed consent will be obtained from patient’s parents/guardian.
• Subjects capable of performing pulmonary function test (PFT) maneuvers, as per pulmonary function test laboratory protocol.
• Patients will be enrolled through the Mayo Clinic Rochester Transgender and Intersex Specialty Care Clinic (TISCC), once patient has decided to undergo hormonal gender-affirming therapies (pubertal blockers, and masculinizing or feminizing hormone therapies).

• Subjects unable to provide consent, or subjects who do not agree to discuss the study with their parents/guardians.
• The presence of contraindications for pulmonary function testing including (these will be reviewed at the time of recruitment and prior to each spirometry associated with the study):
• Recent surgical procedures (< 3 months) that could be affected by lung function testing, including the following categories: Abdominal surgery, Eye surgery, Thoracic surgery, Ear surgery, Brain surgery, Vascular surgery. The presence of previously known respiratory disorders including pulmonary embolism (< 6 months), pleural effusion, pneumothorax, hemoptysis.
• Recent myocardial infarction (< 1 month), new cardiac arrythmia (< 3 months), recent cardiac pacemaker implantation (< 3 months).
• Heart failure symptoms, significant shortness of breath, tachycardia, or angina
• The presence of chronic pulmonary diseases that maybe associated with changes in pulmonary function overtime such as asthma, chronic obstructive pulmonary disease, or interstitial lung diseases.

Eligibility last updated 7/8/22. Questions regarding updates should be directed to the study team contact.

• Patients who have been seen at Mayo Clinic and have diagnosis of Hidradenitis Suppurativa (HS) and Psoriasis.

• Patient who are not able to understand and give consent.
• Patients whose records are incomplete.

Eligibility last updated 6/6/22. Questions regarding updates should be directed to the study team contact.

• All SCIMS participants following completion of their regularly scheduled Form II follow-up during the enrollment period for this module.

• SCIMS participants who do not complete their regularly scheduled Form II follow-up within the enrollment period for this module will not be included (e.g., lost to followup, declined to participate in the Form II follow-up, deceased).

Eligibility last updated 6/17/22. Questions regarding updates should be directed to the study team contact.

• Age ≥ 18 years
• Willing to provide samples at baseline.
• Cirrhosis
  •where Cirrhosis is defined as:
  • At least one liver biopsy within 5 years prior to consent showing either: a) Metavir stage 4 fibrosis; Ishak Stage 5-6 fibrosis; OR
• If no liver biopsy, the following imaging + laboratory criteria define cirrhosis for the purposes of this protocol:
  • Evidence on imaging, of stiffness, or of varices according to the MOP, AND;
  • Either: FIB-4 > 2.67 OR platelets < 150 (within 180 days prior to consent or during Screening).

• Known and documented prior or current hepatocellular carcinoma (HCC) or cholangiocarcinoma.
• Known transjugular intrahepatic portosystemic shunt (TIPS), balloon retrograde transvenous obliteration (BRTO) or porto-systemic shunt surgery regardless of time of occurrence.
• Known prior solid organ transplant or bone marrow transplant.
• Current participation in active medication treatment trials at the time of consent for LCN POST.
• Prisoners or individuals with more than 180 days incarceration pending due to difficulty with visits.
• Bariatric surgery in the last 180 days prior to consent.
• Known history of fontan procedure-associated liver disease (FALD).
• Known current medical or psychiatric conditions which, in the opinion of the investigator, would make the participant unsuitable for the study or interfere with or prevent follow-up per protocol.
• Current liver-unrelated end-stage organ failures (Dialysis, stage 3-4 congestive heart failure (CHF), current chronic obstructive pulmonary disease (COPD) on home oxygen, current known active malignancy besides non-melanomatous skin cancer or carcinoma in situ).
• Documented history of acute alcohol-associated hepatitis (according to NIAAA criteria as described in the MOP) in the 180 days prior to consent.
• Documented current or continued signs and symptoms of acute Wilson disease (acute liver failure, acute neurological deficits, hemolysis).
• In patients with primary sclerosing cholangitis (PSC): Current active cholangitis with 90 days prior to consent.
• Documented cardiac cirrhosis.
• Known recent (within the last 365 days) or present hepatic decompensation with ascites/hydrothorax, hepatic encephalopathy or variceal bleeding.
• Known or documented habitual non-adherence to previous research studies or medical procedures or unwillingness to adhere to protocol (e.g., unwilling to obtain consent or samples).
• Current model for end-stage liver disease (MELD) cut off ≥ 15*.
• Current Child-Turcotte-Pugh (CTP) B or C*.
• Current known Hepatitis C Virus (HCV) without sustained virologic response (SVR).
• Current known quantifiable Hepatitis B Virus (HBV) viral DNA on therapy with ongoing adherence on suppressive therapy*.
• In patients with autoimmune hepatitis: serum aspartate aminotransferase (AST) > 2X upper limit of normal (ULN) within 60 days prior to consent or during Screening*.
• In patients living with HIV: CD4+ T cell count less than 100 cells/mm3 within 60 days prior to consent or during Screening*.

*Indicates an exclusion criterion that may depend on laboratory results and other clinical assessments to be ordered during Screening after confirming the participant is otherwise eligible. If the test was performed as standard-of-care in the 60 days prior to consent, it does not need to be re-done for eligibility.  

Eligibility last updated 7/18/22. Questions regarding updates should be directed to the study team contact.

• Male and female subjects between the ages of 18 and 70 years, inclusive, at Screening.
• Body mass index (BMI) of ≥ 25 and < 40 kg/m^2 with a total body weight 50-150 kg (inclusive) at Screening and Day 1 Pre-dose.
• Suspected or confirmed diagnosis of noncirrhotic NAFLD/NASH with no fibrosis to moderate fibrosis (stages F0-F2) by one of the following:
  • Histologically with liver biopsy within 2 years prior to Screening (documentation with pathology report); or
  • Radiologically with ≥ 5% steatosis measured by magnetic resonance imaging-derived proton density fat fraction (MRI-PDFF), or controlled attenuation parameter (CAP?) > 288 dB/m via FibroScan® assessment or presence of hepatic steatosis on abdominal ultrasound; and an increased serum alanine aminotransferase (ALT) > 30 U/L within 1 year prior to Screening; or
  • Clinically with a diagnosis of Metabolic Syndrome (MetS) reflecting the presence of at least 3 of 5 factors/criteria (i.e., abdominal obesity, elevated triglycerides, reduced HDL-C, elevated blood pressure, and/or elevated fasting glucose [IFG or type 2 diabetes mellitus]) as defined by the National Cholesterol Education Program's Adult Treatment Panel III (NCEP ATP III) [Grundy 2005]; and seronegative hepatitis B and C; and fatty liver on imaging within 1 year prior to Screening.

• History or presence of cirrhosis by any diagnostic measure (clinical, imaging, histopathology, or laboratory).
• Evidence of decompensated liver disease (laboratory or clinical abnormalities-ascites, variceal bleeding, etc.).
• History or presence of other concomitant liver disease (eg, hepatitis B & C, alcoholic liver disease, autoimmune liver disease, primary biliary cirrhosis, primary sclerosing cholangitis, hemochromatosis, Wilson's disease, alpha-1 antitrypsin (A1AT) deficiency, bile duct obstruction, liver primary or metastatic cancer, drug-induced liver disease.

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

Eligibility last updated 5/8/23. Questions regarding updates should be directed to the study team contact.

• Mayo Clinic patients scheduled for or being seen in the Healthy Longevity Clinic in the Division of General Internal Medicine.
• 18 years of age or older at time of consent
• Have the ability to provide informed consent
• Have the ability to complete all aspects of this trial.

• < 18 years of age. 

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.

• Females, 18 to 35 years of age (pregnancy assessed by self-report).
• Non-pregnant.

• Male.
• Known pregnancy (by self-report.
• Known genetic disorder (by self-report).
• Cancer history (including any form of skin cancer).
• Diabetes.
• Failure to meet 21 CFR 1271 donor eligibility criteria based on responses to a donor eligibility questionnaire.
• Positive infectious disease result on any test in the infectious disease screening panel (including HBsAg Screen, HBc Total Ab, HBV NAT, HCV NAT, HIV-1 NAT, HCV Ab Screen, HIV-1/-2, plus O Ab Screen, HTLV-I/-II Ab Screen, T. cruzi Total Ab, Syphilis Ab Screen, CMV Total Ab, West Nile Virus NAT).
• Medical records review.
• Physical exam.    

Eligibility last updated 1/12/23. Questions regarding updates should be directed to the study team contact. 

• Age ≥ 18 years.
• Patients with histologically or cytologically confirmed advanced or metastatic non-neurological solid tumors, who have no curative or life prolonging therapeutic options AND a minimal level of tumor staining for PDL1 (clinical test using 22c3 immunohistochemistry) demonstrating tumor staining in ≥ 1% of tumor cell.
• At least one prior systematic therapy in the metastatic setting (adjuvant or neoadjuvant therapy not included);
  • NOTE: There is no upper limit to the number of prior treatment regimens.
• ECOG Performance Status (PS) 0, 1 or 2.
• The following laboratory values obtained ≤ 14 days prior to registration:
  • Hemoglobin ≥ 9.0 g/dL (patients may be transfused to meet Hgb requirement);
  •  Absolute neutrophil count (ANC) ≥ 1500/mm^3;
  • Platelet count ≥ 100,000/mm^3;
  • Total bilirubin ≤ 1.5 x ULN or direct bilirubin ≤ 0.4 mg/dL;
  • SGOT (AST) ≤ 2.5 x ULN or ≤ 5 x ULN in case of liver metastases;
  • Alkaline phosphatase ≤ 2.5 x ULN or ≤ 5 x ULN in case of liver metastases;
  • Calculated creatinine ≤ 1.5 x ULN or Calculated creatinine clearance ≥45 ml/min using the Cockcroft-Gault formula below for subjects with creatinine >1.5 ULN:
    • Creatinine clearance for males = (140
      •age) (weight in kg) (72) (serum creatinine in mg/dL);
    • Creatinine clearance for females = (140
      •age) (weight in kg) (0.85) (72) (serum creatinine in mg/dL).
• Negative serum pregnancy test done ≤ 7 days prior to registration, for women 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.
• No motor peripheral neuropathy.
• Sensory peripheral neuropathy ≤ Grade 1 (per CTCAE 5.0).
• Immune-related adverse events (irAEs) from prior treatment have returned to baseline or ≤ Grade 1.
• For persons of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use a contraceptive method with a failure rate of < 1% per year during the treatment period and for 6 months after the last dose of study treatment.
• For person able to father a child: agreement to remain abstinent (refrain from heterosexual intercourse with a person of childbearing potential) or use contraceptive measures, and agreement to refrain from donating sperm during the treatment period and for 6 months after the last dose of study treatment.
• Willingness to provide mandatory blood specimens for correlative research.
• Willingness to provide mandatory tissue specimens for correlative research.
• Willing to return to enrolling institution for follow-up 2-4 weeks after treatment discontinuation.
• Life expectancy ≥ 90 days (3 months).

Inclusion Criteria Specific to Dose Expansion Cohorts

• NOTE: Melanoma Dose Expansion cohort only planned for now. Availability to add other disease-specific Dose Expansion cohorts possible in future protocol amendments.
• For Dose Expansion Cohort:
  • Measurable disease defined as at least one lesion whose longest diameter can be accurately measured as ≥ 2.0 cm with chest x-ray, or as ≥ 1.0cm with CT scan or MRI scan; or CT component of a PET/CT;
    • NOTE: Disease that is measurable by physical examination only is not eligible.
• Melanoma Dose Expansion Cohort:
  • Histologic proof of surgically unresectable stage IV malignant melanoma;
  • Disease progression on or after anti-PD1/PDL1 antibody-based therapy in the metastatic setting (adjuvant or neoadjuvant therapy with anti-PD1/PDL1 antibody do not count).

Exclusion Criteria

• Any of the following because this study involves an investigational agent whose genotoxic, mutagenic, and teratogenic effects on the developing fetus and newborn are unknown:
  • Pregnant persons;
  • Nursing persons;
  • Persons of childbearing potential {and persons able to father a child} who are unwilling to employ adequate contraception.
• Known standard therapy for the patient’s disease that is potentially curative or definitely capable of extending life expectancy.
• Any anti-cancer therapy or investigational agents ≤- 4 weeks prior to registration.
• Failure to recover from prior surgery.
• Failure to fully recover from acute, reversible effect of prior chemotherapy regardless of interval since last treatment.
• Anti-PD(L)1 antibody ≤ 4 weeks prior to registration.
•  Previous grade 4 irAEs from immune checkpoint inhibitor antibody therapy.
• Co-morbid systemic illnesses or other severe concurrent disease 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.
•  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;
  • symptomatic congestive heart failure;
  • unstable angina pectoris;
  • cardiac arrhythmia;
  • or psychiatric illness/social situations that would limit compliance with study requirements.
• Other medical conditions including be not limited to:
  • History of liver disease such as cirrhosis, chronic active hepatitis, chronic persistent hepatitis or hepatitis B or C;
  • Active infection requiring parenteral antibiotics;
  • Active tuberculosis or active, non-infectious pneumonitis;
  • Evidence of interstitial lung disease;
  • New York Heart Association class II-IV congestive heart failure (Serious cardiac arrhythmia requiring medication);
  • Myocardial infarction or unstable angina ≤ 6 months prior to registration;
  • Congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias.
• Active autoimmune disease such as Crohn’s disease, rheumatoid arthritis, Sjögren’s disease, systemic lupus erythematosus, or similar conditions requiring systemic therapy within the past 2 years with the use of disease modifying agents, corticosteroids, or immunosuppressants or a documented history of clinically severe autoimmune disease/syndrome difficult to control in the past;
  •               EXCEPTIONS (the following are allowed):
    • Vitiligo or resolved childhood asthma/atopy;
    • Intermittent use of bronchodilators or local steroid injections;
    • Non-immunosuppressive maintenance treatments in the setting of clinically asymptomatic disease (e.g., sulfasalazine for ulcerative colitis);
    • Hypothyroidism or hypoadrenalism, stable on hormone replacement;
    • Diabetes stable with current management;
    • History of positive Coombs’s test but no evidence of hemolysis;
    • Psoriasis not requiring systemic treatment;
    • Conditions not expected to recur in the absence of an external trigger;
    • Secondary adrenal insufficiency from previous hypophysitis, currently on physiologic replacement steroid dosing only.
•  Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm.
• Other active malignancy ≤ 3 years prior to registration. Patients must not be receiving chemotherapy or immunotherapy for another cancer. Patients must not have another active malignancy requiring active treatment:
  • EXCEPTIONS: Non-melanotic skin cancer or carcinoma-in-situ of the cervix:
    • NOTE: If there is a history of prior malignancy, they must not be receiving other specific treatment;
    • NOTE: Early-stage cancer (stage 1/2, treated) should be allowed.
• History of myocardial infarction ≤ 6 months, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias.
• Active CNS metastasis;
  • NOTE: Patients with prior brain metastases that are asymptomatic without corticosteroid use and stable or improved ≥30 days after treatment with surgery or radiation are not excluded.
• Corticosteroid use ≤ 14 days prior to registration;
  • NOTE: Patients must be off systemic corticosteroids for at least 2 weeks prior to registration. This includes oral or IV route of administration. Patients on chronic corticosteroids for adrenal insufficiency or other reasons may enroll if they receive less than 10 mg/day of prednisone (or equivalent). Patients receiving inhaled or intranasal or intra-articular steroids are not excluded;
  • EXCEPTIONS: Patients requiring steroid premedication for radiology contrast allergy are not excluded.

• Age 21-65.
• BMI ≥ 30 and ≤ 40 kg/m² .
• Willingness to comply with the substantial lifelong dietary restrictions required by the procedure.
• History of failure with non-surgical weight-loss methods.
• Willingness to follow protocol requirements, including signed informed consent, routine follow-up schedule, completing laboratory tests, and completing diet counseling. 
• Residing within a reasonable distance from the investigator’s office and able to travel to the investigator to complete all routine follow- up visits.
• Ability to give informed consent.
• Women of childbearing potential (i.e., not post-menopausal or surgically sterilized) must agree to use adequate birth control methods. 

• History of foregut or gastrointestinal (GI) surgery (except uncomplicated cholecystectomy or appendectomy).
• Prior gastrointestinal surgery with sequelae; i.e., obstruction, and/or adhesive peritonitis or known abdominal adhesions.  
• Prior open or laparoscopic bariatric surgery.  
• Prior surgery of any kind on the esophagus, stomach or any type of hiatal hernia surgery. 
• Any inflammatory disease of the gastrointestinal tract including severe (LA Grade C or D) esophagitis, Barrett’s esophagus, gastric ulceration, duodenal ulceration, cancer or specific inflammation such as Crohn’s disease.  
• Potential upper gastrointestinal bleeding conditions such as esophageal or gastric varices, congenital or acquired intestinal telangiectasis, or other congenital anomalies of the gastrointestinal tract such as atresias or stenoses. 
• Gastrointestinal stromal tumors, history of premalignant gastric lesions (intestinal metaplasia), history of familial and nan-familial adenomatous syndromes.  
• A gastric mass or gastric polyps > 1 cm in size.  
• A hiatal hernia > 4cm of axial displacement of the z-line above the diaphragm or severe or intractable gastro-esophageal reflux symptoms.  
• A structural abnormality in the esophagus or pharynx such as a stricture or diverticulum that could impede passage of the endoscope.  
• Achalasia or any other severe esophageal motility disorder.
• Severe coagulopathy. 
• Insulin-dependent diabetes (either Type 1 or Type 2) or a significant likelihood of requiring insulin treatment in the following 12 months or a HgbA1C ≥ 9. 
• Subjects with any serious health condition unrelated to their weight that would increase the risk of endoscopy.
• Chronic abdominal pain.
• Motility disorders of the GI tract such as gross esophageal motility disorders, gastroparesis or intractable constipation. 
• Hepatic insufficiency or cirrhosis.
• Use of an intragastric device prior to this study due to the increased thickness of the stomach wall preventing effective suturing.  
• Active psychological issues preventing participation in a life-style modification program as determined by a psychologist.
• Patients unwilling to participate in an established medically supervised diet and behavior modification program, with routine medical follow-up.  
• Patients receiving daily prescribed treatment with high dose aspirin (> 80 mg daily), anti-inflammatory agents, anticoagulants or other gastric irritants.  
• Patients who are unable or unwilling to take prescribed proton pump inhibitor medication.
• Patients who are pregnant or breast-feeding.  
• Patients currently taking weight-loss medications or other therapies for weight loss within the prior 6 months. 
• Subjects with severe cardiopulmonary disease or other serious organic disease which might include known history of coronary artery disease, myocardial infarction within the past 6 months, poorly controlled hypertension, required use of NSAIDs.
• Subjects taking medications on specified hourly intervals that may be affected by changes to gastric emptying, such as anti-seizure or anti-arrhythmic medications.
• Subjects who are taking corticosteroids, immunosuppressants, and narcotics.
• Symptomatic congestive heart failure, cardiac arrhythmia or unstable coronary artery disease.  
• Pre-existing respiratory disease such as moderate or severe chronic obstructive pulmonary disease (COPD) requiring steroids, pneumonia or cancer.  
• Diagnosis of autoimmune connective tissue disorder (e.g. lupus, erythematous, scleroderma) or immunocompromised.  
• Specific diagnosed genetic disorder such as Prader Willi syndrome. 
• Eating disorders including night eating syndrome (NES), bulimia, binge eating disorder, or compulsive overeating. 
• Known history of endocrine disorders affecting weight such as uncontrolled hypothyroidism. 
• If deemed medically inappropriate or ineligible by investigator. 

Eligibility last updated 2/1/22. Questions regarding updates should be directed to the study team contact.

• Subject is 18 years or older at the time of the procedure.
• Pulmonary nodule biopsy attempted/performed using the Ion Endoluminal System and Cios Spin 3D imaging.
• Pulmonary nodule ≤ 2 cm in largest diameter.
• Subject able to understand and adhere to study requirements and provide informed consent.

• Planned lymph node staging performed before nodule biopsy.
• Nodule is a pure ground glass opacity.
• Plan to biopsy multiple nodules.

Eligibility last updated 11/29/22. Questions regarding updates should be directed to the study team contact.

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

Eligibility last updated 6/29/23. Questions regarding updates should be directed to the study team contact.

• Age 18 years and older.
• Scheduled to undergo nasal endoscopy

• Cystic fibrosis.
• Cigarette smoking in the last 6 months.
• Common Variable Immunodeficiency Disease.
• EGPA or small vessel vasculitis.
• Primary ciliary dyskinesia.
• Primary immune deficiency disorder.
• Treatment with antibiotics within the past 4 weeks before visit.
• Oral corticosteroids in the past 2 weeks before visit.
• Intramuscular corticosteroids in the past 6 weeks before visit.
• Current cancer treatment with immunotherapy and chemotherapy.
• Treatment with biologics or zileuton.

• Age ≥ 18 years.
• Primary total knee arthroplasty.
• Patients staying at least one night in the hospital after surgery.

• Individuals < 18 years.
• Same day discharge.
• Revision or partial total knee arthroplasty.
• Corticosteroid use within 3 months prior to surgery.
• Inflammatory arthritis
• Current systemic fungal infection.
• Renal or liver failure.
• Prior adverse reaction to corticosteroid.
• Primary TKA requiring hardware removal.

Subjects must satisfy all following criteria at the Screening visit unless otherwise stated:

• Male or female aged 18 years or older.
• Able to provide written informed consent.
• Active and consistent cortisol excess:
  This is defined as having a consistently elevated UFC in patients newly diagnosed
  with Cushing’s or in patients with recurrent or refractory Cushing’s disease having
  high-normal UFCs or both of the other guideline-recommended tests (overnight
  dexamethasone suppression or late-night/bedtime salivary cortisol) being consistent
  with cortisol excess:
  • Urinary free cortisol (UFC) > upper limit of normal (ULN) based on at least 2
    valid (i.e., complete) 24-hour urine samples collected during Screening. The subjects will be provided collection devices for three 24--hour collections to ensure 2 complete collections are received, particularly if a subject requires washout of other cortisol -suppressing agents. If more than 2 valid collections
    are received; the mean of all valid completed collections collected after completion of the washout period (if applicable), and available at Day 1 must
    be > ULN, as confirmed by the central laboratory. Should an additional, otherwise disqualifying, UFC value become available only after Day 1
    randomization, the subject will be allowed to continue planned treatment and a sensitivity, per-protocol analysis will be conducted.
• Overnight dexamethasone suppression testing to minimally include a non-suppressed morning serum cortisol ≥ 1.8 mcg/dL (50 nmol/L) after 1 mg ONDST within the last year. Testing should be confirmed by concurrent dexamethasone level adequate to provide suppression. Individuals using estrogen should meet further criteria accounting for potential increased
  corticosteroid binding globulin (CBG); e.g., free cortisol > 80 ng/dL (2.2 nmol/L), total serum cortisol ≥ 5 mcg/dL (138 nmol/L), or correction based on CBG measurement. If ONDST dates or results are not available for
  tests performed within the past year, ONDST with dexamethasone level should be repeated to confirm eligibility and should use local laboratory results.
• Late-night/bedtime salivary cortisol above ULN based on at least 2 adequate samples collected during Screening using local laboratory results.
• Documented diagnosis of ACTH-dependent Cushing’s syndrome:
  • This includes Cushing’s disease, ectopic ACTH secretion, and ectopic CRH secretion.
    Subjects may include newly diagnosed subjects who have declined or are not considered candidates for surgery or subjects with residual or recurrent disease after 
    surgery in whom surgery or radiation are not planned within the next 6 months.
  • Previous medical records will be used to support the diagnosis. At least 1 of the following will be considered satisfactory to establish the diagnosis:
  • History of positive ACTH-staining pathology;
  • History of documented, transient, AI after tumor removal requiring
    glucocorticoid replacement;
  • ACTH level > 20 pg/mL with positive ACTH or cortisol response to CRH or desmopressin (DDAVP) stimulation in the presence of hypercortisolemia;
  • Inferior petrosal sinus sampling with ACTH central: plasma gradient ≥ 2 before CRH or DDAVP or ≥ 3 after CRH or DDAVP;
  • Presumptive Cushing’s disease based on presence of a pituitary tumor ≥ 6 mm along with positive ACTH or cortisol response to CRH or DDAVP stimulation
    or an overnight or high-dose (8 mg) dexamethasone suppression of cortisol, performed and interpreted according to locally recognized standards of
    diagnosis;
  • In the absence of any of the above, an individual might be eligible if ectopic ACTH-dependent Cushing’s syndrome was otherwise confirmed via adequate testing consistent with the local standards of care. Such cases must be discussed with and explicitly approved by the Medical Monitor and Sponsor,
    and the specific diagnostic criteria used to establish the diagnosis of ACTH-dependent Cushing’s syndrome must be documented. 
• Willing to comply with reproductive precautions: Females will not be pregnant or lactating, and females of childbearing potential and males will agree to use contraception.
• Current evidence of Cushing’s comorbidities of hyperglycemia, dyslipidemia, hypertension, or osteopenia:
  • Defined by having at least 1 of the below criteria, ideally including both or either of “a” and “b”, but including any of “a”, “b”, “c”, or “d”;
  • Diagnosis of insulin-resistance/pre-diabetes or type 2 diabetes:
  • Including subjects on stable diabetic treatment but excluding those ethically requiring further or frequent therapy adjustments. Type 2 diabetes is defined as a current HbA1c ≥ 6.5% but ≤ 9.5% (otherwise excluded), fasting blood glucose (FBG) > 126 mg/dL, or 2-hour OGTT ≥ 200 mg/dL. Pre-diabetes is defined as current HbA1c < 6.5% but > 5.7%, FBG > 100 to 125 mg/dL, or 2-hour OGTT 140 to 199 mg/dL. Insulin-resistance may also be defined by abnormal HOMA-IR > 2.5 or by CGM data (e.g., mean glucose, glycemic variability, time in range, estimated HbA1c).
  • Diagnosis of dyslipidemia:This is evidenced by history of total cholesterol level of ≥ 6.2 mmol/L (240 mg/dL) or triglycerides of ≥ 5.2 mmol/L (200 mg/dL). Current total cholesterol may be < 6.2 mmol/L, and current triglycerides may be < 5.2 mmol/L, if controlled with allowed lipid-lowering therapy;
  • Diagnosis of hypertension: 
  • Incident hypertension should be brought under control and stabilized prior to randomization at Day 1. Subjects with hypertension, which is reasonably, but sub-optimally managed by standard therapy at baseline (systolic blood pressure [SBP] >140 but < 180 or DBP > 90 but < 120 mmHg) qualify;
  • Diagnosis of osteoporosis or osteopenia:
  • Osteopenia (T-score ≤ -1.0 or Z-score ≤ -2.0) or osteoporosis as determined previously, during the site’s local Baseline DEXA reading, or history or evidence of minimal-traumatic or osteoporotic fracture treated with lifestyle modification with mineral or vitamin supplementation or stable approved osteoporosis therapies. 

Subjects will be excluded from the study if they satisfy any of the following criteria at the Screening visit unless otherwise stated:

• Recent or planned Cushing’s surgery:
• Surgery for Cushing’s within the past 6 weeks or planned within 6 months after randomization.
• Use of medications for Cushing’s syndrome within the washout periods prior to randomization.
• Recent Cushing’s radiotherapy:
• A history of radiation therapy for Cushing’s within a period prior to plateau of efficacy (typically within the past 2 years of intensive targeted therapy [e.g., stereotactic radiation] or within 4 years of more conventional radiation therapy).
• History of bilateral adrenalectomy.
• History of pseudo-Cushing’s syndrome.
• History of cyclic Cushing’s syndrome.
• Exogenous hypercortisolism or factitious Cushing’s syndrome.
• History of non-ACTH-dependent hypercortisolism:
• This includes disease caused by a known inherited syndrome (e.g., McCune Albright syndrome, Carney complex) but not including multiple endocrine neoplasia type 1 where diagnostic testing has led to a diagnosis of Cushing’s disease (79%) while excluding autonomous adrenal Cushing’s syndrome (21%).
• High risk of acute morbidity from corticotroph adenoma growth: (similar to that which occurs with Nelson’s syndrome) defined as:
• Current evidence of macroadenoma with, or at risk of impingement on vital structures. For example, tumor showing aggressive growth abutting or compressing the optic chiasm or with evidence of blood-vessel encroachment, encirclement, invasion, or compression.
• Uncontrolled Cushing’s comorbidities of hyperglycemia, dyslipidemia, hypertension, or osteopenia:
• Including evidence of chronic, poor glycemic control (HbA1c > 9.5%), symptomatic dyslipidemia (e.g., hypercholesterolemia with recent (< 1 year) cerebro- orcardiova scular events, hypertriglyceridemia with pancreatitis), persistent uncontrolled hypertension (systolic blood pressure > 180 mmHg or DBP > 120 mmHg), or recent (< 1 year) osteoporotic fracture ethically requiring additional medical intervention.
• Use of drugs likely to interfere with study assessments:
• These include chronic systemic corticosteroids, thiazolidinediones, drugs that may alter the metabolism and clearance of corticosteroids (e.g., 5-alpha-reductase inhibitors), supplements or traditional medicines that contain a HSD-1 inhibitor, within 12 weeks prior to the first dose of study drug. 
• Uncontrolled hypothyroidism or hyperthyroidism:
• For patients with a history of, or treatment for, abnormal thyroid function, free thyroxine (T4) should be in normal range and stable, whether endogenous or on levothyroxine replacement [> 8 weeks]. Thyroid-stimulating hormone (TSH) will often not be reliable in post-operative patients, but if measured, should not be significantly elevated. Locally obtained recent, (within 3 months of screening) T4 and TSH results may be used for screening evaluation. If central laboratory data are not available, or delayed, these labs may be obtained locally during the screening period.
• Moderate or severe renal impairment:
• Defined by an estimated glomerular filtration rate (GFR) repeatedly < 60 mL/min/1.73 m^2  or confirmed by measured GFR < 60 mL/min/1.73 m^2.
• In the long-term phase of study, patients having function decline to < 45 mL/min/1.73 m^2 should be withdrawn from the study unless formal renal-impairment studies support safe continuation.
• Medically significant liver disease Including cirrhosis, chronic active hepatitis, chronic persistent hepatitis, or subjects with serum total bilirubin > 1.5 × ULN (unless previously diagnosed with benign Gilbert’s disease) or serum ALT or AST > 3 × ULN.
• Medically significant cardiovascular or ECG abnormalities: 
• This includes subjects with recent (< 1 year) myocardial infarction or stroke, orthostatic or vasovagal syncope, QT interval corrected (QTc) intervals > 500 msec, or evidence of significant, life-threatening arrhythmia or bradycardia (HR < 45 bpm).
• History of idiopathic thrombocytopenic purpura.
• History of adrenal carcinoma.
• Recent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection:
• Positive test for infection within the past 4 weeks or hospitalization for coronavirus disease 2019 (COVID-19) within the past 6 months.
• History of cancer within 3 years other than ectopic ACTH from an unidentified source, with plans for therapy, intervention (e.g., biopsy), or likelihood for recurrence is likely to interfere with or confound the results of this trial. If stable and requiring hormone-suppressive therapy, subjects with breast, prostate, bone, or other endocrine cancer may be included at Medical Monitor discretion, however their data may be excluded in assessment of SPI-62 effects on HPA and HPG axis biomarkers).
• Any major surgery, or significant post-operative sequelae, within 1 month prior to informed consent or planned during the trial.
• Pregnant, lactating, or planning fertility in the next 6 months and unwilling to adhere to approved contraceptive use or abstinence.
• Participation in any clinical trial within 30 days or 5 half-lives, whichever is longer, prior to informed consent (or longer for biologic and long-lasting experimental therapies).
• Receipt of blood products within 2 months prior to Screening.
• Donation of blood from 3 months prior to Screening, plasma from 2 weeks prior to Screening, or platelets from 6 weeks prior to Screening. Subjects are not to donate blood, plasma, or platelets during the study.
• Poor peripheral venous access.
• Any other current or prior medical condition expected to interfere with the conduct of the study or the evaluation of its results. 

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

Eligibility last updated 8/28/23. Questions regarding updates should be directed to the study team contact.

• Patient or legal representative voluntarily agreed to participate by signing and dating the written informed consent form after trial has been fully explained.
• Patient 18 years of age or older.
• History of recurrent CDI.
• Current active qualifying CDI episode.
• Females (assigned at birth) must fulfill at least 1 of the following criteria: 
• Postmenopausal, defined as amenorrhea ≥ 1 year; or 
  • Surgically sterile: hysterectomy, bilateral oophorectomy, or tubal ligation; or 
  • Abstinent or willing to use adequate contraception from Screening through the week 24 visit.
• Males (as assigned at birth) must fulfill the following criteria:
  • Abstinent or willing to use adequate contraception from Screening through the Week 24 visit.

• Known stool samples testing positive for enteric pathogens (e.g., Salmonella, Shigella, diarrhoeagenic E. coli, Campylobacter, Giardia) within 28 days prior to Screening.
• Inability to ingest capsules (e.g., severe nausea, vomiting, gastroparesis, gastric outlet obstruction, dysphagia and/or history of chronic aspiration).
• Active or suspected ileus, toxic megacolon, or bowel obstruction.
• Historical or current diagnosis of inflammatory bowel disease (e.g., Crohn’s disease, ulcerative colitis, indeterminate colitis, or microscopic colitis).
• Recent diagnosis (< 6 months prior to Screening) of diarrhea-predominant irritable bowel syndrome (post-infection or not related to an enteric infection). Patients with diarrhea-predominant irritable bowel syndrome ≥ 6 months prior to Screening may be randomized following confirmation of eligibility.
• Current diagnosis of chronic diarrheal illness with pre-CDI baseline diarrhea. This includes but is not limited to celiac disease, bile salt diarrhea, chronic pancreatitis, and short gut syndrome.
• Past administration of bezlotoxumab (Zinplava™), or past enrollment in a C. difficile vaccine trial within 12 months prior to Randomization.
• Participation in PRISM3 (CDI-001) or PRISM-EXT (CP101-CDI-E02) or received CP101 at any time in the past.
• Fecal transplant or other live microbiome therapeutics for any condition, regardless of route of administration within 12 months prior to Randomization.
• Initiation of any systemic cancer treatment (e.g., chemotherapy, radiotherapy, biologic, immunotherapy, others) for active malignancy that is planned 8 weeks prior to Randomization or during the 8 weeks following Randomization. Patients on maintenance treatment for malignancy may be randomized following confirmation of eligibility.
  • NOTE: Patients on hormone therapy alone are eligible.
• Known primary or secondary immunodeficiency, including but not limited to, IgA deficiency, common variable immunodeficiency, severe combined immunodeficiency, or human immunodeficiency virus/acquired immune deficiency syndrome.
• History of solid organ transplantation or stem cell transplant.
• Initiation or dose escalation of systemic immunosuppressive agents, at the discretion of the Investigator, for any condition during the 8 weeks prior to Randomization or planned during the 8 weeks following Randomization. Examples may include but are not limited to corticosteroid agents given orally or intravenously, cyclosporine, tacrolimus, or tumor necrosis factor inhibitors. Patients on stable low dose of systemic immunosuppressive agents or short courses (< 2 weeks) may be randomized following confirmation of eligibility.
• Major intra-abdominal surgery (e.g., bowel resection) within the past 60 days prior to Screening (excluding appendectomy or cholecystectomy)and/or planned invasive surgery/hospitalization during the trial.
• History of total colectomy or ileostomy.
• Use of a systemic antibiotic for any condition (other than CDI) during the Screening period, or any anticipated use of a systemic antibiotic for any condition other than CDI during the trial for 8 weeks after Randomization. This includes patients who have a known medical procedure that requires antibiotic prophylaxis (e.g., elective surgical procedure or dental procedure requiring prophylactic antibiotics) scheduled during the trial.
• Active drug, chemical, or alcohol dependency as determined by the Investigator through history or optional toxicology screen.
• Enrollment in any other investigational drug, device, or observational trial within 30 days or 5 half-lives of the last dose, prior to Randomization (Day 1) or at any time during this trial.
• Pregnant, breast-feeding, or planning to become pregnant during the trial.
• Clinically significant abnormal laboratory values including, but not limited to, white blood cell count ≥ 15 × 10^9/L, absolute neutrophil count of < 1 × 10^9 neutrophils/L, or laboratory evidence of acute kidney injury at Investigators discretion, at Screening.
• Screening nasopharyngeal PCR test is positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
• Any acute, chronic, or unstable medical comorbidity, psychiatric, social, or other circumstances that, in the opinion of the Investigator, may interfere with trial compliance, completion, or accurate assessment of trial outcomes/safety. Examples include but not limited to acute myocardial infarction, acute stroke, uncompensated congestive heart failure, or decompensated liver disease.
  • NOTE: Trial patients may be screened while an inpatient in an acute care facility/hospital but must be discharged from inpatient medical admission prior to Randomization.
• Life expectancy < 24 weeks.
• Known hypersensitivity to CP101 or any component of its formulation or history of severe adverse reactions or other common drug class effects during prior exposure to similar compounds per the judgment of the investigator.

Eligibility last updated 2/1/22. Questions regarding updates should be directed to the study team contact.

• Women age 18-44 years of age.
• Undergoing autologous IVF planning for monitoring at Mayo Clinic Rochester with an antagonist or long luteal protocol, planned fresh embryo transfer, conventional or ICSI insemination with ejaculate sperm.

• Women undergoing donor oocyte, donor embryo cycles, oocyte cryopreservation cycles, planned freeze all, TESE or micro TESE sperm.
•  Patients undergoing cycles for fertility preservation, minimal stimulation in 
  vitro fertilization, or with planned cleavage stage embryo transfer

Eligibility last updated 10/11/22. Questions regarding updates should be directed to the study team contact.

• Invasive breast cancer with radiographic and/or clinical evidence of advanced metastatic or unresectable disease 2 ER+/HER2- patients prior to starting 2nd line therapy or beyond in the metastatic setting OR ER/PR/HER2-negative (Triple Negative) patients prior to starting any line of therapy in the metastatic setting.
• Note: ER/PR/HER2 status is defined per the 2018 ASCO/CAP guidelines as follows: ER-positive and PR-positive is defined as ≥ 1% reactive cells by immunohistochemical staining. HER2 Negative Disease is defined by meeting one of the following criteria:
  • 0 or 1+ by IHC and not amplified by ISH;
  • 0 or 1+ by IHC and ISH not done;
  • 2+ by IHC and ISH results are:
    • < 6.0 HER2 signals/cell with HER2/CEP17 ratio < 2.0;
  • IHC not done and not amplified by ISH.
• Measurable and/or non-measurable disease is allowed.
• Male or female breast cancer is allowed.
• Age > 18 years.
• Willingness to provide mandatory blood specimens.
• Willing to return to enrolling institution for follow up imaging at least once.

• Life expectancy of ≤ 6 months.
• Inability to provide blood samples based on the judgment of the treating provider.

Eligibility last updated 12/20/23. Questions regarding updates should be directed to the study team contact.

Inclusion Criteria;

• Pre-menopausal (21
  •50 years of age).
• Study group will consist of women seeking hysterectomy for possible adenomyosis adenomyomectomy.
• Controls will consist of women seeking hysterectomy for uterine prolapse or pelvic pain or transgender men prior to androgen treatment and whose pathology shows a uterus < 100 grams with no evidence of adenomyosis, endometriosis, or leiomyomas.

• No ua\se of GnRH analogues, aromatase inhimitors, selective E2 or P4 receptor modulators, oral contraceptives, or immunotherapy within 3 months prior to surgery in any patient.
• No history /confirmation or suspicion of autoimmune disease, fibromyalgia, endometriosis, or leiomyomas in any patient.
• No current or previous history of STDs, pelvic inflammatory disease, endometrial/cervical cancer in any patient.
• Women who do not exhibit menstrual cycles.

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

• Adult (18+) male and female subjects.
• Carry a diagnosis of epilepsy.
• Able to provide consent.
• Have a reliable home wifi service provider.
• Have a smartphone.
• Able to independently (or with help from a family member) complete the directions to self-install the device and ship it back at time of study completion.

• Subjects who are pregnant or may be pregnant.
• Pediatric patients (< 18 years of age).
• Subjects unable or unwilling to undergo remote monitoring using the Emerald device.
• Lack capacity to consent for self.
• Subjects who plan to have more than one additional person in the room with them during nocturnal hours (10 pm – 6 am).

Eligibility last updated 5/6/22. Questions regarding updates should be directed to the study team contact.

• Adults, ≥ 18 years of age.
• Waitlist active, temporarily inactive, and deferred adult lung transplant candidates from Mayo Clinic Florida; Mayo Clinic Rochester; or UW Medicine.

• Children < 18 years old.
• Patients who are non-verbal, non-English speakers, or extremely hard-of-hearing.