• Adult patients ≥ 18 years old.
• Diagnosed with plasma cell disorders.

• Children < 18 years old.
• Pregnant females.

Eligibility last updated 5/2/22. Questions regarding updates should be directed to the study team contact.

• 18 years of age or greater.
• Fluent English speakers.
• Medically cleared to play ice hockey.

• An allergy to the ingredients of Synaquell or Synaquell+ (Magnesium, beta hydroxybutyrate, Glutathione, N-acetyl-L-cysteine, Riboflavin, Magnesium, Leucine,
• Isoleucine, Valine, Resveratrol, Curcumin Phytosome, Nicotinamide riboside,
• Docosahexanoic Acid).
• Clinically documented hearing issues.
• In-ear hearing aid or cochlear implant.
• Implanted pacemaker or defibrillator.
• Metal or plastic implants in skull.
• Lack of verbal fluency in the English language.
• History of seizures.
• Allergy to rubbing alcohol or EEG gel.
• Unhealthy scalp.

Eligibility last updated 4/11/22. Questions regarding updates should be directed to the study team contact.

Eligibility last updated 9/23/22. Questions regarding updates should be directed to the study team contact.

• Children diagnosed with autism spectrum disorder (ASD).
• Between 2 years, 0 months to 4 years, 11 months of age.
• With less than phrased speech.
• Child must have at least one caregiver willing to participate in the study.

• Children and parents if they do not meet the above inclusion criteria.

   

Note: Placement of a central venous access catheter(s) (e.g., port or similar) is not
considered a major surgical procedure.

5. Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy.

6. Pregnant or nursing women.

Note: Women of child-bearing potential and men must agree- to use adequate contraception (hormonal or barrier method of birth control; or abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.

7. Participation in a clinical study involving administration of an investigational compound within the past 30 days prior to study entry.

8. Unwillingness or inability to comply with procedures required in this protocol.

9. Known allergy or hypersensitivity to the study drug(s) or one of the ingredients in the formulation (e.g., Trehalose dihydrate).

10. Existence of any surgical, medical or laboratory condition that, in the judgment of the clinical investigator, might interfere with the safety, distribution, metabolism
or excretion of the drug.

Eligibility last updated 4/11/22. Questions regarding updates should be directed to the study team contact.

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

Eligibility last updated 3/8/23 to match clinicaltrials.gov. Questions regarding updates should be directed to the study team contact.

• Clinical or mutational diagnosis of TSC consistent with (Northrup and Krueger, 2013):
  • Molecular confirmation of a pathogenic mutation in TSC1 or TSC2. A pathogenic mutation is defined as a mutation that clearly prevents protein synthesis and/or inactivates the function of the TSC1 or TSC2 proteins (e.g., nonsense mutation or frameshift mutations, large genomic deletions) or is a missense mutation whose effect on protein function has been established by functional assessment. The PI or designee must review the results of the genetic analysis and confirm that the causal relationship to the epilepsy syndrome is likely; OR
  • Clinical diagnosis of definite TSC which includes 2 major features or 1 major feature with ≥ 2 minor features.
• Major features:
  • Hypomelanotic macules (≥ 3, at least 5-mm diameter);
  • Angiofibroma (≥ 3) or fibrous cephalic plaque;
  • Ungual fibromas (≥ 2);
  • Shagreen patch;
  • Multiple retinal hamartomas;
  • Cortical dysplasiasa;
  • Subependymal nodules;
  • Subependymal giant cell astrocytomas;
  • Cardiac rhabdomyoma;
  • Lymphangioleiomyomatosis (LAM)**;
  • Angiomyolipomas (≥ 2)**.
• Minor features:
  • “Confetti” skin lesions;
  • Dental enamel pits (≥ 3;
  • Intraoral fibromas (≥ 2) Retinal achromic patch Multiple renal cysts Nonrenal hamartomas.

*   Includes tubers and cerebral white matter radial migration lines.
** A combination of the 2 major clinical features (LAM and angiomyolipomas) without other features does not meet criteria for a definite diagnosis.

• The investigator must document which of the features (major or minor) fulfill the clinical diagnostic criteria. 2. Male or female participants aged 1 through 65 years, inclusive. 3. Participant/parent or LAR willing to give written informed consent/assent, after being properly informed of the nature and risks of the study and prior to engaging in any studyrelated procedures. 4. Assent for participants over 7 years of age should be obtained if appropriate. 5. Failure to control seizures despite appropriate trial of 2 or more AEDs at therapeutic doses and for adequate duration of treatment per PI judgment. 6. Participants should be on a stable regimen of AEDs (including moderate or strong inducer or inhibitor anti-seizure medications eg, carbamazepine, phenytoin, etc.) at therapeutic doses for ≥ 28 days prior to the screening visit, and without a foreseeable change in dosing for the duration of the study. (Note: Minor dose adjustment to address tolerability and safety events may be allowed on case-by-case basis and it should be discussed with the study medical monitor.) 7. A history of at least 8 countable seizures per month in the 2 months prior to screening with no more than 1 seizure free week in each month. 8. Have an average of at least 2 primary endpoint seizures per week in the 28 days following the screening visit. The primary endpoint seizure types are defined as the following:
  • Focal motor seizures without impairment of consciousness or awareness;
  • Focal seizures with impairment of consciousness or awareness with motor features;
  • Focal seizures evolving to bilateral, tonic-clonic seizures.
• Generalized motor seizures including tonic-clonic, bilateral tonic, bilateral clonic, or atonic/drop seizures. Seizures that do not count towards the primary endpoint include:
  • Focal aware seizures without motor features;
  • Focal and generalized nonmotor seizures (e.g., absence or focal nonmotor seizures with or without impairment of awareness);
  • Infantile or epileptic spasms;
  • Myoclonic seizures.
• Participants with surgically implanted VNS will be allowed to enter the study provided that all of the following conditions are met:
  • The VNS has been in place for ≥ 1 year prior to the screening visit;
  • The settings must have remained constant for 3 months prior to the screening visit and are expected to remain constant throughout the study;
  • The battery is expected to last for the duration of the study.
• Parent/caregiver or the participant, as appropriate, is able and willing to maintain an accurate and complete daily seizure eDiary for the duration of the study.
• Able and willing to take IP (suspension) as directed with food TID.
•  Sexually active WOCBP must be using a medically acceptable method of birth control and have a negative quantitative serum β-HCG test collected at the initial screening visit. Childbearing potential is defined as a female who is biologically capable of becoming pregnant. A medically acceptable method of birth control includes intrauterine devices in place for 1 month prior to the screening visit, surgical sterilization, or adequate double barrier methods (e.g., diaphragm or condom and foam). An oral contraceptive alone is not considered adequate for the purpose of this study. Use of oral contraceptives in combination with another method (e.g., a spermicidal cream) is acceptable. In participants who are not sexually active, abstinence is an acceptable method of birth control.
• Male participants must agree to take all necessary measures to avoid causing pregnancy in their sexual partners during the study and for 30 days after the last dose of IP. Medically acceptable contraceptives include surgical sterilization (such as a vasectomy) and a condom used with a spermicidal gel or foam.
  • Note: The Epilepsy Study Consortium will review and classify all seizure types reported by the investigator, incorporating the medical history, genetic testing, seizure description, and historical records (including EEG, when available). This review and classification does not need to be completed prior to study entry but should be completed in parallel, and may complete after the participant has been enrolled in the study

• Previous exposure to GNX.
• Pregnant or breastfeeding.
• Participants who have been taking felbamate for less than 1 year prior to screening.
• Participants taking CBD preparations other than Epidiolex.
• A positive result on plasma drug screen for CBD or THC at Visit 1 (screening), with the exception of results that are fully explained by Epidiolex, which is being prescribed and managed by the investigator.
• Concurrent use of ACTH, prednisone or other glucocorticoid is not permitted, nor use of the strong inducers of CYP3A4, rifampin and St John’s Wort. Participants on ACTH, prednisone, or other systemically (non-inhaled or topical) administered steroids should be off the product > 28 days prior to screening. Rifampin and St John’s Wort must be discontinued at least 28 days before Visit 2, study drug initiation.
  • Note:  Use of concomitant intranasal or PRN topical steroids for dermatologic reactions and allergic rhinitis are allowed during the study;
  • This exclusion criterion does not prohibit the use of approved AEDs.
• Changes in any chronic medications within the 4 weeks prior to the screening visit. All chronic concomitant medications must be relatively stable in dose for at least 4 weeks prior to the screening visit unless otherwise noted. Small dose adjustment to manage tolerability and safety events is permitted and should be discussed with the study medical monitor.
• Participants who have epilepsy surgery planned during the study or who have undergone surgery for epilepsy within the 6 months prior to screening.
• An active CNS infection, demyelinating disease, degenerative neurological disease, or CNS disease deemed progressive as evaluated by brain imaging (MRI). This includes tumor growth which in the opinion of the investigator could affect primary endpoint seizure control.
• Any disease or condition (medical or surgical; other than TSC) at the screening visit that might compromise the hematologic, cardiovascular (including any cardiac conduction defect), pulmonary, renal, gastrointestinal, or hepatic systems; or other conditions that might interfere with the absorption, distribution, metabolism, or excretion of the IP, or would place the participant at increased risk or interfere with the assessment of safety/efficacy. This may include any illness in the past 4 weeks which in the opinion of the investigator may affect seizure frequency.
• Hepatic impairment sufficient to affect patient safety, or an AST/SGOT or ALT/SGPT > 3 × the ULN at screening or baseline visits and confirmed by a repeat test.
• Biliary impairment sufficient to affect patient safety, or total bilirubin levels > 1.5 × ULN at screening or baseline visit and confirmed by a repeat test. In cases of Gilbert’s Syndrome, resulting in stable levels of total bilirubin greater than ULN, the medical monitor can determine if a protocol exception can be made.
• Renal impairment sufficient to affect patient safety, or 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 (Levey et al, 2006). Cases of temporary renal insufficiency should be discussed with the medical monitor to determine the participant’s study continuation.
• Exposed to any other investigational drug or investigational device within 30 days or fewer than 5 half-lives prior to the screening visit. For therapies in which half-life cannot be readily established, the Sponsor’s Medical Monitor should be consulted.
• Unwillingness to avoid excessive alcohol use throughout the study.
• Have active suicidal plan/intent, active suicidal thoughts or a suicide attempt in the past 6 months.
• Known sensitivity or allergy to any component in the IP(s), progesterone, or other related steroid compounds.

Inclusion Criteria:

• Age (years) ≥ 18.
• Able to provide Written Informed consent.
• Systemic sclerosis as defined by VEDOSS or ACR/EULAR 2013 Classification criteria.

• Individuals < 18 years.
• History of IBD (Crohn’s disease or ulcerative colitis), microscopic colitis, or celiac disease.
• Pregnancy.
• Prior abdominal surgery (except hernia, fundoplication, C-section, hysterectomy, appendectomy, and cholecystectomy).
• Prior antibiotic use or new probiotic use in the last 2 weeks.

• Subject must be ≥ 18 years of age.
• Subject meets indications for TAVR using approved devices.
• The study patient has been informed of the nature of the study, agrees to its provisions, and has provided written informed consent as approved by the Institutional Review Board (IRB) of the respective clinical site.
• Subject is willing to comply with specified follow-up evaluations.
• Subject meets the legal minimum age to provide Informed Consent based on local regulatory requirements.

• Patient with any implanted or have an indication for treatment with rhythm management device (i.e., pacemaker, Cardiac Resynchronization Therapy (CRT) or Cardiac Resynchronization Therapy with cardioverter-defibrillator (CRT-D) at baseline.
• Any contraindication to the TAVR procedure according to the instructions for use.
• Subject is less than the legal age of consent, legally incompetent, or otherwise vulnerable.
• Patients who have a planned treatment with any other investigational device, drug or procedure (excluding registries) during the study period.

Eligibility last updated 6/24/22.   Questions regarding updates should be directed to the study team contact.

Eligibility last updated [date of initial abstraction or last Mod]. Questions regarding updates should be directed to the study team contact.

• An adult male patient who:
  • Is deemed eligible (or potentially/likely eligible) for PSMA-targeted radionuclide therapy by a Nuclear Medicine Physician or Radiologist in the Nuclear Medicine therapy practice, or by the Prostate Theranostic Tumor Board (PTuB).
  • Is acceptable to be potentially eligible for therapy but have a relative contraindication, such as a minor laboratory abnormality, and be on the list for discussion at the PTuB in the future.
  • Is acceptable to be eligible for PSMA-targeted radionuclide therapy in all regards except for having completed a PSMA-targeted PET scan showing PSMA-positive prostate cancer.
  • Is eligible to be documented in the medical record by the clinical practice.
  • Has not received a 68Ga-PSMA-11 PET/CT or PET/MR, or for whom a repeat 68Ga-PSMA-11 PET/CT exam is needed per the clinical practice to ensure eligibility.
  • Does not otherwise have access to a reimbursable clinical 68Ga-PSMA-11 PET scan.
  • An adult above the age of 18.

• A patient who is:
  • Under the age of 18.
  • Unable to consent per Mayo guidelines.
  • Unable to lay still, or otherwise successfully complete the imaging exam.

Eligibility last updated 4/15/22. 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.

• 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.

• Age 2-80 years at time of screening.
• Has a clinical diagnosis of type 1 diabetes:
  • 14–80 years of age: A clinical diagnosis of type 1 diabetes for 2 years or more as determined via medical record or source documentation by an individual qualified to make a medical diagnosis;
  • 7–13 years of age: A clinical diagnosis of type 1 diabetes for 1 year or more as determined via medical record or source documentation by an individual qualified to make a medical diagnosis;
  • 2-6 years of age: A clinical diagnosis of type 1 diabetes for 6 months or more, as determined via medical record/ source documentation by an individual qualified to make a medical diagnosis.
• Does not require a legally authorized representative to consent on their behalf due to mental or intellectual disability.
• Subject or parent/caregiver is literate and able to read the language offered in the pump or pump materials.
• Subject and/or legally authorized representative is willing to provide informed consent for participation.
• Is willing to perform fingerstick blood glucose measurements as needed.
• Is willing to wear the system continuously throughout the study.
• Must have a minimum daily insulin requirement (Total Daily Dose) of greater than or equal to 8 units.
• Has a Glycosylated hemoglobin (HbA1c) less than 10% (as processed by Central Lab) at time of screening visit.
  • Note: All HbA1c blood specimens will be sent to and tested by a National Glycohemoglobin Standardization Program (NGSP) certified Central Laboratory. HbA1c testing must follow NGSP standards.
• Has thyroid-stimulating hormone (TSH) in the normal range OR if the TSH is out of normal reference range, the Free T3 is below or within the lab’s reference range and Free T4 is within the normal reference range.
• Uses pump therapy prior to screening:
  • 7-80 years of age: greater than 6 months prior to screening (with or without CGM experience);
  • 2-6 years of age: greater than 3 months prior to screening (with or without CGM experience).
• Is willing to upload data from the study pump, must have Internet access, and a computer system, or compatible smartphone that meets the requirements for uploading the study pump.
• Is willing to take one of the following insulins and can financially support the use of either of the 2 insulin preparations as required during the run-in period: a. Humalog (insulin lispro injection) b. NovoLog (insulin aspart injection).
• Is willing to take Lyumjev insulin during the study period (supplied via Sponsor).

• Has hypersensitivity to insulin lispro or one of the excipients in Lyumjev®.
• Has a history of 2 or more episodes of severe hypoglycemia, which resulted in any the following during the 6 months prior to screening:
  • Medical assistance (i.e., Paramedics, Emergency Room [ER] or Hospitalization);
  • Coma;
  • Seizures. Has been hospitalized or has visited the ER in the 6 months prior to screening resulting in a primary diagnosis of uncontrolled diabetes.
• Has had DKA in the last 6 months prior to screening visit.
• Will not tolerate tape adhesive in the area of sensor placement as assessed by a qualified individual.
• Has any unresolved adverse skin condition in the area of sensor placement (e.g., psoriasis, dermatitis herpetiformis, rash, Staphylococcus infection).
• Is female of child-bearing potential and result of pregnancy test is positive at screening.
• Is sexually active female of child-bearing potential and is not using a form of contraception deemed reliable by the investigator.
• Is female and plans to become pregnant during the course of the study.
• Is being treated for hyperthyroidism at time of screening.
• Has diagnosis of adrenal insufficiency.
• Has taken any oral, injectable, or intravenous (IV) glucocorticoids within 8 weeks from time of screening visit, or plans to take any oral, injectable, or IV glucocorticoid during the course of the study.
• Is using hydroxyurea at time of screening or plans to use it during the study.
• Is actively participating in an investigational study (drug or device) wherein he/she has received treatment from an investigational study drug or investigational study device in the last 2 weeks.
• Is currently abusing illicit drugs.
• Is currently abusing marijuana.
• Is currently abusing prescription drugs.
• Is currently abusing alcohol.
• Using pramlintide (Symlin), DPP-4 inhibitor, liraglutide (Victoza or other GLP-1 agonists), metformin, canagliflozin (Invokana or other SGLT2 inhibitors) at time of screening.
• Has a history of visual impairment which would not allow subject to participate in the study and perform all study procedures safely, as determined by the investigator.
• Has elective surgery planned that requires general anesthesia during the course of the study.
• Has sickle cell disease, hemoglobinopathy; or has received red blood cell transfusion or erythropoietin within 3 months prior to time of screening.
• Plans to receive red blood cell transfusion or erythropoietin over the course of study participation.
• Is diagnosed with current eating disorder such as anorexia or bulimia.
• Has been diagnosed with chronic kidney disease that results in chronic anemia.
• Has a hematocrit that is below the normal reference range of lab used.
• Is on dialysis.
• Has serum creatinine of > 2 mg/dL.
• Has celiac disease that is not adequately treated as determined by the investigator.
• Has had any of the following cardiovascular events within 1 year of screening: myocardial infarction, unstable angina, coronary artery bypass surgery, coronary artery stenting, transient ischemic attack, cerebrovascular accident, angina, congestive heart failure, or ventricular rhythm disturbances.
• Has had history of cardiovascular event 1 year or more from the time of screening without:
  • a normal EKG and stress test within 6 months prior to screening or during screening; or
  • clearance from a qualified physician prior to receiving the study devices if there is an abnormal EKG or stress test.
• Has 3 or more cardiovascular risk factors listed below without a normal EKG within 6 months prior to screening or during screening or clearance from a qualified physician if there is an abnormal EKG:
  • Age > 35 years;
  • Type 1 diabetes of > 15 years’ duration;
  • Presence of any additional risk factor for coronary artery disease;
  • Presence of microvascular disease (proliferative retinopathy or nephropathy, including microalbuminuria);
  • Presence of peripheral vascular disease;
  • Presence of autonomic neuropathy.
• Is a member of the research staff involved with the study.

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

Eligibility last updated 1/13/23. Questions regarding updates should be directed to the study team contact.

• Patients referred to the Mayo Clinic cardio-oncology clinic.
• Adults ≥ 18 years old.

• Individuals < 18 years old.

Premenopausal group

• Age 40-48 at the time of original study recruitment.
• Regular menstrual periods for at least 1 year on no hormonal contraception at the time of their participation in the original study.

Postmenopausal group

• Age 52-60 at the time of original study recruitment.
• Confirmed menopausal status at the time of their participation in the original study: no menstrual periods for at least 1 year (but no more than 2 years).

• History of hysterectomy.
• History of surgical, chemical, or radiation-induced menopause (i.e., oophorectomy, aromatase inhibitors, chemotherapy for cancer treatment, or radiation therapy).
• Use of any drug that can affect estrogen production or signaling (e.g., GnRH agonists and antagonists, estrogen receptor modulators, etc.).
• Use of systemic estrogen and/or progesterone (oral contraceptives, contraceptive implants, hormone replacement therapy).
• Use of non-hormonal contraceptive methods that can affect the regularity of menstrual cycles (e.g., intrauterine devices).
• History of hypothalamic or pituitary disease (e.g., pituitary adenomas, empty sella, pituitary surgery, hypothalamic masses).
• Patients who denied future use of biological samples or further contact from the previous listed IRBs.

Eligibility last updated 4/18/22. Questions regarding updates should be directed to the study team contact.

• Female, 18 years of age or older.
• Women treated for breast cancer with radiation with a curative intent

• Non breast cancer.
• Children under 18-years of age.
• Non curative intent.

Eligibility last updated 4/19/22.  Questions regarding updates should be directed to the study team contact.

• Self-identify as Somali.
• Adult males and females who are older than 18 years of age.

• Anyone under 18 years or over 70 years.
• Positive pregnancy.

Eligibility last updated 3/8/23.  Questions regarding updates should be directed to the study team contact.

Inclusion Criteria: 

• ≥ 18 years of age.
• Subject must have a clinician-recorded diagnosis of  Pulmonary Hypertension (PH).
• Subject must have either PAH (WHO Group 1), PH due to left heart disease (WHO Group 2), PH due to lung disease (WHO Group 3), PH due to blood clots in the lungs (WHO Group 4), or PH with unclear and/or multifactorial mechanisms (WHO Group 5) based on a clinician-reported diagnosis.
• Subject is able to read and complete an English-language electronic survey.
• Subject has access to a computer or tablet to complete the electronic survey.
• Subject is willing and able to provide electronic informed consent.

• ≤ 18 years of age. 

Eligibility last updated 6/23/22. Questions regarding updates should be directed to the study team contact.

•  Patients must have a pre-identified:
  • Heterozygous genetic variant in the POMC gene or PCSK1 gene;
  • Heterozygous genetic variant in the LEPR gene;
  • Homozygous, heterozygous, or compound heterozygous variant in the SRC1;
  • Homozygous, heterozygous, or compound heterozygous variant in SH2B1 gene, or chromosomal 16p11.2 deletion encompassing the SH2B1 gene;
  • Heterozygous N221D variant in the PCSK1 gene; OR
  • Be an N221D variant of the PCSK1 gene If a patient has composite heterozygous variants eligible for the study she/he will be accounted for the higher category based on ACMG classification;
    • Example: If a patient is a composite heterozygous for POMC pathogenic variant, and LEPR VOUS, the patient will be categorized as POMC pathogenic.
  • If the 2 variants have the same ACMG classification, adjudication will be assigned to the less prevalent gene sub-study;
    • Example:
      • If a patient is a composite heterozygous for LEPR VOUS and SRC1 VOUS, the patient will be categorized as SRC1(sub-study 35c);
      • If a patient is a composite heterozygous for SH2B1 VOUS and SRC1 VOUS, the patient will be assigned to SRC1 (sub-study 35c).
  • If the investigator has genetics results on a patient who may be eligible for the study, but the genetics have not yet been categorized by a CLIA/CAP/ISO15189 certified laboratory, then Rhythm may provide testing and/or categorization through a third-party laboratory.
• Between 6 and 65 years of age at the time of provision of informed consent/assent.
• Obesity, defined as BMI ≥ 30 kg/m^2 for patients ≥ 18 years of age or BMI ≥ 95th percentile for age and gender for patients 6 up to 17 years of age, based on the United States (US) Centers for Disease Control and Prevention criteria.
• Patient and/or parent or guardian is able to communicate well with the Investigator, understand and comply with the requirements of the study (including once daily [QD] injection regimen and all other study procedures), and is able to understand and sign the written informed consent/assent. Patients who are unable to comply with all study procedures due to cognitive limitations or any other reason should not be enrolled into the study.
• Patient and/or parent or guardian reports that patient experienced childhood obesity, defined as the patient and/or parent or guardian reporting that the patient was significantly overweight during childhood.
• For women of child-bearing potential (WOCBP), agrees to use a highly effective form of contraception throughout the study and for 30 days following the study:
  •  Highly effective forms of contraception include:
    • Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, or transdermal);
    • Progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, or implantable)
    • Intrauterine device (IUD);
    • Sexual abstinence only if it is the preferred and usual lifestyle of the patient.
• Reported history of lifestyle intervention of diet and exercise.
• Reported history of hyperphagia.

• Recent intensive (within 2 months) diet and/or exercise regimen with or without the use of weight loss agents including herbal medications that has resulted in > 2% weight loss.
• Use of any medication that is approved to treat obesity within 3 months of first dose of study drug (e.g., orlistat, phentermine-topiramate, naltrexone-bupropion) if >2% weight loss in the last 3 months.
• History of Bariatric surgery with evidence of weight loss of > 2% in the last 3 months.
• Documented diagnosis of any psychiatric disorder(s) that the Investigator believes will interfere significantly with study compliance.
• Any suicidal ideation of type 4 or 5 on the Columbia Suicide Severity Rating Scale (CSSRS) during Screening, any suicide attempt in the past 5 years, or any suicidal behavior in the last month.
• Current, clinically significant pulmonary, cardiac or oncologic disease considered severe enough to interfere with the study and/or confound the results. Any patient with a potentially clinically significant disease should be reviewed with Rhythm to determine eligibility.
• HbA1C > 10% at Screening.
• History of significant liver disease other than non-alcoholic fatty liver disease (NAFLD) or nonalcoholic steatohepatitis (NASH).
• Glomerular filtration rate (GFR) < 30 mL/min at Screening.
• History or close family history (parents or siblings) of melanoma, or patient history of oculocutaneous albinism.
• Significant dermatologic findings relating to melanoma or pre-melanoma skin lesions (excluding non-invasive basal or squamous cell lesion), determined as part of a comprehensive skin evaluation performed by the Investigator during Screening. Any concerning lesions identified during Screening will be biopsied and results known to be benign prior to enrollment. If the pre-treatment biopsy results are of concern, the patient may need to be excluded from the study.
• Patient is, in the opinion of the Study Investigator, not suitable to participate in the study.
• Participation in any clinical study with an investigational drug/device within 3 months or 5 half-lives, whichever is longer, prior to the first day of dosing.
• Previously enrolled in a clinical study involving setmelanotide or any previous exposure to setmelanotide.
• Significant hypersensitivity to any excipient in the study drug.
• If female, pregnant or breastfeeding.

• Age 18 to 100 years old.
• Able to consent.

• Pregnant women, fetuses or neonaters.
• Prisoners.
• Children.
• Adults lacking capacity to consent.

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

• Dysfunctional right ventricular outflow tract (RVOT) conduit or previously implanted surgical valve.
• RVOT/PV (Pulmonic Valve) with ≥ moderate regurgitation and/or a mean RVOT/PV gradient of ≥ 35 mmHg.

• Inability to tolerate an anticoagulation/antiplatelet regimen.
• Active bacterial endocarditis or other active infections.

Eligibility last updated 5/13/22. Questions regarding updates should be directed to the study team contact.

• Group 1:
  • Age 18-80 years;
  • BMI ≥ 35 kg/m^2;
  • Eligible for bariatric surgery;
  • Ability to provide consent.
• Group 2:
  • Age 18-80 years;
  • BMI ≤ 30 kg/m^2;
  • Undergoing live donor nephrectomy;
  • Ability to provide consent.

• Pregnancy.
• Chronic Inflammatory Disease (e.g., rheumatoid arthritis).
• Active malignancy.
• Recent stroke or myocardial infarction.
• Solid organ transplant recipients.
• Therapeutic doses of immunosuppressive drugs (including calcineurin inhibitors and prednisone (> 10 mg/day).
• Senolytic supplements.
• Subjects on therapeutic doses of anticoagulants [including Warfarin (Coumadin), Rivaroxaban (Xarleto); Apixaban (Eliquis); Dabigatran (Pradaxa, Prazaxa)].
• Subjects deemed ineligible to comply with study protocol.

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