Congenital Hyperinsulinism is the most common cause of low blood sugar (hypoglycemia) in infants and children.Infants who are born with this problem have low blood sugar, which can cause seizures or brain damage.

We are doing this study to see if the patterns of abnormalities in controlling insulin in children and adults with hyperinsulinism are related to any underlying genetic cause and to identify possible new genetic causes.This will be done by standard clinical tests of insulin control: a glucose tolerance test, a protein tolerance test, and a fasting test.

The purpose of this study is to evaluate how safe and effective the drug Qsymia (Phentermine/Topiramate of Ph/T) is for children, adolescents, and young adults with hypothalamic obesity. We will also evaluate if Ph/T helps with weight loss and changes in hunger in patients with hypothalamic obesity.

If you are determined to be eligible, then your participation will last for approximately 8 months. Participants will be asked to complete up to 5 in-person visits and 5 telephone safety check-ins. During the study you will be randomly assigned to study drug (phentermine/topiramate) or placebo for 28 weeks.

You will complete study procedures including blood tests, ECGs, mobile cardiac outpatient telemetry, body composition scan, and questionnaires. Compensation and reimbursement of limited travel expenses is available.

Our team is working on a study to better understand neurological problems, including seizures and developmental delays, that occur in children with hyperinsulinism, including HI/HA syndrome, and type 1 diabetes mellitus. The study involves a one-day visit to The Children's Hospital of Philadelphia and The University of Pennsylvania for a specialized magnetic resonance imaging scan (MRI) of the brain, an electroencephalogram (EEG), blood draw, and completion of questionnaires to evaluate development and behavior. The entire study visit is expected to take about five hours. If you are interested in learning more, please contact us at HIResearch@email.chop.edu.

You or your child are being asked to take part in this research study because you have Glycogen Storage Disease Type III (GSD III). The purpose of this research study is to better understand blood sugar variability, muscle strength and function, and impact of Glycogen Storage Disease Type III (GSD III) on overall health. You will not receive any treatment for your GSD III as part of this study, but the information you provide will be helpful for the study sponsor, Ultragenyx Pharmaceutical Inc., to develop a new therapy for GSD III.

If you agree to take part, your participation will last for about 26 weeks and will involve up to 2 study visits to the hospital along with up to 26 phone calls. There will be no changes to your treatment regimen for GSD III as part of this study.

As a participant in the research you will:

• come to the hospital for 1-2 in person visits to complete interviews and questionnaires,
• wear a blinded continuous glucose monitor (CGM) 3 months and an unblinded CGM for 3 months,
• complete fingerstick blood sugar checks, maintain a nutrition diary for 3 or more weeks throughout the study,
• maintain a hypoglycemia symptom diary, and
• upload CGM and HHG device data to a study-provided laptop weekly.

The main risks of this study are from hypoglycemia related to your diagnosis of GSD III and a loss of confidentiality. There are no direct benefits to you for participating in this study but the information collected as part of this study will help researchers better understand GSD III.

Our team is working on a clinical drug trial that involves giving you a study drug that is not FDA-approved called RZ358. The goal of the trial is to test the study drug safety, how your body processes the drug, how the drug affects your body, and see if it can increase your blood sugar. If you agree to take part, your participation will last for up to 27 weeks and include 4 weeks of screening, 8 weeks of treatment, and a 15 week follow-up period. It is possible that treatment with the study drug infusions may improve your blood sugar levels and/or reduce the use of other medication(s) to prevent hypoglycemia. For more information, contact us at HIResearch@email.chop.edu.

The purpose of this study is to find out if an investigational drug called setmelanotide (RM-493) can help control body weight in people with certain genetic modifications in their genes that play a key role in the regulation of body weight. Males and females, age 6 to 65, with obesity and certain genetic variants (MC4R pathway) may be eligible to participate. If you are confirmed eligible for the study, then participation will last up to 64 Weeks. Participants will complete Screening (Up to 8 Weeks), Double-Blind Treatment (Up to 52 Weeks), and Follow-Up Period (4 Weeks). Participants will complete research procedures including physical exams, blood draws, ECGs, and questionnaires. Participant will also need to self-inject the study drug once daily for the duration of their participation.

This clinical trial is for patients with congenital hyperinsulinism (HI) who are experiencing low blood sugar on their current treatment. The purpose of this study is to find out if the study drug, named RZ358, helps improve blood sugar levels compared to current HI treatments. RZ358 is an experimental drug which the FDA has approved for use in this clinical trial, but it has not approved the study drug to be given outside of clinical research testing. The study drug is a specialized protein (called a monoclonal antibody) meant to decrease the effect insulin has on lowering blood sugar.

Participation will last for up to 33 weeks or up to 3 years overall for subjects who would like to join the open-label extension phase. This includes a 5-week Screening Period, a Treatment Period that lasts 24 weeks, and then either an 8-week Follow-up Period or a 2-year Extension Period where participants can continue to receive the study drug. Individuals do not need to participate in the 2-year extension part of the study to take part in the treatment and monitoring period. During the treatment period, participants will be given the study drug or a placebo. A placebo is an inactive substance used to compare how well the study drug works. Only study drug and not placebo is given during the extension period.

Participants in this trial will:

• Receive the study drug or a placebo 7 times during the treatment period
• Receive the study drug for up to 2 years in the optional extension period
• Have electrocardiograms (ECGs)
• Have ultrasounds of their liver
• Wear a continuous glucose monitor (CGM) and take fingerstick glucose checks
• Have research blood tests
• Complete study diaries and surveys

The main risks of this study are from the study drug. These include infusion reactions (redness, tenderness, irritation at the infusion site), headaches, dizziness, hypoglycemia (low blood sugar), upper respiratory infections (colds), and excess body hair growth. Participants may benefit if the study drug proves to be more effective than current HI medications.

We are currently enrolling adolescents ages 15-21 of South Asian ancestry, African American ancestry, and European American or "White" ancestry. This study is looking to better understand ancestry related differences in risks for developing cardiovascular disease and type 2 diabetes. The study involves 2 visits to the CHOP Main Hospital in Philadelphia, and participants will be compensated for their efforts.

Insulin therapy, commonly given as multiple daily injection therapy, is the only recommended treatment for Cystic Fibrosis Related Diabetes (CFRD). Traditional therapy for CFRD requires an intense daily effort related to diabetes care on top of the already burdensome management of Cystic Fibrosis. In this study, we will assess the safety and effectiveness of the iLet Bionic Pancreas, an automated insulin delivery system, which uses a continuous glucose monitor (CGM), an insulin pump, and a control formula that activates insulin delivery based on CGM glucose data.