Lipodystrophy (LD) syndromes are a group of rare disorders that affect how a person s body
can store and use fat tissue. Many people with LDs become severely insulin resistant. Some
people are insulin resistant because of a variant in the insulin receptor gene. Insulin
resistance causes many health problems.
To learn if blocking the effects of growth hormone in the body will help people with severe
Adults aged 18 to 65 years with either a known variant in the insulin receptor gene or with a
diagnosis of partial LD.
Participants will have 2 hospital stays, about 1 month apart. Each stay will be 3 or 4
During each hospital stay, participants will have many tests. They will have a physical exam
with blood tests. They will have all of their urine collected for a 24-hour period. They will
have scans to measure their muscle, bone, and fat tissues. They will have tests to measure
metabolism and insulin sensitivity. They may have an optional biopsy of fat tissue.
During the first hospital visit, participants will learn how to give themselves shots of a
drug (pegvisomant) that blocks growth hormone. The drug is injected under the skin.
Participants will continue to give themselves these shots once a day at home.
After the first hospital visit, participants will talk on the phone with members of the study
team once each week. After 2 weeks they will have blood drawn for tests.
Participants will stop the shots after the second hospital visit.
Lipodystrophy is a health problem in which the body does not have enough fat tissue. People
with lipodystrophy may not make enough of the hormone leptin. Leptin regulates hunger. Low
leptin levels trigger hunger. People with lipodystrophy can have many health problems. They
may take a drug (metreleptin) that mimics leptin. Little is known about how taking
metreleptin may affect a pregnancy. Metreleptin may be helpful or harmful to pregnant women.
It may also affect the health of the child who is born.
This natural history study will collect data about the effects of taking metreleptin while
Women aged 18 years or older with lipodystrophy who have been pregnant. Women who did and who
did not take metreleptin during their pregnancies are needed. Children of women with
lipodystrophy who took this drug during pregnancy are also needed.
Participants will have 1 study visit. This visit may be by phone, by telehealth, or
Participants will answer questions about their pregnancies.
They will discuss any health problems they had.
They will be asked about any medicines they took before and during their pregnancies.
They will be asked about the health of their children.
Participants medical records will be reviewed.
Participants may need to provide a blood sample. They may also be asked to provide a sample
Participants children may also be asked to provide a blood sample....
Two cohorts are being studied based on leptin levels. Cohort A is composed of patients with
baseline leptin <8.0 ng/mL and Cohort B is composed of patients with baseline leptin 8.0 to
The primary objectives will be evaluated for patients in Cohort A only:
- To evaluate the effect of REGN4461 on fasting triglycerides (TG) in patients with
elevated baseline fasting TG
- To evaluate the effect of REGN4461 on hyperglycemia in patients with elevated baseline
Hemoglobin A1c (HbA1c)
The following secondary objectives of the study will be evaluated for Cohort B and for the
combined set of Cohorts A plus B:
- To evaluate the effect of REGN4461 on fasting TG levels in patients with
- To evaluate the effect of REGN4461 on glycemic control in patients with hyperglycemia
The following secondary objectives of the study will be evaluated for Cohorts A and B
separately, and for the combined set of Cohorts A plus B:
- To evaluate the effect of REGN4461 on liver fat in patients with hepatic steatosis
- To evaluate the effect of REGN4461 on hunger
- To evaluate safety and tolerability of REGN4461
- To characterize the concentration profile of REGN4461 over time
- To assess immunogenicity to REGN4461
The trial is Open with a status of Active, not recruiting.
NIDDK Site Investigator:
Rebecca J Brown, M.D.
Principal Investigator for all sites:
Clinical Trial Management, Regeneron Pharmaceuticals
Patients with mutations of the insulin receptor have diabetes that is challenging to control
with conventional therapies, leading to early morbidity and mortality. We hypothesize that
recombinant leptin (metreleptin) in these patients will improve glycemia control.
Primary Objective: To determine if 1 year of metreleptin will improve glycemia control in
patients with genetic defects of the insulin receptor. Secondary Objectives: To determine
mechanisms by which metreleptin improves glycemia.
Primary Endpoint: Hemoglobin A1c.
Secondary Endpoints: fasting plasma glucose, fasting insulin/C-peptide,
glucose/insulin/C-peptide area under the curve during oral glucose tolerance test.
20 male or female patients with mutations of the insulin receptor, age (Bullet)5 years, at
the NIH Clinical Center.
Description of Sites/Facilities Enrolling Participants: Description of Study Intervention:
NIH Clinical Center
Open label study of metreleptin, 0.2 mg/kg/day (max dose 0.24 mg/kg/day).
The trial is Open with a status of Active, not recruiting.
The study will allow researchers to obtain blood, plasma, DNA, and RNA for genetic studies of
insulin. There will be a focus on the causes of insulin resistance and diabetes mellitus.
Insulin is a hormone found in the body that controls the level of sugar in the blood. Insulin
resistance refers to conditions like diabetes when insulin does not work properly. In this
study researchers would like to compare patients with diabetes and other forms of insulin
resistance to normal individuals. The study will investigate how insulin attaches to cells.
Researchers will take 4 to 6 ounces (100-150 ml) of blood from adult patients and may request
up to 12 ounces (one unit) of blood if necessary. Skin samples may be taken for a biopsy if
further genetic testing is necessary. In addition some patients may be asked not to eat for
up to 72 hours prior to testing....