Clinical Trials

Background: - Partial lipodystrophy can cause high blood fat levels and resistance to insulin. This can lead to health problems including diabetes. Researchers have found that the drug metreleptin improves health in people with this disease. Objective: - To test the safety and effectiveness of metreleptin. Eligibility: - People age 6 months and older with partial lipodystrophy who - have received metreleptin through NIH studies and shown improvement AND - cannot get metreleptin other ways. Design: - Participants will come to NIH approximately every 6 months during year one, then every 1 2 years. Financial assistance may be available for travel within the U.S. - At visits, participants will get a supply of metreleptin to take home for daily injections, or it can be shipped to them inside the U.S. They will have: - plastic catheter placed in an arm vein. - blood tests, urine collection, and physical exam. - oral glucose tolerance test, drinking a sweet liquid. - ultrasound of the heart, liver, uterus, and ovaries. A gel and a probe are placed on the skin and pictures are taken of the organs. - echocardiogram, which takes pictures of the heart with sound waves. - Resting Metabolic Rate taken. A plastic hood is worn over the head while the oxygen they breathe is measured. - Participants will have up to 3 DEXA scan x-rays per year. - Participants may have: - annual bone x-rays. - liver biopsies every few years. A needle will be inserted into the liver to obtain a small piece. Participants will sign a separate consent for this. - Participants must be seen regularly by their local doctors and have blood tests at least every 3-6 months at home.

Background: - Generalized lipodystrophy can cause high blood fat levels and resistance to insulin. This can lead to health problems including diabetes. Researchers have found that the drug metreleptin improves health in people with this disease. Objective: - To test the safety and effectiveness of metreleptin. Eligibility: - People ages 6 months and older with generalized lipodystrophy who: - have received metreleptin through NIH studies AND - cannot get it through approved or compassionate use mechanisms in their home country. Design: - Participants will come to NIH approximately every 6 months during year one, then every 1 2 years. Financial assistance may be available for travel within the U.S. - At visits, participants will get a supply of metreleptin to take home for daily injections. They will have: - plastic catheter placed in an arm vein. - blood tests, urine collection, and physical exam. - oral glucose tolerance test, drinking a sweet liquid. - ultrasound of the heart, liver, uterus, and ovaries. A gel and a probe are placed on the skin and pictures are taken of the organs. - echocardiogram, which takes pictures of the heart with sound waves. - Resting Metabolic Rate taken. A plastic hood is worn over the head while the oxygen they breathe is measured. - Participants will have up to 3 DEXA scan x-rays per year. - Participants may have: - annual bone x-rays. - liver biopsies every few years. A needle will be inserted into the liver to obtain a small piece. Participants will sign a separate consent for this. - Participants must be seen regularly by their local doctors and have blood tests at least every 3 6 months at home.

Leptin is a hormone produced by the fat cells that researchers have shown to play a role in controlling appetite. Certain people with severe insulin resistance have little or no leptin. The purpose of this study is to investigate people whose leptin levels have been found to be lower than 85 percent of the general population. Researchers will determine whether insulin levels in these participants improve when they are treated with genetically engineered leptin. Study participants must be age 8 years or older and must have severe insulin resistance syndrome and leptin deficiency. During an initial 7-day visit to the Clinical Center, researchers will evaluate participants' metabolic parameters, such as insulin responsiveness, lipid levels, appetite, and hormone levels. After taking these tests, participants will self-inject doses of leptin once or twice a day and will be monitored for treatment outcomes as well as side effects via follow-up visits. These inpatient follow-up visits will involve both blood tests and imaging studies at the Clinical Center at 4, 8, and 12 months after the initial visit, and every 6 months thereafter.

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.