Leptin to Treat Lipodystrophy

Summary

This study will evaluate the safety and effectiveness of the leptin replacement therapy in treating lipoatrophy or lipodystrophy-a condition in which there is a total or partial loss of fat cells. Patients with lipodystrophy lack sufficient leptin, because this hormone is produced by fat cells. The leptin deficiency usually causes high blood lipid (fat) levels and insulin resistance that may lead to diabetes. Patients may have hormone imbalances, fertility problems, uncontrolled appetite, and liver disease due to fat accumulation.

Patients 15 years and older with lipodystrophy are eligible for this study. Candidates are screened with a medical history and physical examination, and fasting blood tests. Those enrolled undergo the following additional procedures:

* Ultrasound of the liver and, if abnormalities are found, possibly a liver biopsy
* Resting metabolic rate measurement - measures the amount of oxygen breathed at rest in order to calculate how many calories are required to maintain resting body functions
* Magnetic resonance imaging of the liver and other organs, and of muscle and fat
* Estimation of body fat - measurements of height, weight, hip size, and skin folds over the arms and abdomen to estimate body fat content
* Insulin tolerance test - measures blood glucose levels after administration of insulin. Insulin is given through an intravenous (IV) catheter (a thin tube placed in a vein) and blood is drawn 5 minutes before the test begins, when the test begins, and 5, 10, 15, 20 and 30 minutes into the test
* Oral glucose tolerance test - measures blood glucose and insulin levels after drinking a glucose (sugar) solution. Blood samples are drawn through an IV catheter 15 minutes before the test begins, at the time the test begins, and 30, 60, 90 and 180 minutes into the test
* Intravenous glucose tolerance test - measures tissue response to insulin and glucose after glucose is injected into a vein. The glucose injection is followed by a short infusion of insulin and then blood samples are taken over 3 hours to measure insulin and glucose levels
* Appetite level and food intake - measures hunger level and caloric intake. Patients are questioned about their hunger level, given a variety of foods they may choose to eat and questioned again at various intervals about hunger level. On another day, patients are given breakfast (usually a milkshake) and when they want to eat again, the appetite level and caloric intake study is repeated.
* Hormone function tests - the function of three hormones influenced by leptin (corticotropin-releasing hormone, thyrotropin-releasing hormone and luteinizing hormone-releasing hormone) are assessed. The hormones are injected intravenously and then blood samples are drawn.

When all the tests are completed, leptin therapy begins. The drug is injected under the skin twice a day for 4 months by the patient or a caregiver (similar to self-administered insulin injections for diabetes). Blood is drawn once a month to monitor the effects of treatment and drug side effects. At clinic visits scheduled 1, 2 and 4 months after therapy starts, patients have a physical examination and meet with a dietitian. Medication dosage is also increased at these visits. At the end of 4 months, all baseline studies described above are repeated. Throughout the study, all patients complete a form once a week, in which they record their symptoms. Patients with diabetes also measure their blood glucose levels at home before each meal and at bedtime.

Conditions

• Lipodystrophy

Interventions

DRUG

hu Leptin (A-100)

Sponsors & Collaborators

• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

  lead NIH

Study Design

Purpose

TREATMENT

Eligibility

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2000-06-30

Completion

2003-04-30

Countries

• United States

Study Locations