This study will evaluate the safety and effectiveness of leptin replacement therapy in
patients with lipodystrophy (also called lipoatrophy). Patients have a total or partial loss
of fat cells. They also lack the hormone leptin, which 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, large appetite, and
liver disease due to fat accumulation.
Patients age greater than or equal to 6 months with significant lipodystrophy may be eligible
for this study. Participants will be admitted to the NIH Clinical Center for 10 days for the
following studies before beginning 12 months of leptin therapy:
- Insulin tolerance test
- Ultrasound of the liver and, if abnormalities are found, possibly liver biopsies.
- Fasting blood tests
- Resting metabolic rate
- Magnetic resonance imaging of the liver and other organs, and of muscle and fat.
- Pelvic ultrasound in women to detect ovarian cysts.
- Estimation of body fat
- Oral glucose tolerance test
- Intravenous glucose tolerance test
- Appetite level and food intake
- Hormone function tests
- Questionnaires to assess activity and mood
- 24-hour urine collections
Additional studies may include blood tests for genetic studies of lipodystrophy, a muscle
biopsy to study muscle proteins involved in regulating energy expenditure before and after
leptin replacement, and examination of a surgical specimen (if available) to study molecules
that may be involved in energy storage and use.
When the above tests are completed, leptin therapy begins. The drug is injected under the
skin twice a day for 4 months and then once a day, if feasible. The dose is increased at the
1- and 2-month visits. Follow-up visits at 1, 2, 4, 6, 8 and 12 months after therapy starts
include a physical examination, blood tests and a meeting with a dietitian. At the end of 12
months, all baseline studies described above are repeated. Patients record their symptoms
weekly throughout the study. Those with diabetes measure their blood glucose levels daily
before each meal and at bedtime.
Phase:
Phase 2
Details
Lead Sponsor:
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)