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.
Phase:
Phase 2
Details
Lead Sponsor:
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)