Clinical Trial: Leptin to Treat Lipodystrophy

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Long-Term Efficacy of Leptin Replacement in Treatment of Lipodystrophy

Brief Summary:

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 mus

Detailed Summary:

Lipoatrophic diabetes is a syndrome characterized by insulin resistance in association with a paucity of adipose tissue. Patients with severe lipoatrophy die prematurely, typically from the complications of diabetes or liver disease. Experiments with lipoatrophic mice suggest that the insulin resistance is caused by the lack of adipose tissue. Adipose tissue normally produces leptin, a hormone that increases insulin action. For the last fourteen years, we have been studying the extent to which leptin deficiency causes diabetes in lipoatrophic patients. In fact, in our initial study we have seen nearly 60% amelioration of fasting glucose, triglycerides and free fatty acid levels and about 2% actual decreases from baseline HbA1c levels with 4 months of leptin replacement therapy. This response has continued to be sustained, as we continue to follow patients that have now received leptin replacement therapy for fourteen years.

This is an open-labeled study. The study monitors the safety and efficacy of recombinant methionyl human leptin (A-100) replacement in children and adults. We are looking at the long-term effects of leptin replacement on extended therapy. In this long-term replacement protocol, we will monitor metabolic control (e.g. glucose, insulin, and triglyceride levels) as primary outcome measures. Ancillary studies will evaluate the effect of Metreleptin on other hormonal axes, growth and development and on liver pathology.

We continue to evaluate the efficacy in a broader leptin deficient population of patients with lipodystrophy. Current inclusion criteria in patients greater than or equal to 5 years include female patients with leptin levels < 12 ng/mL and male patients with leptin levels < 8 ng/mL. We continue to seek patients who meet these criteria. In children ages 6 months 5 years, we will use a cut
Sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Current Primary Outcome:

  • Percentage of Glycosylated Hemoglobin at Baseline, 6 Months, and 12 Months on Treatment With Metreleptin [ Time Frame: Baseline, 6 months, 12 months ]
    Percentage of glycosylated hemoglobin at Baseline, 6 months, and 12 months on treatment with metreleptin
  • Triglycerides at Baseline, 6 Months, and 12 Months on Treatment With Metreleptin [ Time Frame: Baseline, 6 months, 12 months ]


Original Primary Outcome:

Current Secondary Outcome:

Original Secondary Outcome:

Information By: National Institutes of Health Clinical Center (CC)

Dates:
Date Received: October 27, 2001
Date Started: October 2001
Date Completion:
Last Updated: August 12, 2016
Last Verified: August 2016