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Sponsored by: |
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) |
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Information provided by: | National Institutes of Health Clinical Center (CC) |
ClinicalTrials.gov Identifier: | NCT00025883 |
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.
Candidates will be screened with a physical examination and blood tests. Participants will be admitted to the NIH
Clinical Center for 10 days for the following studies before beginning 12 months of leptin therapy:
Condition | Intervention | Phase |
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Lipodystrophy |
Drug: Metreleptin |
Phase II |
Study Type: | Interventional |
Study Design: | Treatment |
Official Title: | Long-Term Efficacy of Leptin Replacement in Treatment of Lipodystrophy |
Estimated Enrollment: | 99999999 |
Study Start Date: | October 2001 |
Estimated Study Completion Date: | October 2003 |
Estimated Primary Completion Date: | October 2003 (Final data collection date for primary outcome measure) |
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 eight 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 eight 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-off leptin level of 6 ng/mL in both genders.
Patients who are greater than or equal to age 5 years will be evaluated every 4 months during the first year of therapy. If no improvements are seen after 4 months of therapy, then the study medication may be increased to 150% of the predicted dose (0.09mg/kg/day for males and girls less than 10 years of age/ 0.12mg/kg/day for females 10 years of age and older) from 4 months to 1 year on therapy. If no improvements are seen after increasing to 150% of the predicted dose, then the study medication will be withdrawn. If the patient shows improvements in his/her metabolic parameters while on leptin, the patient will be invited to continue taking the study medication. The investigators will strive for all patients responding to leptin to bring their metabolic parameters into the normal range. The maximum dose of leptin that will be given is 0.24 mg/kg/day for females 10 and older, and 0.12 mg/kg/day for males and females less than 10 years of age. After the first year of treatment, the patient will be evaluated every 6 months through the second year of treatment, and then the study period will end. After two years of treatment, extending the treatment period on an annual basis will be the decision of the patient, principal investigator and Amylin, Inc. Leptin is supplied by Amylin, Inc., and is currently only available through research studies. Neither the NIH nor Amylin, Inc. can guarantee that leptin will be available indefinitely and/or after the study ends.
All patient referrals for acceptance into the protocol, are initiated by the physician/health care provider.
Ages Eligible for Study: | 6 Months and older |
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | No |
All ethnic groups.
Males and females.
Circulating leptin levels less than 12.0 ng/ml in females and less than 8.0 ng/ml in males as measured by Linco assay on a specimen obtained after an overnight fast. In children ages 6 months - 5 years, a circulating leptin level of less than 6 ng/mL will be used. Leptin samples will be run through Millipore Laboratories, who use the Linco Assay, which has been the assay previously used to measure leptin levels throughout this study period.
Presence of at least one of the following metabolic abnormalities:
Presence of diabetes as defined by the 2007 ADA criteria
EXCLUSION CRITERIA:
Pregnant women, women in their reproductive years who do not use an effective method of birth control, currently nursing or lactating within 6 weeks of having completed nursing, and persons who are unable to provide informed consent will be excluded from the study.
Exclusions for underlying diseases likely to increase side effects or hinder objective data collection:
Contact: Patient Recruitment and Public Liaison Office | (800) 411-1222 | prpl@mail.cc.nih.gov |
Contact: TTY | 1-866-411-1010 |
United States, Maryland | |
National Institutes of Health Clinical Center, 9000 Rockville Pike | Recruiting |
Bethesda, Maryland, United States, 20892 |
Responsible Party: | National Institutes of Health ( Phillip Gorden, M.D./National Institute of Diabetes and Digestive and Kidney Diseases ) |
Study ID Numbers: | 020022, 02-DK-0022 |
Study First Received: | October 27, 2001 |
Last Updated: | August 24, 2009 |
ClinicalTrials.gov Identifier: | NCT00025883 History of Changes |
Health Authority: | United States: Federal Government |
Lipoatrophic Diabetes Leptin Diabetes Mellitus Hypertriglyceridemia NASH |
Lipodystrophy Leptin Lipoatrophic Diabetes Diabetes |
Metabolic Diseases Hypertriglyceridemia Skin Diseases Lipodystrophy, Congenital Generalized |
Lipodystrophy Diabetes Mellitus Metabolic Disorder Lipid Metabolism Disorders |
Metabolic Diseases Skin Diseases Skin Diseases, Metabolic Lipodystrophy Lipid Metabolism Disorders |