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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: | NCT00005905 |
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:
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.
Condition | Intervention | Phase |
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Lipodystrophy |
Drug: hu Leptin (A-100) |
Phase II |
Study Type: | Interventional |
Study Design: | Treatment, Safety/Efficacy Study |
Official Title: | Efficacy of Leptin Replacement in Treatment of Lipodystrophy |
Estimated Enrollment: | 20 |
Study Start Date: | June 2000 |
Estimated Study Completion Date: | April 2003 |
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. To what extent does leptin deficiency cause diabetes in lipoatrophic patients? In one mouse model of lipoatrophy, leptin administration reversed the diabetes and liver disease. In a different, more severely adipose-deficient mouse, the effects of leptin treatment were detectable, but more modest.
In this protocol, to be carried out at both the NIH and the University of Texas in Dallas, we test the hypotheses that leptin can be safely administered to patients with lipoatrophic diabetes and they will benefit from treatment with A-100 (recombinant form of human leptin provided by Amgen).
We will study patients with lipoatrophy, low leptin levels, and at least one of the following metabolic abnormalities: severe insulin resistance, diabetes, and/or hypertriglyceridemia.
We will treat patients with A-100 injections for four months, with inpatient studies at baseline, 1, 2, and 4 months of treatment. In the core protocol, we will monitor metabolic control (e.g. glucose, insulin, free fatty acid, and triglyceride levels). Ancillary studies will evaluate the effect of A-100 on the gonadal axis and on liver pathology.
After 8 months of treatment, we will offer a withdrawal study to the patient requiring an inpatient admission and controlled diet. Afterwards leptin therapy will resume in a long-term extension study with follow up visits every 6 months. Metabolic parameters will continue to be followed, along with body fat imaging studies, gonadotropin monitoring, and liver function analysis.
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | No |
INCLUSION CRITERIA:
All ethnic groups
Males and females
Age greater than 14 years
Clinically-significant lipodystrophy, identified by the study physician during the physical examination as an absence of fat outside the range of normal variation and/or identified as a disfiguring factor by the patient.
Circulating leptin levels less than 4.0 ng/ml in females and less than 3.0 ng/ml in males as measured by Linco assay on at least 2 occasions.
Presence of at least one of the following metabolic abnormalities:
Presence of diabetes as defined by the 1997 ADA criteria: a) fasting plasma glucose greater than or equal to 126 mg/dL, or b) 2 hour plasma glucose greater than or equal to 200 mg/dL following a 75 gram oral glucose load, or c) diabetic symptoms with a random plasma glucose greater than or equal to 200 mg/dL.
Fasting insulin greater than 30 micrograms/ml;
Fasting hypertriglyceridemia greater than 200 mg/dl.
EXCLUSION
General: Pregnant women, women in their reproductive years who do not use an effective method of birth control, women 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 disease likely to increase side effects or to hinder objective data collection:
Known liver disease due to causes other than non-alcoholic steatohepatitis
Current alcohol or substance abuse
Psychiatric disorder impeding competence or compliance
Active tuberculosis
Use of anorexiogenic drugs
Other condition which in the opinion of the clinical investigators would impede completion of the study
Subjects who have a known hypersensitivity to E. Coli derived proteins
Study ID Numbers: | 000146, 00-DK-0146 |
Study First Received: | June 9, 2000 |
Last Updated: | March 3, 2008 |
ClinicalTrials.gov Identifier: | NCT00005905 History of Changes |
Health Authority: | United States: Federal Government |
Adipocyte - Development Insulin Resistance Dyslipidemia |
Diabetes Mellitus Non-Alcoholic Steatohepatitis Leptin Replacement |
Metabolic Diseases Skin Diseases Lipodystrophy Diabetes Mellitus Insulin Resistance |
Metabolic Disorder Insulin Dyslipidemias Lipid Metabolism Disorders |
Metabolic Diseases Skin Diseases Skin Diseases, Metabolic Lipodystrophy Lipid Metabolism Disorders |