Phase 2 N=103 Treatment

Leptin to Treat Lipodystrophy

Lipodystrophy

Bottom Line

View on ClinicalTrials.gov: NCT00025883 ↗

Enrolled (actual)

103

Serious AEs

9.7%

Results posted

Aug 2016

Primary outcome: Primary: Percentage of Glycosylated Hemoglobin at Baseline, 6 Months, and 12 Months on Treatment With Metreleptin — 8.4; 8.1; 6.6; 7.2 percentage of glycated hemoglobin — p=<0.001

Study Design & Population

Study type: Interventional
Phase: Phase 2
Interventions: Metreleptin (Drug)
Age: Pediatric, Adult, Older Adult · 0+ yrs
Sex: All
Sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Primary completion: Feb 2015

Outcome Measures

Outcome	Result	p-value
PRIMARY Percentage of Glycosylated Hemoglobin at Baseline, 6 Months, and 12 Months on Treatment With Metreleptin	8.4; 8.1; 6.6; 7.2; 6.4; 7.3	<0.001 sig
PRIMARY Triglycerides at Baseline, 6 Months, and 12 Months on Treatment With Metreleptin	467; 483; 198; 339; 180; 326	0.05

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 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.

Eligibility Criteria

INCLUSION CRITERIA:

All ethnic groups.

Males and females.

Age greater than or equal to 6 months.
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 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
Fasting plasma glucose greater than or equal to 126 mg/dL, or
2 hour plasma glucose greater than or equal to 200 mg/dL following a 75 gram (1.75gm/kg) oral glucose load, or
Diabetic symptoms with a random plasma glucose greater than or equal to 200 mg/dl
Fasting insulin greater than 30 micro units/ml.
Fasting hypertriglyceridemia greater than 200 mg/dL or postprandially elevated triglycerides greater than 500 mg/dL when fasting is clinically not indicated (e.g. in infants)

-Persons with impaired decision-making capacity and who may be unable to provide informed consent may participate in this study per the discretion of the Principal Investigator.

EXCLUSION CRITERIA

Pregnant women, women in their reproductive years who do not use an effective method of birth control, and women currently nursing or lactating within 6 weeks of having completed nursing.

Exclusions for underlying diseases likely to increase side effects or hinder objective data collection:

Known infectious liver disease
Known HIV infection
Current alcohol or substance abuse
Psychiatric disorder impeding competence or compliance
Active tuberculosis
Use of anorexiogenic drugs
Other condition(s) which in the opinion of the clinical investigators would impede completion of the study
Subjects who have known hypersensitivity to E. Coli derived proteins.
Subjects with acquired lipodystrophy and a hematologic abnormality such as neutropenia and/or lymphadenopathy

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT00025883). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.