Trial of Leptin Replacement Therapy in Patients With Lipodystrophy - Full Text View

Purpose

Lipodystrophies represent a therapeutic challenge with regards to insulin resistance, hypertriglyceridemia and fatty liver which often is coupled with significant adipose tissue loss. The purpose of the study is to examine the safety and efficacy of Leptin on subjects with lipodystrophy.

Condition	Intervention	Phase
Hypoleptinemia Generalized Lipodystrophy Partial Lipodystrophy Insulin Resistance	Drug: Leptin Drug: Placebo	Phase 2 Phase 3


Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Crossover Assignment Masking: Double Blind (Subject, Caregiver, Investigator) Primary Purpose: Treatment
Official Title:	Double-Blind, Placebo-Controlled Trial of Leptin Replacement Therapy in Patients With Lipodystrophy

Resource links provided by NLM:

Genetics Home Reference related topics: Berardinelli-Seip congenital lipodystrophy Chanarin-Dorfman syndrome cholesteryl ester storage disease

MedlinePlus related topics: Diabetes Medicines

Genetic and Rare Diseases Information Center resources: Barraquer-Simons Syndrome Lipodystrophy Sphingolipidosis

U.S. FDA Resources

Further study details as provided by University of Texas Southwestern Medical Center:

Primary Outcome Measures:

Project Specific: to determine if r-metHuLeptin can be safely replaced in hypoleptinemic patients with generalized and partial lipodystrophies. [ Time Frame: 12 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Project Specific: to determine if r-metHuLeptin administration is effective in improving glucose and lipid abnormalities in hypoleptinemic patients with generalized and partial lipodystrophies. [ Time Frame: 12 months ] [ Designated as safety issue: No ]


Estimated Enrollment:	24
Study Start Date:	April 2006
Estimated Study Completion Date:	December 2013
Primary Completion Date:	July 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: 1 Leptin Active Comparator for 4 months, then for 8 months.	Drug: Leptin Leptin injected subcutaneously twice a day, to be administered at 100% of the estimated replacement dose during the first month, which is a dosage of 0.03mg/kg for female children, 0.04mg/kg for adult females, and0.02 mg/kg for all males, and then at 200% subsequently, or placebo. Other Names: Recombinant-methionyl Human Leptin. r-metHuLeptin
Placebo Comparator: 2 Sugar pill Placebo for 4 months, then active comparator for 8 months.	Drug: Placebo Sugar pill

Detailed Description:

The mechanism by which leptin improves glucose and lipid control is not clear. We will examine the possible mechanisms of leptin action by studying the effects of leptin administration on food intake, insulin resistance, insulin secretory response, hepatic and intramuscular triglyceride stores in a large sample of patients with lipodystrophy.

Hypothesis: Leptin replacement in patients with generalized and partial lipodystrophy and hypoleptinemia will be safe and efficacious in improving the metabolic abnormalities associated with insulin resistance.

Eligibility


Ages Eligible for Study:	6 Years to 70 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

age > 6 years
Partial and generalized lipodystrophy
Serum leptin levels less than the 7th percentile of normal values reported by the 3rd National Health and Nutrition Examination survey (less than 7.0 ng/mL in females and less than 3/0 ng/mL in males)
Presence of at least one of the following metabolic abnormalities:
1. Type 2 Diabetes Mellitus
2. Fasting serum insulin >20 uU/mL
3. Fasting serum triglycerides > 300 mg/dL
4. Previous participation in leptin trial (Amgen 991265, GCRC 660) - for Part B of the Study.

Exclusion Criteria:

Known liver disease due to causes other than non-alcoholic steatohepatitis.
Hematocrit of less than 30%.
Current alcohol or substance abuse.
Use of anorexigenic drugs, anabolic steroids, GH and thiazolidinediones
Active tuberculosis
Psychiatric disorder impeding competence or compliance
Malignancies
HIV infection
Subjects who have a known hypersensitivity to E. Coli derived proteins
Other condition, which in the opinion of the clinical investigators would impede completion of the study.

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00896298

Locations


United States, Texas
UT Southwestern Medical Center
Dallas, Texas, United States, 75390

Sponsors and Collaborators

University of Texas Southwestern Medical Center

Investigators


Principal Investigator:	Abhimanyu Garg, MD	UT Southwestern Medical Center

More Information

No publications provided


Responsible Party:	Abhimanyu Garg, Chairman, Division Nutrition and Metabolic Diseases, Professor Internal Medicine, University of Texas Southwestern Medical Center
ClinicalTrials.gov Identifier:	NCT00896298 History of Changes
Other Study ID Numbers:	0502-294
Study First Received:	May 8, 2009
Last Updated:	June 19, 2013
Health Authority:	United States: Food and Drug Administration

Keywords provided by University of Texas Southwestern Medical Center:


Lipodystrophy Insulin secretory response

Additional relevant MeSH terms:


Insulin Resistance Lipodystrophy Lipodystrophy, Congenital Generalized Genetic Diseases, Inborn Glucose Metabolism Disorders Hyperinsulinism	Lipid Metabolism Disorders Lipid Metabolism, Inborn Errors Metabolic Diseases Metabolism, Inborn Errors Skin Diseases Skin Diseases, Metabolic

ClinicalTrials.gov processed this record on February 27, 2015