Trial of Leptin Replacement Therapy in Patients With Lipodystrophy

• ClinicalTrials.gov Identifier: NCT00896298
• Recruitment Status: Completed
• First Posted: May 11, 2009
• Results First Posted: March 5, 2019
• Last Update Posted: April 2, 2019
• Sponsor: University of Texas Southwestern Medical Center
• Information provided by (Responsible Party): Abhimanyu Garg, University of Texas Southwestern Medical Center

Tracking Information

• First Submitted Date: May 8, 2009
• First Posted Date: May 11, 2009
• Results First Submitted Date: January 15, 2019
• Results First Posted Date: March 5, 2019
• Last Update Posted Date: April 2, 2019
• Study Start Date: April 2006
• Actual Primary Completion Date: November 2014 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 28, 2019)

• Fasting Serum Triglycerides [ Time Frame: 4 months ]
• HbA1c [ Time Frame: 4 months ]

• Original Primary Outcome Measures (submitted: May 8, 2009): Project Specific: to determine if r-metHuLeptin can be safely replaced in hypoleptinemic patients with generalized and partial lipodystrophies. [ Time Frame: 12 months ]

Current Secondary Outcome Measures (submitted: February 28, 2019)

• Fasting Serum Glucose [ Time Frame: 4 months ]
• Body Weight [ Time Frame: 4 months ]

• Original Secondary Outcome Measures (submitted: May 8, 2009): 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 ]
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Trial of Leptin Replacement Therapy in Patients With Lipodystrophy
• Official Title: Double-Blind, Placebo-Controlled Trial of Leptin Replacement Therapy in Patients With Lipodystrophy
• Brief Summary: 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.

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.

• Study Type: Interventional
• Study Phase: Phase 2; Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Care Provider, Investigator); Primary Purpose: Treatment

Condition

• Hypoleptinemia
• Generalized Lipodystrophy
• Partial Lipodystrophy
• Insulin Resistance

Intervention

• 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
• Drug: Placebo
  Sugar pill

Study Arms

• Active Comparator: 1 Leptin
  Active Comparator for 4 months, then for 8 months.
  Intervention: Drug: Leptin
• Placebo Comparator: 2 Sugar pill
  Placebo for 4 months, then active comparator for 8 months.
  Intervention: Drug: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: February 28, 2019): 25
• Original Estimated Enrollment (submitted: May 8, 2009): 24
• Actual Study Completion Date: November 2014
• Actual Primary Completion Date: November 2014 (Final data collection date for primary outcome measure)

Eligibility 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 6 Years to 70 Years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT00896298
• Other Study ID Numbers: 0502-294
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Abhimanyu Garg, University of Texas Southwestern Medical Center
• Study Sponsor: University of Texas Southwestern Medical Center
• Collaborators: Not Provided

Investigators

• Principal Investigator: Abhimanyu Garg, MD; UT Southwestern Medical Center

• PRS Account: University of Texas Southwestern Medical Center
• Verification Date: March 2019