Therapeutic Approaches to HAART-Induced Lipodystrophy

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2013 by University of Texas Southwestern Medical Center
Sponsor:
Collaborator:
Amylin Pharmaceuticals, LLC.
Information provided by (Responsible Party):
Abhimanyu Garg, University of Texas Southwestern Medical Center
ClinicalTrials.gov Identifier:
NCT00461552
First received: April 16, 2007
Last updated: June 19, 2013
Last verified: June 2013
  Purpose

To determine the efficacy and safety of 4 therapeutic interventions on HAART-Induced lipodystrophy. The interventions are: 1) Dietary - the effect of a high carbohydrate vs.a high cis-monounsaturated fatty acid diet. 2) The effect of aerobic exercise with dietary advice. 3) The effect of Omega-3 Fish Oil Capsules. 4) The effect of leptin therapy. These interventions are aimed at improving the metabolic complications of HAART therapy such as elevated lipids, and insulin resistance or diabetes.


Condition Intervention Phase
HIV Infections
Lipodystrophy
Drug: Metreleptin (Leptin)
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: Therapeutic Approaches to HAART-Induced Lipodystrophy

Resource links provided by NLM:


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

Primary Outcome Measures:
  • fasting serum triglycerides [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • HDL cholesterol [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • LDL cholesterol [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • fasting serum glucose [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • fasting serum insulin [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • overall and regional adiposity [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 130
Study Start Date: January 2003
Estimated Study Completion Date: September 2016
Estimated Primary Completion Date: January 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Leptin ( still recruiting)
Leptin weight and gender based dose, sub-cutaneous, twice daily. Leptin versus placebo for entire 6 months double-blind.
Drug: Metreleptin (Leptin)
weight based, sub-cutaneous injection, twice daily
Placebo Comparator: Leptin Placebo
Placebo for Leptin, sub-Q injection twice daily.
Drug: Metreleptin (Leptin)
weight based, sub-cutaneous injection, twice daily

Detailed Description:

Patients with HAART-induced lipodystrophy report loss of subcutaneous (sc) fat from the extremities and face and excess fat accumulation in the neck and truncal region. They also are predisposed to metabolic complications of insulin resistance, such as, dyslipidemia and diabetes mellitus. The pathogenesis of HAART-induced lipodystrophy is not fully understood although PIs have been strongly implicated as the cause. The metabolic complications pose an increased risk of atherosclerosis and acute pancreatitis whereas changes in body fat distribution cause physical discomfort and psychological distress. Management of these problems poses a therapeutic challenge. We propose potentially safe therapeutic lifestyle changes as well as novel therapies for management of HAART-induced lipodystrophy and its metabolic complications. The hypotheses to be tested and the aims are:

Hypothesis 1: A diet rich in cis-monounsaturated fatty acids improves HAART-induced glucose intolerance and dyslipidemia in HIV-infected patients.

Aim 1: To compare acceptability and effects of isocaloric diets rich in carbohydrates and cis-monounsaturated fats, each given for 6 wk, on glucose and lipid metabolism in patients with HAART-induced dyslipidemia in a randomized, cross-over study.

Hypothesis 2: A regimen of aerobic exercise improves insulin resistance, dyslipidemia and body fat distribution in HIV-infected patients with HAART-induced lipodystrophy.

Aim 2: To determine the effects of a supervised aerobic exercise regimen and dietary advice on glucose and lipid metabolism, and body fat distribution in HIV-infected patients with HAART-induced lipodystrophy.

Hypothesis 3: The n-3 polyunsaturated fats improve HAART-induced dyslipidemia in HIV-infected patients.

Aim 3: To determine the lipid-lowering effects of n-3 polyunsaturated fats in a randomized, double-blind, placebo-controlled, crossover trial in HIV-infected patients with HAART-induced dyslipidemia.

Hypothesis 4: Leptin replacement improves insulin resistance, dyslipidemia and body fat distribution in patients with HAART-induced lipodystrophy and hypoleptinemia.

Aim 4 To study efficacy and safety of recombinant methionyl leptin (r-metHuleptin) in improving insulin sensitivity, dyslipidemia and body fat distribution in patients with HAART-induced lipodystrophy and hypoleptinemia using a randomized, double-blind, placebo-controlled, parallel design.

Results from these studies may help in designing therapeutic approaches to HAART-induced lipodystrophy and its metabolic complications as well as for prevention of these problems in HIV-infected patients being placed on HAART.

  Eligibility

Ages Eligible for Study:   14 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria - General inclusion:

  • Age > 14 years
  • HIV infection being treated with HIV-1 protease inhibitors for >6 months currently, or previous protease inhibitor therapy of at least 2 years duration with development of lipodystrophy and current stable therapy preferably for past 4 months.
  • Fasting serum triglycerides > 200 mg/dL

Exclusion Criteria - General exclusion:

  • Acute, ongoing AIDS-defining opportunistic infections.
  • Blood CD4 positive lymphocyte count < 200/mm3
  • Known liver disease due to causes other than nonalcoholic steatohepatitis with elevation of liver transaminases by more than two and a half times above the upper limits of normal (SGOT>105 U/L, SGPT>120 U/L) or total bilirubin (>1.5 mg/dL).
  • Hematocrit of less than 30%.
  • Current alcohol abuse (>7 drinks or 210 g per wk for women and >14 drinks or 420 g per wk for men).
  • Current substance abuse.
  • Uncontrolled diabetes mellitus with fasting plasma glucose > 180 mg/dL or hemoglobin A1c > 9%.
  • History of weight loss during the last 3 months.
  • Use of anorexiogenic drugs, thiazolidinediones, anabolic steroids and human growth hormone.
  • Major Neuro-psychiatric illnesses impeding competence or compliance.
  • Pregnant and lactating women.
  • Cancer excluding skin cancer other than melanoma.
  • Acute medical illnesses precluding participation in the studies.
  • Chronic renal insufficiency with serum creatinine > 2 mg/dL.
  • Untreated thyroid disorders such as hypothyroidism and hyperthyroidism. Each of the 4 treatment arms has additional specific inclusion and exclusion criteria
  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: NCT00461552

Contacts
Contact: Claudia Quittner, RN, BSN, MS 214-648-9296 claudia.quittner@utsouthwestern.edu
Contact: Zahid Ahmad, M.D. 214-648-2377 zahid.ahmad@utsouthwestern.edu

Locations
United States, Texas
UT Southwestern Medical Center Recruiting
Dallas, Texas, United States, 75390
Sub-Investigator: Vinaya Simha, M.D.         
Sub-Investigator: Zahid Ahmad, M.D.         
Sponsors and Collaborators
University of Texas Southwestern Medical Center
Amylin Pharmaceuticals, LLC.
Investigators
Principal Investigator: Abhimanyu Garg, M.D. Univeristy of Texas Southwestern Medical Center
  More Information

Additional 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: NCT00461552     History of Changes
Other Study ID Numbers: 063656
Study First Received: April 16, 2007
Last Updated: June 19, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Texas Southwestern Medical Center:
Lipodystrophy
HIV
HAART
HIV Lipodystrophy Syndrome
Lipodystrophy syndrome
HIV-Associated Lipodystrophy
HIV-Associated Lipodystrophy Syndrome
Treatment Experienced

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Lipodystrophy
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Skin Diseases, Metabolic
Skin Diseases
Lipid Metabolism Disorders
Metabolic Diseases

ClinicalTrials.gov processed this record on July 23, 2014