Clinical trial NCT00461552: Therapeutic Approaches to HAART-Induced Lipodystrophy
Official title: Therapeutic Approaches to HAART-Induced Lipodystrophy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: HIV Infections
Lipodystrophy
Keywords: Lipodystrophy
HIV
HAART
HIV Lipodystrophy Syndrome
Lipodystrophy syndrome
HIV-Associated Lipodystrophy
HIV-Associated Lipodystrophy Syndrome
Treatment Experienced
Lead sponsor: University of Texas Southwestern Medical Center
Sponsor class: OTHER
Collaborators: name: Amylin Pharmaceuticals, LLC.
First posted: 2007-04-18
Enrollment: 23
Sex: ALL
Minimum age (years): 14
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

We are only reporting the results of Aim 4 - (Leptin Study) here.

Eligibility 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

Primary outcomes:
measure: Fasting Serum Triglycerides
timeFrame: 6 months
Secondary outcomes:
measure: Body Weight (kg)
timeFrame: 6 months
Other outcomes:
Locations:
city: Dallas
country: United States
facility: UT Southwestern Medical Center
state: Texas
Study officials:
affiliation: Univeristy of Texas Southwestern Medical Center
name: Abhimanyu Garg, M.D.
role: PRINCIPAL_INVESTIGATOR
References: