Diet, Exercise &/or Rosiglitazone for HIV-Associated Insulin Resistance

Condition(s) targeted: HIV Infections; Insulin Resistance; Visceral Adiposity; Obesity

Intervention: Weight loss through diet and exercise (Behavioral); Rosiglitazone insulin sensitizing agent (Drug)

Phase: N/A

Status: Recruiting

Sponsored by: St. Luke's-Roosevelt Hospital Center

Official(s) and/or principal investigator(s):
Donald P Kotler, MD, Principal Investigator, Affiliation: St. Luke's-Roosevelt Hospital Center, Columbia University
Jeanine B Albu, MD, Principal Investigator, Affiliation: St. Luke's-Roosevelt Hospital Center, Columbia University

Overall contact:
T. Cris Pitea, MD, Phone: 212-523-3202, Email: TPitea@chpnet.org

The purpose of this study is to determine if, in men and women with excess abdominal fat and insulin resistance, people with HIV infection respond differently than people without HIV to interventions that typically improve body fat distribution and insulin resistance. The specific interventions are:

a. Diet+exercise program.

b. Rosiglitazone treatment.

c. A combination treatment of diet+exercise program and rosiglitazone.

Official title: Effect of Diet, Exercise and Rosiglitazone on Regional Fat and Insulin Resistance in HIV-Infected and Uninfected Men and Women

Study design: Interventional, Treatment, Randomized, Double-Blind, Placebo Control, Parallel Assignment, Safety/Efficacy Study

Primary outcome:

Insulin sensitivity

Body composition

Secondary outcome:

Quality of life

Strength and fitness

Lipid profile

Additional cardiovascular risk indicators

Detailed description: A constellation of nutritional alterations in HIV-infected patients receiving highly active antiretroviral therapies (HAART), including body fat redistribution with subcutaneous adipose tissue (SAT) wasting and visceral adipose tissue (VAT) accumulation, hyperlipidemia, and insulin resistance (IR) has been described. There is a major concern that these developments will be associated with adverse clinical outcomes related to atherosclerosis, as suggested by several case reports (Henry 1998, Behrens 1998, Gallet 1998, Vittecoq 1998). Although there are well documented associations among body fat distribution, insulin resistance, and adverse health outcomes, especially accelerated atherosclerosis, in non-HIV infected individuals, it is unclear if the relationships are affected by HIV infection, or if they reflect the same outcomes. This information is important, since understanding the interrelationships between body fat distribution and metabolism may guide the development of treatment strategies.

The specific hypotheses to be tested are:

1. HIV infection does not affect the relative reductions in visceral (VAT) and subcutaneous adipose tissue(SAT) resulting from diet + exercise, but decreases the effect of this therapy on insulin resistance.

2. HIV infection decreases the changes in insulin resistance and body composition (increase in SAT and decrease in VAT) expected with rosiglitazone.

3. The combination treatment of diet+exercise and rosiglitazone will reduce VAT to a greater extent than rosiglitazone alone, and will improve insulin resistance to greater extent than diet and exercise alone, however these effects will be blunted in HIV-infected subjects.

Minimum age: 20 Years. Maximum age: 60 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

- HIV-infected or uninfected.

- BMI at least 25.

- Excess visceral adipose tissue. Excess VAT will be determined in HIV+ and HIV- groups of men by a waist hip ratio > 0. 95 and a waist circumference >88. 2 cm, and in women by a waist: hip >0. 9 and waist circumference >75. 3 cm.

- Insulin resistance (fasting serum insulin level >16 μU/ml).

Exclusion Criteria:

- unable to tolerate MRI

- clinical evidence of active liver disease or a significantly abnormal liver function test (ALT >2. 5x the upper limit of normal).

- severe hyperlipidemia (fasting plasma triglycerides >500 mg/dL or fasting total cholesterol >300mg/dL)

- current coronary artery disease including angina

- peripheral vascular disease

- uncontrolled hypertension

- participation in a regular exercise program

T. Cris Pitea, MD, Phone: 212-523-3202, Email: TPitea@chpnet.org

St. Luke's-Roosevelt Hospital Center, New York, New York 10025, United States; Recruiting

Starting date: July 2005
Ending date: July 2007
Last updated: April 19, 2007