Metformin and Rosiglitazone, Alone or in Combination, in HIV-Infected Patients With Insulin and Fat Abnormalities
- Conditions
- HIV InfectionsLipodystrophyHyperinsulinemia
- Registration Number
- NCT00015691
- Brief Summary
The purpose of this study is to see whether metformin alone, rosiglitazone alone, or metformin and rosiglitazone together will lower insulin levels in the blood and decrease fat in the abdomen or other parts of the body.
Studies have shown that certain anti-HIV medications can cause a number of side effects, including high blood sugar (resulting from the body's failure to use insulin), high insulin, and excess fat build-up in the abdominal area. These side effects are known to increase the risk of heart disease. Metformin and rosiglitazone are 2 drugs that have been shown to lower insulin resistance and lessen abdominal fat in patients who are not HIV-infected. This study will investigate the use of these drugs in HIV-infected patients.
- Detailed Description
Recent studies have documented hyperglycemia, insulin resistance, and glucose intolerance in a seemingly increasing proportion of patients with HIV infection. Other studies have described a variety of syndromes of fat accumulation and fat loss, including abdominal obesity. Although initially attributed specifically to protease inhibitors (PI), these abnormalities also have been observed in antiretroviral-experienced but PI-naive patients. Hyperinsulinemia and abdominal obesity are strong independent risk factors for coronary artery disease. In noninfected patients, metformin and thiazolidinediones have been shown to reduce insulin resistance by different mechanisms and also to reduce visceral adiposity. This study investigates the use of metformin and rosiglitazone, a member of the thiazolidinedione class, in HIV-infected patients with hyperinsulinemia and central fat accumulation.
At study entry, clinical and laboratory assessments are performed. A standard OGTT, with plasma samples drawn over 120 minutes, will be performed for glucose and insulin determinations. After completion of entry evaluations, patients are assigned randomly to 1 of 4 double-blinded treatment arms:
Arm A: Metformin plus rosiglitazone placebo. Arm B: Metformin placebo plus rosiglitazone. Arm C: Metformin plus rosiglitazone. Arm D: Metformin placebo plus rosiglitazone placebo. Patients who are still on study drugs at Week 16 (at either full or reduced dose) are switched to the open-label phase to receive the combination of metformin and rosiglitazone through Week 32. Patients have evaluations at Weeks 2, 4, 8, 12, 16, 18, 20, 24, 28, and 32. \[AS PER AMENDMENT 02/05/02: Evaluations must be performed under fasting conditions.\] Safety indices, fasting insulin and glucose levels, visceral \[AS PER AMENDMENT 02/05/02: and subcutaneous abdominal\] fat are assessed. \[AS PER AMENDMENT 02/05/02: Patients who discontinue study treatment due to pregnancy during the study will have the Week 32 evaluations (except CT and DEXA scans).\] \[AS PER AMENDMENT 02/05/02: A mid-thigh measurement was added to the study as a secondary endpoint to look for changes in extremity subcutaneous fat from therapy with rosiglitazone. Rosiglitazone and other peroxisome proliferator-activated receptor (PPAR) gamma activators increase subcutaneous adipogenesis and may thus increase subcutaneous fat and improve insulin resistance in this way.\]
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 105
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (34)
Johns Hopkins Hosp
🇺🇸Baltimore, Maryland, United States
Ohio State Univ Hosp Clinic
🇺🇸Columbus, Ohio, United States
Vanderbilt Univ Med Ctr
🇺🇸Nashville, Tennessee, United States
Univ of Washington
🇺🇸Seattle, Washington, United States
Univ of Pennsylvania
🇺🇸Philadelphia, Pennsylvania, United States
Willow Clinic
🇺🇸Menlo Park, California, United States
Univ of Colorado Health Sciences Ctr
🇺🇸Denver, Colorado, United States
San Mateo AIDS Program / Stanford Univ
🇺🇸Stanford, California, United States
The CORE Ctr
🇺🇸Chicago, Illinois, United States
Northwestern Univ Med School
🇺🇸Chicago, Illinois, United States
Rush Presbyterian - Saint Luke's Med Ctr
🇺🇸Chicago, Illinois, United States
Methodist Hosp of Indiana / Life Care Clinic
🇺🇸Indianapolis, Indiana, United States
Wishard Hosp
🇺🇸Indianapolis, Indiana, United States
Univ of Maryland, Institute of Human Virology
🇺🇸Baltimore, Maryland, United States
Washington Univ / St Louis Connect Care
🇺🇸Saint Louis, Missouri, United States
Brigham and Women's Hosp
🇺🇸Boston, Massachusetts, United States
Bellevue Hosp / New York Univ Med Ctr
🇺🇸New York, New York, United States
Washington Univ School of Medicine
🇺🇸St Louis, Missouri, United States
Beth Israel Med Ctr
🇺🇸New York, New York, United States
Univ of Pittsburgh
🇺🇸Pittsburgh, Pennsylvania, United States
Univ of California San Francisco
🇺🇸San Francisco, California, United States
Univ of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
Univ of Southern California / LA County USC Med Ctr
🇺🇸Los Angeles, California, United States
Univ of North Carolina
🇺🇸Chapel Hill, North Carolina, United States
UCLA CARE Ctr
🇺🇸Los Angeles, California, United States
Univ of California, San Diego
🇺🇸San Diego, California, United States
Georgetown Univ Med Ctr
🇺🇸Washington, District of Columbia, United States
Stanford Univ Med Ctr
🇺🇸Stanford, California, United States
Univ of Hawaii
🇺🇸Honolulu, Hawaii, United States
Boston Med Ctr
🇺🇸Boston, Massachusetts, United States
Indiana Univ Hosp
🇺🇸Indianapolis, Indiana, United States
Univ of Cincinnati
🇺🇸Cincinnati, Ohio, United States
Harvard (Massachusetts Gen Hosp)
🇺🇸Boston, Massachusetts, United States
Univ of Nebraska Med Ctr
🇺🇸Omaha, Nebraska, United States