Metformin and Rosiglitazone, Alone or in Combination, in HIV-Infected Patients With Insulin and Fat Abnormalities
Condition: HIV Infections; Lipodystrophy; Hyperinsulinemia
MeSH terms: Lipodystrophy; Hyperinsulinism
Study type: Interventional

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.]
    

Intervention name(s): Metformin hydrochloride; Rosiglitazone maleate
Intervention type(s): Drug; Drug
Intervention MeSH terms: Metformin; Rosiglitazone
Masking: Double
Primary purpose: Treatment
Keywords: Drug Therapy, Combination; Adipose Tissue; Area Under Curve; Hypoglycemic Agents; Anthropometry; Hyperinsulinemia; Metformin; BRL 49653; Insulin; Glucose Tolerance Test