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| Sponsor: | National Institute of Allergy and Infectious Diseases (NIAID) |
|---|---|
| Information provided by: | National Institute of Allergy and Infectious Diseases (NIAID) |
| ClinicalTrials.gov Identifier: | NCT00015691 |
Purpose
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.
| Condition | Intervention |
|---|---|
|
HIV Infections Lipodystrophy Hyperinsulinemia |
Drug: Metformin hydrochloride Drug: Rosiglitazone maleate |
| Study Type: | Interventional |
| Study Design: | Treatment, Double-Blind, Safety Study |
| Official Title: | A Randomized, Double-Blind, Placebo-Controlled Study of Metformin and Rosiglitazone, Alone or in Combination, in HIV-Infected Subjects With Hyperinsulinemia and Elevated Waist/Hip Ratio |
| Estimated Enrollment: | 105 |
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.]
Eligibility| Ages Eligible for Study: | 18 Years to 65 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria
Patients may be eligible for this study if they:
Exclusion Criteria
Patients will not be eligible for this study if they:
Contacts and Locations
Hide Study Locations| United States, Alabama | |
| Univ of Alabama at Birmingham | |
| Birmingham, Alabama, United States, 35294 | |
| United States, California | |
| Stanford Univ Med Ctr | |
| Stanford, California, United States, 943055107 | |
| UCLA CARE Ctr | |
| Los Angeles, California, United States, 90095 | |
| Univ of Southern California / LA County USC Med Ctr | |
| Los Angeles, California, United States, 900331079 | |
| Univ of California, San Diego | |
| San Diego, California, United States, 92103 | |
| Willow Clinic | |
| Menlo Park, California, United States, 94025 | |
| Univ of California San Francisco | |
| San Francisco, California, United States, 94110 | |
| San Mateo AIDS Program / Stanford Univ | |
| Stanford, California, United States, 943055107 | |
| United States, Colorado | |
| Univ of Colorado Health Sciences Ctr | |
| Denver, Colorado, United States, 80262 | |
| United States, District of Columbia | |
| Georgetown Univ Med Ctr | |
| Washington, District of Columbia, United States, 20007 | |
| United States, Hawaii | |
| Univ of Hawaii | |
| Honolulu, Hawaii, United States, 96816 | |
| United States, Illinois | |
| Northwestern Univ Med School | |
| Chicago, Illinois, United States, 60611 | |
| Rush Presbyterian - Saint Luke's Med Ctr | |
| Chicago, Illinois, United States, 60612 | |
| The CORE Ctr | |
| Chicago, Illinois, United States, 60612 | |
| United States, Indiana | |
| Indiana Univ Hosp | |
| Indianapolis, Indiana, United States, 462025250 | |
| Methodist Hosp of Indiana / Life Care Clinic | |
| Indianapolis, Indiana, United States, 46202 | |
| Wishard Hosp | |
| Indianapolis, Indiana, United States, 46202 | |
| United States, Maryland | |
| Johns Hopkins Hosp | |
| Baltimore, Maryland, United States, 21287 | |
| Univ of Maryland, Institute of Human Virology | |
| Baltimore, Maryland, United States, 21201 | |
| United States, Massachusetts | |
| Harvard (Massachusetts Gen Hosp) | |
| Boston, Massachusetts, United States, 02114 | |
| Boston Med Ctr | |
| Boston, Massachusetts, United States, 02118 | |
| Brigham and Women's Hosp | |
| Boston, Massachusetts, United States, 02215 | |
| United States, Missouri | |
| Washington Univ School of Medicine | |
| St Louis, Missouri, United States, 63108 | |
| Washington Univ / St Louis Connect Care | |
| Saint Louis, Missouri, United States, 63108 | |
| United States, Nebraska | |
| Univ of Nebraska Med Ctr | |
| Omaha, Nebraska, United States, 681985130 | |
| United States, New York | |
| Bellevue Hosp / New York Univ Med Ctr | |
| New York, New York, United States, 10016 | |
| Beth Israel Med Ctr | |
| New York, New York, United States, 10003 | |
| United States, North Carolina | |
| Univ of North Carolina | |
| Chapel Hill, North Carolina, United States, 275997215 | |
| United States, Ohio | |
| Univ of Cincinnati | |
| Cincinnati, Ohio, United States, 452670405 | |
| Ohio State Univ Hosp Clinic | |
| Columbus, Ohio, United States, 432101228 | |
| United States, Pennsylvania | |
| Univ of Pittsburgh | |
| Pittsburgh, Pennsylvania, United States, 15213 | |
| Univ of Pennsylvania | |
| Philadelphia, Pennsylvania, United States, 19104 | |
| United States, Tennessee | |
| Vanderbilt Univ Med Ctr | |
| Nashville, Tennessee, United States, 37203 | |
| United States, Washington | |
| Univ of Washington | |
| Seattle, Washington, United States, 98104 | |
| Study Chair: | Kathleen Mulligan | |
| Study Chair: | Steven Grinspoon |
More Information
| Study ID Numbers: | ACTG A5082, AACTG A5082 |
| Study First Received: | May 1, 2001 |
| Last Updated: | August 6, 2008 |
| ClinicalTrials.gov Identifier: | NCT00015691 History of Changes |
| Health Authority: | United States: Federal Government |
|
Drug Therapy, Combination Adipose Tissue Area Under Curve Hypoglycemic Agents Anthropometry |
Hyperinsulinemia Metformin BRL 49653 Insulin Glucose Tolerance Test |
|
RNA Virus Infections Sexually Transmitted Diseases, Viral Metabolic Diseases Slow Virus Diseases Skin Diseases Immune System Diseases Physiological Effects of Drugs Metformin Acquired Immunodeficiency Syndrome Infection Pharmacologic Actions Immunologic Deficiency Syndromes |
Virus Diseases Hyperinsulinism Hypoglycemic Agents Skin Diseases, Metabolic HIV Infections Lipodystrophy Sexually Transmitted Diseases Lentivirus Infections Glucose Metabolism Disorders Rosiglitazone Retroviridae Infections Lipid Metabolism Disorders |