Metformin and Rosiglitazone, Alone or in Combination, in HIV-Infected Patients With Insulin and Fat Abnormalities
Information source: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov processed this data on August 20, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: HIV Infections; Lipodystrophy; Hyperinsulinemia
Intervention: Metformin hydrochloride (Drug); Rosiglitazone maleate (Drug)
Phase: N/A
Status: Completed
Sponsored by: National Institute of Allergy and Infectious Diseases (NIAID) Official(s) and/or principal investigator(s): Kathleen Mulligan, Study Chair Steven Grinspoon, Study Chair
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.
Clinical Details
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
Study design: Endpoint Classification: Safety Study, Masking: Double-Blind, Primary Purpose: Treatment
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.]
Eligibility
Minimum age: 18 Years.
Maximum age: 65 Years.
Gender(s): Both.
Criteria:
Inclusion Criteria
Patients may be eligible for this study if they:
- Are HIV-positive.
- Have a viral load (level of HIV in the blood) below 10,000 copies/ml, within 30 days
before study entry.
- Have a fasting blood insulin level at 15 micro IU/ml or greater; or a 2-hour insulin
at least 75 micro IU/ml or greater following 75 g glucose load; or a 2-hour glucose
greater than 140 mg/dl following 75 g glucose load AND fasting serum insulin at least
10 micro IU/ml or greater, within 30 days before study entry.
- Meet physical restrictions based on the amount and location of body fat and also on
height and weight.
- Have noticed changes in the location of their body fat during the course of their HIV
disease.
- Are 18 to 65 years old.
- Have taken the same anti-HIV drugs for at least 60 days before study entry and do not
plan to change these drugs for the entire study.
- If taking hormones, have been on the same treatment for at least 6 months before
study entry and do not plan to change for the entire study. Hormones include birth
control pills, estrogen, or progestin for women and testosterone for men. If hormones
were taken and then stopped, the treatment must have ended at least 6 months before
the patient enters the study.
- Have a negative pregnancy test within 30 days before taking the study drugs, if
female and able to have children.
- Agree to avoid trying to become pregnant or causing someone to become pregnant. Agree
not to donate sperm or participate in other fertilization procedures. If sexually
active, agree to use [AS PER AMENDMENT 02/05/02: 1] effective method of birth control
while taking the study medications and for at least 30 days after stopping the study
medications. Women who are not able to give birth or whose male partner is sterile
are not required to use birth control.
- Several changes have been made to this study. In earlier versions, a fasting blood
insulin above 15 micro IU/ml was the only level accepted. Now there are several other
insulin/glucose levels included. In addition, the timing of pregnancy tests has
changed from 14 days to 30 days.
Exclusion Criteria
Patients will not be eligible for this study if they:
- Are allergic to metformin or rosiglitazone.
- Are pregnant or breast-feeding.
- Abuse drugs or alcohol.
- Have diarrhea, nausea, or vomiting.
- Have heart disease.
- Are taking or have taken drugs to control blood sugar.
- Have taken any of the following drugs within 6 months before study entry: high-dose
estrogen, high-dose testosterone, high-dose testosterone gel, testosterone creams,
growth hormone, steroids to increase body size, DHEA or androstenedione (sold over
the counter), prednisone and other steroid drugs at high doses, drugs to increase
appetite, experimental drugs to increase appetite or weight gain, drugs that affect
the immune system, pentoxifylline, thalidomide, niacin (a multivitamin containing
niacin is okay), hydroxyurea, and cimetidine.
- Are taking ritonavir with simvastatin or lovastatin (drugs to lower cholesterol).
- Are taking drugs not approved by the FDA or of unknown identity, in experimental
studies.
Locations and Contacts
Univ of Alabama at Birmingham, Birmingham, Alabama 35294, United States
UCLA CARE Ctr, Los Angeles, California 90095, United States
Univ of Southern California / LA County USC Med Ctr, Los Angeles, California 900331079, United States
Willow Clinic, Menlo Park, California 94025, United States
Univ of California, San Diego, San Diego, California 92103, United States
Univ of California San Francisco, San Francisco, California 94110, United States
San Mateo AIDS Program / Stanford Univ, Stanford, California 943055107, United States
Stanford Univ Med Ctr, Stanford, California 943055107, United States
Univ of Colorado Health Sciences Ctr, Denver, Colorado 80262, United States
Georgetown Univ Med Ctr, Washington, District of Columbia 20007, United States
Univ of Hawaii, Honolulu, Hawaii 96816, United States
Northwestern Univ Med School, Chicago, Illinois 60611, United States
Rush Presbyterian - Saint Luke's Med Ctr, Chicago, Illinois 60612, United States
The CORE Ctr, Chicago, Illinois 60612, United States
Indiana Univ Hosp, Indianapolis, Indiana 462025250, United States
Methodist Hosp of Indiana / Life Care Clinic, Indianapolis, Indiana 46202, United States
Wishard Hosp, Indianapolis, Indiana 46202, United States
Johns Hopkins Hosp, Baltimore, Maryland 21287, United States
Univ of Maryland, Institute of Human Virology, Baltimore, Maryland 21201, United States
Boston Med Ctr, Boston, Massachusetts 02118, United States
Brigham and Women's Hosp, Boston, Massachusetts 02215, United States
Harvard (Massachusetts Gen Hosp), Boston, Massachusetts 02114, United States
Washington Univ / St Louis Connect Care, Saint Louis, Missouri 63108, United States
Washington Univ School of Medicine, St Louis, Missouri 63108, United States
Univ of Nebraska Med Ctr, Omaha, Nebraska 681985130, United States
Bellevue Hosp / New York Univ Med Ctr, New York, New York 10016, United States
Beth Israel Med Ctr, New York, New York 10003, United States
Univ of North Carolina, Chapel Hill, North Carolina 275997215, United States
Univ of Cincinnati, Cincinnati, Ohio 452670405, United States
Ohio State Univ Hosp Clinic, Columbus, Ohio 432101228, United States
Univ of Pennsylvania, Philadelphia, Pennsylvania 19104, United States
Univ of Pittsburgh, Pittsburgh, Pennsylvania 15213, United States
Vanderbilt Univ Med Ctr, Nashville, Tennessee 37203, United States
Univ of Washington, Seattle, Washington 98104, United States
Additional Information
Haga clic aquí para ver información sobre este ensayo clínico en español.
Related publications: Hadigan C, Rabe J, Grinspoon S. Sustained benefits of metformin therapy on markers of cardiovascular risk in human immunodeficiency virus-infected patients with fat redistribution and insulin resistance. J Clin Endocrinol Metab. 2002 Oct;87(10):4611-5.
Last updated: July 19, 2013
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