HIV InfectionsNCT00015691
Metformin and Rosiglitazone, Alone or in Combination, in HIV-Infected Patients With Insulin and Fat Abnormalities
A study testing Metformin hydrochloride and Rosiglitazone maleate in people with HIV Infections and Lipodystrophy, run by National Institute of Allergy and Infectious Diseases (NIAID) at 34 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- HIV Infections, Lipodystrophy, Hyperinsulinemia
- What is being tested?
- Metformin hydrochloride and Rosiglitazone maleate
- How many people
- 105 participants
- Where
- 34 sitesUnited States
- Study dates
- Start not givento Jan 2006
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
34 sites in 1 country.
34 sites in 1 country
United States34 sites
Univ of Maryland, Institute of Human Virology
Baltimore, Maryland, 21201
Johns Hopkins Hosp
Baltimore, Maryland, 21287
Univ of Alabama at Birmingham
Birmingham, Alabama, 35294
Harvard (Massachusetts Gen Hosp)
Boston, Massachusetts, 02114
Boston Med Ctr
Boston, Massachusetts, 02118
Brigham and Women's Hosp
Boston, Massachusetts, 02215
Univ of North Carolina
Chapel Hill, North Carolina, 275997215
Northwestern Univ Med School
Chicago, Illinois, 60611
Rush Presbyterian - Saint Luke's Med Ctr
Chicago, Illinois, 60612
The CORE Ctr
Chicago, Illinois, 60612
Univ of Cincinnati
Cincinnati, Ohio, 452670405
Ohio State Univ Hosp Clinic
Columbus, Ohio, 432101228
Univ of Colorado Health Sciences Ctr
Denver, Colorado, 80262
Univ of Hawaii
Honolulu, Hawaii, 96816
Indiana Univ Hosp
Indianapolis, Indiana, 462025250
Methodist Hosp of Indiana / Life Care Clinic
Indianapolis, Indiana, 46202
Wishard Hosp
Indianapolis, Indiana, 46202
Univ of Southern California / LA County USC Med Ctr
Los Angeles, California, 900331079
UCLA CARE Ctr
Los Angeles, California, 90095
Willow Clinic
Menlo Park, California, 94025
Vanderbilt Univ Med Ctr
Nashville, Tennessee, 37203
Beth Israel Med Ctr
New York, New York, 10003
Bellevue Hosp / New York Univ Med Ctr
New York, New York, 10016
Univ of Nebraska Med Ctr
Omaha, Nebraska, 681985130
Univ of Pennsylvania
Philadelphia, Pennsylvania, 19104
Univ of Pittsburgh
Pittsburgh, Pennsylvania, 15213
Univ of California, San Diego
San Diego, California, 92103
Univ of California San Francisco
San Francisco, California, 94110
Univ of Washington
Seattle, Washington, 98104
Washington Univ / St Louis Connect Care
St Louis, Missouri, 63108
Washington Univ School of Medicine
St Louis, Missouri, 63108
San Mateo AIDS Program / Stanford Univ
Stanford, California, 943055107
Stanford Univ Med Ctr
Stanford, California, 943055107
Georgetown Univ Med Ctr
Washington D.C., District of Columbia, 20007
About this 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
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.
Read the 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.]
- Conditions
- HIV Infections, Lipodystrophy, Hyperinsulinemia
- Being tested
- Metformin hydrochloride, Rosiglitazone maleate
- Keywords
- Drug Therapy, Combination, Adipose Tissue, Area Under Curve, Hypoglycemic Agents, Anthropometry, Hyperinsulinemia, Metformin, BRL 49653, Insulin, Glucose Tolerance Test
- Medical subject headings
- HIV Infections, Lipodystrophy, Hyperinsulinism, Insulin Resistance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Metformin hydrochlorideDrug
Rosiglitazone maleateDrug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Aug 2001 (estimated)
- Primary completionJan 2006
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HIV InfectionsStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Masking
- Double blind
- Enrolment
- 105 participants
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Kathleen Mulligan, Study chairSteven Grinspoon, Study chair
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00015691
- Sponsor's protocol ID
- A5082
- Other IDs
- AACTG A5082, ACTG A5082, 10913
- Status last verified
- Jul 2013
- First submitted
- 1 May 2001
- Last updated
- 22 Jul 2013
- Results posted
- No
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. doi: 10.1210/jc.2002-020709.
PubMed 12364443
Study at a glance
From the registry record, last updated by the sponsor on 22 Jul 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00015691
- Acronym / sponsor ID
- A5082
- Conditions
- HIV Infections, Lipodystrophy, Hyperinsulinemia
- Keywords
- Drug Therapy, Combination, Adipose Tissue, Area Under Curve, Hypoglycemic Agents, Anthropometry, Hyperinsulinemia, Metformin, BRL 49653
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 105 participants
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Primary completion
- Jan 2006 (actual)
- First posted
- 31 Aug 2001 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.]
Study design
- Primary purpose
- Treatment
- Masking
- Double blind
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- 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.
Key exclusion criteria (10 listed)
- Are allergic to metformin or rosiglitazone.
- Are pregnant or breast-feeding.
- Abuse drugs or alcohol.
- Have diarrhea, nausea, or vomiting.
- Have heart disease.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Metformin hydrochloride | Drug | – |
| Rosiglitazone maleate | Drug | – |
Primary outcome
Not reported in the source record.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jul 2013.
- Background: PubMed 12364443Hadigan 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. doi: 10.1210/jc.2002-020709.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Kathleen Mulligan study chair
Steven Grinspoon study chair
34 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Metformin hydrochloride and Rosiglitazone maleate in people with HIV Infections and Lipodystrophy, run by National Institute of Allergy and Infectious Diseases (NIAID) at 34 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Jul 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 34 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00015691, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jul 2013.