HIV Infection, Lipodystrophy
Conditions
Keywords
Lipodystrophy, Insulin resistance, HIV infection
Brief summary
The purpose of this study is to examine the relationship between insulin resistance and changes in body fat distribution in HIV-infected persons. This study measures insulin sensitivity, abdominal fat, and intramuscular fat in HIV-infected persons and examines the effect of an anti-diabetic drug (metformin or pioglitazone) on insulin sensitivity and body fat in this population.
Detailed description
Although HIV antiretroviral medications have helped patients live longer, they have also been associated with side effects including insulin resistance and changes in body fat distribution. Changes in body fat distribution associated with HIV antiretroviral medications may result in increased fat in the abdomen, neck, and upper back, which is often called central fat deposition. HIV antiretroviral medications may also result in loss of fat in legs, arms, and face, which is often called peripheral fat atrophy. This study will obtain preliminary data on the effect of 12 weeks of metformin on insulin sensitivity and hepatic and peripheral muscle fat in HIV-infected persons with insulin resistance and central fat deposition. Similarly, this study will obtain preliminary data on the effect of 12 weeks of pioglitazone on insulin sensitivity and hepatic and peripheral muscle fat in HIV-infected persons with insulin resistance and peripheral fat atrophy. This study involves taking a drug that has been approved by the U.S. Food and Drug Administration (FDA) for use in humans for a period of 3 months.
Interventions
DRUGMetformin
Metformin at a dose of one 500mg tablet twice a day with meals for one week, after which the dose will increase to 500 mg three times a day with meals for the remaining 11 weeks of the study.
DRUGPioglitazone
Pioglitazone at a dose of one 30 mg tablet once per day for the 12 weeks of the study.
Sponsors
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Tufts Medical Center
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Age 18-70 years * Fasting insulin \>12 μU/mL and/or serum glucose between 140-200 mg/dl after 75 g 2hr oral glucose tolerance test * Central fat deposition or Peripheral fat atrophy * Fasting glucose ≤126 mg/dL * BMI ≥18 and ≤35 kg/m2 * CD4 cell count ≥100 cells/mm3 * Stable antiretroviral regimen ≥12 weeks and HIV RNA \<1000 copies
Exclusion criteria
* Diabetes mellitus * Cardiac pacemaker or metal implant * Liver enzymes \>2.5x upper normal limit * Alkaline phosphatase or prothrombin time \>2x upper normal limit * Serum creatinine \>1.4 mg/dL * History of congestive heart failure * Hemoglobin \<8 g/dL * Alcohol abuse * Pregnancy * History of lactic acidosis * Use of steroids * Acute infection within last one month * History of bladder cancer
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Insulin Sensitivity From Baseline to Week 12 Post-treatment With Insulin Sensitizing Agent | 3 months | Change in insulin sensitivity measured by 2 hour euglycemic-hyperinsulinemic clamp from baseline to week 12 post treatment with metformin or pioglitazone |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Hepatic Fat From Baseline to Week 12 Post-treatment With an Insulin Sensitizing Agent | 12 weeks | Change in hepatic fat was measured after 12 weeks of treatment with metformin or pioglitazone using magnetic resonance spectroscopy |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Metformin Metformin: Metformin at a dose of one 500mg tablet twice a day with meals for one week, after which the dose will increase to 500 mg three times a day with meals for the remaining 11 weeks of the study. | 16 |
| Pioglitazone Pioglitazone: Pioglitazone at a dose of one 30 mg tablet once per day for the 12 weeks of the study. | 4 |
| Total | 20 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 5 | 1 |
Baseline characteristics
| Characteristic | Metformin | Pioglitazone | Total |
|---|---|---|---|
| Age, Continuous | 53.9 years STANDARD_DEVIATION 7.9 | 55.7 years STANDARD_DEVIATION 8.6 | 54.2 years STANDARD_DEVIATION 7.8 |
| Sex: Female, Male Female | 4 Participants | 0 Participants | 4 Participants |
| Sex: Female, Male Male | 12 Participants | 4 Participants | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 4 / 16 | 1 / 4 |
| serious Total, serious adverse events | 7 / 16 | 0 / 4 |
Outcome results
Primary
Change in Insulin Sensitivity From Baseline to Week 12 Post-treatment With Insulin Sensitizing Agent
Change in insulin sensitivity measured by 2 hour euglycemic-hyperinsulinemic clamp from baseline to week 12 post treatment with metformin or pioglitazone
Time frame: 3 months
Population: Only participants with baseline and post insulin-sensitizing treatment euglycemic-hyperinsulinemic clamp were included in this analysis
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Metformin | Change in Insulin Sensitivity From Baseline to Week 12 Post-treatment With Insulin Sensitizing Agent | -0.25 mg/kg lean body mass/min | Standard Deviation 1.98 |
| Pioglitazone | Change in Insulin Sensitivity From Baseline to Week 12 Post-treatment With Insulin Sensitizing Agent | -0.96 mg/kg lean body mass/min | Standard Deviation 0.43 |
Secondary
Change in Hepatic Fat From Baseline to Week 12 Post-treatment With an Insulin Sensitizing Agent
Change in hepatic fat was measured after 12 weeks of treatment with metformin or pioglitazone using magnetic resonance spectroscopy
Time frame: 12 weeks
Population: Only participants with baseline and post insulin sensitizing treatment magnetic resonance spectrosocpy were included in this analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Metformin | Change in Hepatic Fat From Baseline to Week 12 Post-treatment With an Insulin Sensitizing Agent | 2.30 percentage of hepatic fat | Standard Deviation 2.1 |
| Pioglitazone | Change in Hepatic Fat From Baseline to Week 12 Post-treatment With an Insulin Sensitizing Agent | -2.56 percentage of hepatic fat | Standard Deviation 1.16 |