Metabolic Abnormalities in HIV-infected Persons

Study Overview
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Brief Summary
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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
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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.

Official Title
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Metabolic Abnormalities in HIV-infected Persons

Conditions
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Lipodystrophy, HIV Infection

Intervention / Treatment
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* Drug: Metformin
* Drug: Pioglitazone


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Metformin<br> | Drug: Metformin<br>* 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.<br>* Other names: Riomet;|
| Experimental: Pioglitazone<br> | Drug: Pioglitazone<br>* Pioglitazone at a dose of one 30 mg tablet once per day for the 12 weeks of the study.<br>* Other names: Actos;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Lipodystrophy, Insulin resistance, HIV infection