Effect of Pioglitazone on HIV-1 Related Lipoatrophy: a Randomized, Double Blind, Placebo-Controlled Trial in 130 Patients

Study Overview
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Brief Summary
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The aim of this randomized study is to compare the effect of pioglitazone versus placebo on change in limb fat in HIV 1-infected patients treated with antiretroviral therapy for at least 6 months and with clinical lipoatrophy.

Detailed Description
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Lipodystrophy is one of the most frequent treatment side effect in HIV-1 infected patients. This complication can be stigmatizing in some affected patients and lead to reduced adherence to treatment, increased risk of cardiovascular complications and induce insulinoresistance. The pathophysiology of lipodystrophy remains poorly understood. Some antiretroviral drugs could be involved. Therefore, using PPAR G as a therapeutic target with the objective to reverse drug induced lipoatrophy appeared as a promising objective Thiazolidinediones are a new class of insulin sensitizing drugs for the treatment of type 2 diabetes. These PPARG agonist which mainly promote the differentiation of adipocytes, decrease circulating plasma free fatty acids. In non-HIV infected patients this class of drugs decreases intraabdominal fat accumulation and increases subcutaneous fat depot. Different previous studies were performed with that aim, most of them using rosiglitazone. We designed a prospective randomized, double blind placebo controlled multicentre study aiming to test the hypothesis that pioglitazone would improve lipoatrophy without deleterious effect on lipid profile in adult subjects receiving antiretroviral therapy.

Official Title
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A Randomized, Phase 3, Double Blind, Multicentre Trial, Evaluating the Effect of Pioglitazone Versus Placebo on Change in Lipoatrophy in HIV- 1 Infected Patients Treated With Stable Antiretroviral Therapy for at Least 6 Months.ANRS 113 LIPIOT Study

Conditions
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HIV-Associated Lipodystrophy Syndrome, HIV Infections

Intervention / Treatment
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* Drug: Pioglitazone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 years of ages and older Confirmed laboratory diagnosis of HIV-1-infection Karnofsky equal or over 70% Patients treated with stable antiretroviral therapy for at least 6 months Plasma viral load below 400 copies/ ml and CD4 count over 200/mm3 for at least 6 months Patients with a clinical peripheral lipoatrophy self reported by the patient and confirmed by physical examination Exclusion Criteria: Cachexia Cardiac failure class3 or 4 at NYHA classification Acute opportunistic infection Pregnancy or breast-feeding Polynuclear neutrophils below 1000/mm3 Hemoglobin below 9 g/dl Platelets below 50 000/mm3 Creatinine level over 2 UN ASAT, ALAT over 2.5UN Bilirubin, amylase, lipase level over 2 UN CD4 count below 200/mm3 Patients treated by any antidiabetic or lipid lowering drugs, anabolic or corticosteroid hormone

Ages Eligible for Study
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Minimum Age: 18 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: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Pioglitazone|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evolution from inclusion to week 48 of limb fat using DEXA Scan (Dual Energy X-ray Absorptiometry) |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes from inclusion to week 48: |  |  | 
| Lipid profile and the glucidic metabolism |  |  | 
| SAT/TAT and VAT/TAT ratios evaluated with scanner |  |  | 
| X ray of L4 |  |  | 
| Anthropometric measurements and the quality of life (WHO-QOL-HIV BREF) |  |  | 
| Evaluation of clinical and biological safety |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV-Associated Lipodystrophy Syndrome, pioglitazone, HIV infections, Treatment Experienced