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

Condition(s) targeted: HIV-Associated Lipodystrophy Syndrome; HIV Infections

Intervention: Pioglitazone (Drug)

Phase: Phase 3

Status: Terminated

Sponsored by: French National Agency for Research on AIDS and Viral Hepatitis

Official(s) and/or principal investigator(s):
Willy Rozenbaum, MD, Principal Investigator, Affiliation: Hopital Tenon Paris
Dominique Costagliola, Study Chair, Affiliation: INSERM U 720

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.

Official title: 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

Study design: Treatment, Randomized, Double-Blind, Placebo Control, Parallel Assignment, Efficacy Study

Primary outcome: Evolution from inclusion to week 48 of limb fat using DEXA Scan (Dual Energy X-ray Absorptiometry)

Secondary outcome:

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

Detailed description: 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.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

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

Service des Maladies Infectieuses et Tropicales, Hopital Tenon, Paris 75020, France

Starting date: February 2003
Ending date: October 2004
Last updated: October 19, 2005