Clinical trial NCT00148850: Effect of Pioglitazone on HIV-1 Related Lipoatrophy: a Randomized, Double Blind, Placebo-Controlled Trial in 130 Patients
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 type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: HIV-Associated Lipodystrophy Syndrome
HIV Infections
Keywords: HIV-Associated Lipodystrophy Syndrome
pioglitazone
HIV infections
Treatment Experienced
Lead sponsor: French National Agency for Research on AIDS and Viral Hepatitis
Sponsor class: OTHER_GOV
Collaborators: name: Takeda
First posted: 2005-09-08
Enrollment: 130
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility 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

Primary outcomes:
measure: Evolution from inclusion to week 48 of limb fat using DEXA Scan (Dual Energy X-ray Absorptiometry)
Secondary outcomes:
measure: Changes from inclusion to week 48:
measure: Lipid profile and the glucidic metabolism
measure: SAT/TAT and VAT/TAT ratios evaluated with scanner
measure: X ray of L4
measure: Anthropometric measurements and the quality of life (WHO-QOL-HIV BREF)
measure: Evaluation of clinical and biological safety
Other outcomes:
Locations:
city: Paris
country: France
facility: Service des Maladies Infectieuses et Tropicales, Hopital Tenon
Study officials:
affiliation: Hopital Tenon Paris
name: Willy Rozenbaum, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: INSERM U 720
name: Dominique Costagliola
role: STUDY_CHAIR
References:
citation: Slama L, Lanoy E, Valantin MA, Bastard JP, Chermak A, Boutekatjirt A, William-Faltaos D, Billaud E, Molina JM, Capeau J, Costagliola D, Rozenbaum W. Effect of pioglitazone on HIV-1-related lipodystrophy: a randomized double-blind placebo-controlled trial (ANRS 113). Antivir Ther. 2008;13(1):67-76.