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

HIV Infections Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00148850
• Other study ID #: ANRS 113 LIPIOT
• Status: Terminated
• Phase: Phase 3
• First received: September 7, 2005
• Last updated: October 19, 2005
• Start date: February 2003
• Est. completion date: October 2004

Study information

• Verified date: September 2005
• Source: French National Agency for Research on AIDS and Viral Hepatitis
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 130
• Est. completion date: October 2004
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Treatment

Related Conditions & MeSH terms

• HIV Infections
• HIV-Associated Lipodystrophy Syndrome
• Lipodystrophy

Intervention

Drug:
• Pioglitazone

Locations

Country	Name	City	State
France	Service des Maladies Infectieuses et Tropicales, Hopital Tenon	Paris

Sponsors (2)

Lead Sponsor	Collaborator
French National Agency for Research on AIDS and Viral Hepatitis	Takeda

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Evolution from inclusion to week 48 of limb fat using DEXA Scan (Dual Energy X-ray Absorptiometry)
Secondary	Changes from inclusion to week 48:
Secondary	Lipid profile and the glucidic metabolism
Secondary	SAT/TAT and VAT/TAT ratios evaluated with scanner
Secondary	X ray of L4
Secondary	Anthropometric measurements and the quality of life (WHO-QOL-HIV BREF)
Secondary	Evaluation of clinical and biological safety