Study to Evaluate Changes in Limb Fat When Switching From a Thymidine Analogue

Lipodystrophy Clinical Trial

— RAVE  

Official title:

A Phase II, Open-Label, Multicentre, Randomised, Comparator Study of Substitution With Tenofovir or Abacavir in HIV-1 Infected Individuals, With a Viral Load < 50 Copies/mL, Receiving a Thymidine Analogue (Zidovudine or Stavudine) as Part of Their Highly Active Antiretroviral Therapy (HAART)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00647946
• Other study ID #: GS-UK-104-1008
• Status: Completed
• Phase: Phase 2
• First received: March 27, 2008
• Last updated: June 27, 2008
• Start date: February 2003
• Est. completion date: February 2006

Study information

• Verified date: June 2008
• Source: Gilead Sciences
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial Summary

A previous study substituting zidovudine or stavudine to abacavir in patients with severe or moderate lipoatrophy has shown an increase in limb fat by DEXA. This study was conducted over a 24-week period and although improved outcomes were documented by objective measures, DEXA scans, subjective observation did not correspond. Longer-term follow up of these patients is required.

This 48 week study is designed to compare the substitution of the thymidine analogues zidovudine (ZDV) or stavudine (D4T) with either tenofovir DF or abacavir, in patients treated with highly active antiretroviral therapy (HAART), and show improved outcomes on total limb fat mass, improved body shape by dual energy x-ray absorptiometry (DEXA) and computed tomography (CT) scans and improved cholesterol and triglycerides.

Description:

This is a phase II, open-label, multicentre, randomised, two-arm study of 48 weeks duration. One hundred HIV infected individuals who have documented lipodystrophy at > 1 body/facial site and currently receiving zidovudine (ZDV) or stavudine (d4T) will be recruited.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 100
• Est. completion date: February 2006
• Est. primary completion date: October 2004
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Subjects who are male or female > 18 years of age

• Subjects who are HIV-1 infected as documented by a licensed HIV-1 antibody ELISA

• Female subjects of childbearing potential must have a negative serum pregnancy test (beta-HCG) within 28 days of trial day 1. Women of childbearing potential must agree to use a barrier method of contraception

• Female subjects must not be pregnant or lactating

• Subjects who in the opinion of the investigator have the ability to understand and provided written informed consent to participate in the trial

• Subjects who in the opinion of the investigator have clinical lipoatrophy at > 1 body/facial site

• Subjects currently receiving nucleoside analogue regimen including stavudine (d4T) or zidovudine (ZDV)

• Subjects who are stable on current therapy for >16 weeks

• Subjects with no prior exposure to tenofovir, abacavir, or adefovir

• Subjects with no known K65R, 69S mutations or 3 or more thymidine analogue mutations

• Subjects with documented viral load <50 copies/ml on 2 consecutive occasions including most recent clinic attendance

Exclusion Criteria:

• Subjects who in the investigator's opinion are unlikely to complete the 48 week trial period

• Currently active opportunistic disease or documented wasting syndrome

• Currently receiving chemotherapy for malignancy

• Subjects who in the opinion of the investigator are unlikely to retain viral response after switching based on treatment or transmission history

• Currently receiving an insulin sensitising agent (glitazone or metformin)

• Anabolic steroids in the last 16 weeks other than testosterone at replacement doses (<250mg/2 weekly)

• Growth hormone use in the last 16 weeks

• Statin therapy (HMG CoA reductase inhibitor) commenced in the last 16 weeks (patients stable on statins my be included)

• Current alcohol or illicit drug use which, in the opinion of the investigator, may interfere with the subjects' ability to comply with the dosing schedule and protocol evaluations

• Receiving concurrent medications that - in the opinion of the investigator and according to drug product labelling - will result in clinically significant interactions with tenofovir or abacavir

• Pregnant or breast feeding

• Previously received more than 3 months zidovudine monotherapy

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Lipodystrophy

Intervention

Drug:
• tenofovir DF
tenofovir DF 300mg once daily along with the other antiviral drugs
• abacavir 300mg twice daily
abacavir 300mg twice daily along with the other antiviral drugs

Locations

Country	Name	City	State
United Kingdom	Gilead Sciences	Abingdon	Cambridge

Sponsors (1)

Lead Sponsor	Collaborator
Gilead Sciences

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in total limb fat mass by DEXA scan		24 and 48 weeks	No
Secondary	Change in VAT by single slice L4 abdominal CT scan		24 and 48 weeks	No
Secondary	Change in viral load measurements and CD4 cell count		24 and 48 Weeks	No
Secondary	Change in fasting cholesterol and triglycerides		24 and 48 Weeks	No
Secondary	Change in blood insulin and fasting glucose		24 and 48 Weeks	No
Secondary	Change in blood lactate and anion gap		24 and 48 Weeks	No
Secondary	Change in bone mineral density by DEXA scan		24 and 48 Weeks	No
Secondary	Incidence of adverse events		Upto 48 weeks	No