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

This study has been completed.
Sponsor:
Information provided by:
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT00647946
First received: March 27, 2008
Last updated: June 27, 2008
Last verified: June 2008
  Purpose

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.


Condition Intervention Phase
Lipodystrophy
Drug: tenofovir DF
Drug: abacavir 300mg twice daily
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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)

Resource links provided by NLM:


Further study details as provided by Gilead Sciences:

Primary Outcome Measures:
  • Change in total limb fat mass by DEXA scan [ Time Frame: 24 and 48 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Change in VAT by single slice L4 abdominal CT scan [ Time Frame: 24 and 48 weeks ] [ Designated as safety issue: No ]
  • Change in viral load measurements and CD4 cell count [ Time Frame: 24 and 48 Weeks ] [ Designated as safety issue: No ]
  • Change in fasting cholesterol and triglycerides [ Time Frame: 24 and 48 Weeks ] [ Designated as safety issue: No ]
  • Change in blood insulin and fasting glucose [ Time Frame: 24 and 48 Weeks ] [ Designated as safety issue: No ]
  • Change in blood lactate and anion gap [ Time Frame: 24 and 48 Weeks ] [ Designated as safety issue: No ]
  • Change in bone mineral density by DEXA scan [ Time Frame: 24 and 48 Weeks ] [ Designated as safety issue: No ]
  • Incidence of adverse events [ Time Frame: Upto 48 weeks ] [ Designated as safety issue: No ]

Enrollment: 100
Study Start Date: February 2003
Study Completion Date: February 2006
Primary Completion Date: October 2004 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: A
Stop zidovudine (ZDV) or stavudine (d4T) and start tenofovir DF 300mg once daily along with the other antiviral drugs that are used as part of their HAART regimen
Drug: tenofovir DF
tenofovir DF 300mg once daily along with the other antiviral drugs
Active Comparator: B
Stop zidovudine (ZDV) or stavudine (d4T) and start abacavir 300mg twice daily along with the other antiviral drugs that are used as part of their HAART regimen
Drug: abacavir 300mg twice daily
abacavir 300mg twice daily along with the other antiviral drugs

Detailed 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00647946

Locations
United Kingdom
Gilead Sciences
Abingdon, Cambridge, United Kingdom, CB1 6GT
Sponsors and Collaborators
Gilead Sciences
Investigators
Study Director: Geoff Cotton Gilead Sciences
  More Information

Additional Information:
No publications provided

Responsible Party: Geoff Cotton, Medical Monitor, Gilead Sciences
ClinicalTrials.gov Identifier: NCT00647946     History of Changes
Other Study ID Numbers: GS-UK-104-1008
Study First Received: March 27, 2008
Last Updated: June 27, 2008
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Gilead Sciences:
lipodystrophy

Additional relevant MeSH terms:
Lipodystrophy
Skin Diseases, Metabolic
Skin Diseases
Lipid Metabolism Disorders
Metabolic Diseases
Tenofovir
Tenofovir disoproxil
Abacavir
Antiviral Agents
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-Retroviral Agents
Anti-Infective Agents
Therapeutic Uses
Anti-HIV Agents

ClinicalTrials.gov processed this record on September 16, 2014