Study to Evaluate Changes in Limb Fat When Switching From a Thymidine Analogue (RAVE)
This study has been completed.
Sponsor:
Gilead Sciences
Information provided by:
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT00647946
First received: March 27, 2008
Last updated: June 27, 2008
Last verified: June 2008
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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:
Drug Information available for:
Stavudine
Zidovudine
Abacavir
Tenofovir
Abacavir sulfate
Tenofovir Disoproxil Fumarate
U.S. FDA Resources
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 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 Antiviral Agents Tenofovir Tenofovir disoproxil Abacavir Dideoxynucleosides |
Anti-Infective Agents Therapeutic Uses Pharmacologic Actions Reverse Transcriptase Inhibitors Nucleic Acid Synthesis Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Anti-Retroviral Agents Anti-HIV Agents Antimetabolites |
ClinicalTrials.gov processed this record on May 22, 2013