Study to Evaluate Changes in Limb Fat When Switching From a Thymidine Analogue (RAVE)
Primary Purpose
Lipodystrophy
Status
Completed
Phase
Phase 2
Locations
United Kingdom
Study Type
Interventional
Intervention
tenofovir DF
abacavir 300mg twice daily
Sponsored by
About this trial
This is an interventional treatment trial for Lipodystrophy focused on measuring lipodystrophy
Eligibility 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
Sites / Locations
- Gilead Sciences
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
A
B
Arm Description
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
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
Outcomes
Primary Outcome Measures
Change in total limb fat mass by DEXA scan
Secondary Outcome Measures
Change in VAT by single slice L4 abdominal CT scan
Change in viral load measurements and CD4 cell count
Change in fasting cholesterol and triglycerides
Change in blood insulin and fasting glucose
Change in blood lactate and anion gap
Change in bone mineral density by DEXA scan
Incidence of adverse events
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00647946
Brief Title
Study to Evaluate Changes in Limb Fat When Switching From a Thymidine Analogue
Acronym
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)
Study Type
Interventional
2. Study Status
Record Verification Date
June 2008
Overall Recruitment Status
Completed
Study Start Date
February 2003 (undefined)
Primary Completion Date
October 2004 (Actual)
Study Completion Date
February 2006 (Actual)
3. Sponsor/Collaborators
Name of the Sponsor
Gilead Sciences
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief 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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lipodystrophy
Keywords
lipodystrophy
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
100 (Actual)
8. Arms, Groups, and Interventions
Arm Title
A
Arm Type
Experimental
Arm Description
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
Arm Title
B
Arm Type
Active Comparator
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
tenofovir DF
Intervention Description
tenofovir DF 300mg once daily along with the other antiviral drugs
Intervention Type
Drug
Intervention Name(s)
abacavir 300mg twice daily
Intervention Description
abacavir 300mg twice daily along with the other antiviral drugs
Primary Outcome Measure Information:
Title
Change in total limb fat mass by DEXA scan
Time Frame
24 and 48 weeks
Secondary Outcome Measure Information:
Title
Change in VAT by single slice L4 abdominal CT scan
Time Frame
24 and 48 weeks
Title
Change in viral load measurements and CD4 cell count
Time Frame
24 and 48 Weeks
Title
Change in fasting cholesterol and triglycerides
Time Frame
24 and 48 Weeks
Title
Change in blood insulin and fasting glucose
Time Frame
24 and 48 Weeks
Title
Change in blood lactate and anion gap
Time Frame
24 and 48 Weeks
Title
Change in bone mineral density by DEXA scan
Time Frame
24 and 48 Weeks
Title
Incidence of adverse events
Time Frame
Upto 48 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Geoff Cotton
Organizational Affiliation
Gilead Sciences
Official's Role
Study Director
Facility Information:
Facility Name
Gilead Sciences
City
Abingdon
State/Province
Cambridge
ZIP/Postal Code
CB1 6GT
Country
United Kingdom
12. IPD Sharing Statement
Links:
URL
http://www.gileadclinicaltrials.com/
Description
Study results
Learn more about this trial
Study to Evaluate Changes in Limb Fat When Switching From a Thymidine Analogue
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