HIV infected patients treated with abacavir might have a higher risk for the occurrence of cardiovascular events. At time of writing of this protocol the underlying mechanism is not yet elucidated, however some studies find impaired endothelial function and elevated markers of chronic inflammation in these patients,suggesting a higher lever of chronic inflammation. Recently maraviroc...
Brief Summary
Official Title: “Maraviroc Abacavir STudy - Effect on Endothelial Recovery”
HIV infected patients treated with abacavir might have a higher risk for the occurrence of cardiovascular events. At time of writing of this protocol the underlying mechanism is not yet elucidated, however some studies find impaired endothelial function and elevated markers of chronic inflammation in these patients,suggesting a higher lever of chronic inflammation.
Recently maraviroc (Celsentri®), a CCR5-receptor antagonist, became available for treatment of patients infected with HIV-1.
Improvement of endothelial function may be a potential beneficial side effect of treatment with maraviroc, due to the potential reduction of immune activation and chronic inflammation as a result of blocking the CCR5-coreceptor. Moreover, treatment intensification of HAART with maraviroc in patients with suppressed plasma HIV_RNA may decrease plasma HIVRNA below the cut-off of 50 copies/ml as well.
The investigators hypothesize that maraviroc intensification therapy in patients on an abacavir-containing regimen will improve endothelial function.
The objectives of this study are: First, to assess the effect of addition of maraviroc to an abacavir-containing regimen on endothelial function; second, to assess the effect of this intervention on markers of immune activation and chronic inflammation, and on plasma HIV-RNA below 50 copies/ml.
Detailed Clinical Trial Description
The MASTER study is a phase IV, randomized, open label, cross-over, intervention study.
Study subjects who are on stable abacavir-containing regimen will be randomized into two arms. In arm A maraviroc will be added to their regimen at baseline, while study subjects in arm B will continue their abacavir-containing regimen. After 8 weeks, cross-over of the study arms will be performed. Subjects in arm A will then stop maraviroc, while in subjects in arm B maraviroc will be added to their regimen (for 8 weeks again). The total duration of the study will be 16 weeks.
Intervention(s) in this Clinical Trial
Drug: Maraviroc
HAART of subjects enrolled in arm A will be intensified with maraviroc during week 1-8.
Arms, Groups and Cohorts in this Clinical Trial
Active Comparator: Arm A
HAART of subjects in arm A will be intensified with maraviroc during week 1-8.
Active Comparator: Arm B
HAART of subjects enrolled in arm B will be intensified with maraviroc during week 9-16
Outcome Measures for this Clinical Trial
Primary Measures
Change in flow-mediated dilatation (FMD) of the brachial artery after 8 weeks of maraviroc treatment as compared to the control group
Time Frame: After 8 weeks of treatment (cross-over)
Safety Issue?: No
Secondary Measures
Change in markers of chronic inflammation
Time Frame: Baseline, week 2 (A) or 10 (B), week 4 (A) or 12 (B), week 8, week 16
Safety Issue?: No
Change in markers of immune activation
Time Frame: Baseline, week 2 (A) or 10 (B), week 4 (A) or 12 (B), week 8, week 16
Safety Issue?: No
Change in markers of endothelial function
Time Frame: Baseline, week 2 (A) or 10 (B), week 4 (A) or 12 (B), week 8, week 16
Safety Issue?: No
Changes in plasma HIV-RNA below 50 copies/ml
Time Frame: Baseline, week 8, week 16
Safety Issue?: No
Change in endothelial function measured by EndoPAT
Time Frame: baseline, week 8, week 16
Safety Issue?: No
Criteria for Participation in this Clinical Trial
Inclusion Criteria:
Age > 18 years
HIV-1 infection
Treatment with antiretroviral regimen containing abacavir for at least the previous 3 months
Undetectable plasma HIV RNA (50 cp/ml) for at least 6 months (one 'blip' allowed, which is defined as a detectable plasma HIV-RNA level between 50 and 400 copies/ml, preceded and followed by undetectable (<50 copies/ml) plasma HIV-RNA measurements) CD4+ cell count > 200 cells/µL
Signed informed consent
Exclusion Criteria:
Pregnancy
Breastfeeding
Allergy for peanuts or soya
Hypersensitivity for maraviroc
Treatment of underlying malignancy
Acute infection in the preceding 30 days
Renal insufficiency requiring hemodialysis
Acute or decompensated chronic hepatitis
Modification of antiretroviral regimen in the previous 3 months
Gender Eligibility for this Clinical Trial: Both
Minimum Age for this Clinical Trial: 18 Years
Maximum Age for this Clinical Trial: N/A
Are Healthy Volunteers Accepted for this Clinical Trial?: No
Clinical Trial Investigator Information
Lead Investigator: UMC Utrecht Other
Overall Clinical Trial Officials and Contacts
A IM Hoepelman, MD, PhD Principal Investigator UMC Utrecht
Overall Contact: Steven FL van Lelyveld, MD s.f.l.vanlelyveld@umcutrecht.nl
Additional Information
Information obtained from ClinicalTrials.gov on July 06, 2011
Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT01389063
Study ID Number: MASTER2010
ClinicalTrials.gov Identifier: NCT01389063
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
Copyright © 2011 ClinicalTrials
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