Maraviroc Abacavir STudy - Effect on Endothelial Recovery

Endothelial Dysfunction Clinical Trial

— MASTER  

Official title:

Maraviroc Abacavir STudy - Effect on Endothelial Recovery

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01389063
• Other study ID #: MASTER2010
• Status: Recruiting
• Phase: Phase 4
• First received: July 5, 2011
• Last updated: December 17, 2013
• Start date: January 2012
• Est. completion date: October 2014

Study information

• Verified date: December 2013
• Source: UMC Utrecht
• Contact: Steven FL van Lelyveld, MD
• Email: s.f.l.vanlelyveld[@]umcutrecht.nl
• Is FDA regulated: No
• Health authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 24
• Est. completion date: October 2014
• Est. primary completion date: September 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Endothelial Dysfunction

Intervention

Drug:
• Maraviroc
HAART of subjects enrolled in arm A will be intensified with maraviroc during week 1-8.

Locations

Country	Name	City	State
Netherlands	University Medical Center Utrecht	Utrecht

Sponsors (1)

Lead Sponsor	Collaborator
S.F.L. van Lelyveld

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in flow-mediated dilatation (FMD) of the brachial artery after 8 weeks of maraviroc treatment as compared to the control group		After 8 weeks of treatment (cross-over)	No
Secondary	Change in markers of chronic inflammation		Baseline, week 2, week 4, week 8, week 10, week 12 and week 16	No
Secondary	Change in markers of immune activation		Baseline, week 2, week 4, week 8, week 10, week 12 and week 16	No
Secondary	Change in markers of endothelial function		Baseline, week 2, week 4, week 8, week 10, week 12 and week 16	No
Secondary	Changes in plasma HIV-RNA below 50 copies/ml		Baseline, week 8, week 16	No
Secondary	Change in endothelial function measured by EndoPAT		baseline, week 8, week 16	No