Maraviroc Abacavir STudy - Effect on Endothelial Recovery (MASTER)

This study is currently recruiting participants. (see Contacts and Locations)
Verified December 2013 by UMC Utrecht
Sponsor:
Information provided by (Responsible Party):
S.F.L. van Lelyveld, UMC Utrecht
ClinicalTrials.gov Identifier:
NCT01389063
First received: July 5, 2011
Last updated: December 17, 2013
Last verified: December 2013
  Purpose

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.


Condition Intervention Phase
Endothelial Dysfunction
Drug: Maraviroc
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Maraviroc Abacavir STudy - Effect on Endothelial Recovery

Resource links provided by NLM:


Further study details as provided by UMC Utrecht:

Primary Outcome 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) ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Change in markers of chronic inflammation [ Time Frame: Baseline, week 2, week 4, week 8, week 10, week 12 and week 16 ] [ Designated as safety issue: No ]
  • Change in markers of immune activation [ Time Frame: Baseline, week 2, week 4, week 8, week 10, week 12 and week 16 ] [ Designated as safety issue: No ]
  • Change in markers of endothelial function [ Time Frame: Baseline, week 2, week 4, week 8, week 10, week 12 and week 16 ] [ Designated as safety issue: No ]
  • Changes in plasma HIV-RNA below 50 copies/ml [ Time Frame: Baseline, week 8, week 16 ] [ Designated as safety issue: No ]
  • Change in endothelial function measured by EndoPAT [ Time Frame: baseline, week 8, week 16 ] [ Designated as safety issue: No ]

Estimated Enrollment: 24
Study Start Date: January 2012
Estimated Study Completion Date: October 2014
Estimated Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Arm A
HAART of subjects in arm A will be intensified with maraviroc during week 1-8.
Drug: Maraviroc
HAART of subjects enrolled in arm A will be intensified with maraviroc during week 1-8.
Other Name: Celsentri
Active Comparator: Arm B
HAART of subjects enrolled in arm B will be intensified with maraviroc during week 9-16
Drug: Maraviroc
HAART of subjects enrolled in arm A will be intensified with maraviroc during week 1-8.
Other Name: Celsentri

Detailed 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.

  Eligibility

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

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
  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: NCT01389063

Contacts
Contact: Steven FL van Lelyveld, MD s.f.l.vanlelyveld@umcutrecht.nl
Contact: A IM Hoepelman, MD, PhD i.m.hoepelman@umcutrecht.nl

Locations
Netherlands
University Medical Center Utrecht Recruiting
Utrecht, Netherlands, 3584CX
Contact: Steven FL van Lelyveld, MD       s.f.l.vanlelyveld@umcutrecht.nl   
Sponsors and Collaborators
S.F.L. van Lelyveld
Investigators
Principal Investigator: A IM Hoepelman, MD, PhD UMC Utrecht
  More Information

No publications provided

Responsible Party: S.F.L. van Lelyveld, Coordinating investigator, UMC Utrecht
ClinicalTrials.gov Identifier: NCT01389063     History of Changes
Other Study ID Numbers: MASTER2010
Study First Received: July 5, 2011
Last Updated: December 17, 2013
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by UMC Utrecht:
endothelial function
CCR5 receptor
Maraviroc
Abacavir
Flow Mediated Dilatation
EndoPAT

Additional relevant MeSH terms:
Abacavir
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 22, 2014