Maraviroc Abacavir STudy - Effect on Endothelial Recovery

NCT01389063 | Unknown Phase 4

• 1 other identifier: MASTER2010
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Endothelial Dysfunction

Keywords

endothelial function; CCR5 receptor; Maraviroc; Abacavir; Flow Mediated Dilatation; EndoPAT

Outcome Measures

Primary Outcomes (1)

• 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)

Secondary Outcomes (5)

• Change in markers of chronic inflammation

  Baseline, week 2, week 4, week 8, week 10, week 12 and week 16

• Change in markers of immune activation

  Baseline, week 2, week 4, week 8, week 10, week 12 and week 16

• Change in markers of endothelial function

  Baseline, week 2, week 4, week 8, week 10, week 12 and week 16

• Changes in plasma HIV-RNA below 50 copies/ml

  Baseline, week 8, week 16

• Change in endothelial function measured by EndoPAT

  baseline, week 8, week 16

Study Arms (2)

Arm A

ACTIVE COMPARATOR

HAART of subjects in arm A will be intensified with maraviroc during week 1-8.

Drug: Maraviroc

Arm B

ACTIVE COMPARATOR

HAART of subjects enrolled in arm B will be intensified with maraviroc during week 9-16

Drug: Maraviroc

Interventions

Maraviroc DRUG

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

Also known as: Celsentri

Arm A; Arm B

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• S.F.L. van Lelyveld: lead

Study Sites (1)

University Medical Center Utrecht

Utrecht, 3584CX, Netherlands

RECRUITING

Related Publications (1)

• Krikke M, Tesselaar K, Arends JE, Drylewicz J, Otto SA, van Lelyveld SF, Visseren FJ, Hoepelman AI. Maraviroc Intensification Improves Endothelial Function in Abacavir-Treated Patients, an Open-Label Randomized Cross-Over Pilot Study. Infect Dis Ther. 2016 Sep;5(3):389-404. doi: 10.1007/s40121-016-0115-0. Epub 2016 Jun 14.

  PMID: 27300170 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Insulin-Dependent, 22

Interventions

Maraviroc

Intervention Hierarchy (Ancestors)

Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• A IM Hoepelman, MD, PhD

  UMC Utrecht

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Steven FL van Lelyveld, MD

CONTACT

s.f.l.vanlelyveld@umcutrecht.nl

A IM Hoepelman, MD, PhD

CONTACT

i.m.hoepelman@umcutrecht.nl

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Coordinating investigator

Study Record Dates

• First Submitted: July 5, 2011
• First Posted: July 7, 2011
• Study Start: January 1, 2012
• Primary Completion: September 1, 2014
• Study Completion: October 1, 2014
• Last Updated: December 18, 2013

Record last verified: 2013-12

Locations

NL (1)