NCT00875368

Brief Summary

Rationale: Improving cellular immunity by means of increasing CD4 cells is one of the goals of antiretroviral therapy in HIV, which is achieved by means of virological suppression. A certain group of patients, the so called "immunologic non responders", fail to reach an acceptable CD4 cell increase despite an adequate virologic response on antiretroviral treatment. Recently a new antiretroviral agent, maraviroc (Celsentry®), is registered for the treatment of patients infected with CCR5 tropic HIV-1 virus. However, data is available suggesting that treatment with maraviroc leads to immune recovery (increase in CD4 cells) in patients who are infected with dual/mixed tropic HIV-1 virus, in the absence of a virologic response. This suggests an alternative mechanism for immune recovery, which could be especially beneficial for this group of patients. Hypothesis: Maraviroc, by a yet unknown mechanism, stimulates immune recovery by increasing CD4+ cell count. Objective: The primary objective is to confirm the hypothesis that maraviroc stimulates immune recovery; the secondary objective is to explore, by virologic and immunologic investigations, the underlying mechanisms of this hypothesis. Study design: multicentre, randomized, placebo-controlled, double blind, exploratory mechanistic study. Study population: HIV-1 infected patients 18 years or older, who meet the inclusion criteria. Intervention: One group receives maraviroc (dose dependent on co-medication), the other group placebo. Main study parameters/endpoints: A 30% increase in CD4 cell rise in the treatment group (compared with placebo). Nature and extent of the burden and risks associated with participation, benefit and group relatedness:

  1. 1.In the treatment group subjects will start with a registered antiretroviral agent (maraviroc).
  2. 2.During the treatment year patients will perform several study visits, probably three more compared with regular visits on the outpatient clinic.
  3. 3.Each visit, blood will be drawn by venepuncture for immunologic and virologic investigations (see flow chart).

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
85

participants targeted

Target at P50-P75 for phase_4 hiv-infections

Timeline
Completed

Started Feb 2009

Typical duration for phase_4 hiv-infections

Geographic Reach
1 country

10 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

February 1, 2009

Completed
2 months until next milestone

First Submitted

Initial submission to the registry

April 2, 2009

Completed
1 day until next milestone

First Posted

Study publicly available on registry

April 3, 2009

Completed
2.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 1, 2011

Completed
8 months until next milestone

Study Completion

Last participant's last visit for all outcomes

August 1, 2012

Completed
Last Updated

September 10, 2013

Status Verified

September 1, 2013

Enrollment Period

2.8 years

First QC Date

April 2, 2009

Last Update Submit

September 6, 2013

Conditions

HIV Infections

Keywords

HIV-1HAARTCD4 cellImmunologic non-respondersImmunologytreatment experienced

Outcome Measures

Primary Outcomes (1)

  • 30% increase in CD4+ cell count after 48 weeks

    48 weeks

Study Arms (2)

Maraviroc

ACTIVE COMPARATOR
Drug: maraviroc

Placebo

PLACEBO COMPARATOR

Placebo drug

Drug: Placebo

Interventions

maravirocDRUG

maraviroc dose dependent on co-medication

Also known as: Celsentri, Celsentry
Maraviroc
PlaceboDRUG

Placebo drug

Placebo

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Age 18 years or older
  • HAART with a maximal treatment interruption of two weeks
  • viral suppression (\< 50 copies/ml) for 6 months
  • And either:
  • CD4+ count \< 200 cells/microliter after minimal one year of treatment with HAART (study group one) OR
  • a CD4+ cell count between 200 and 350 cells/microliter after minimal two years of treatment with HAART (study group two)

You may not qualify if:

  • HAART consisting of a combination of tenofovir and didanosine
  • Active infection for which antimicrobial treatment
  • Acute hepatitis B or C
  • Chronic hepatitis B or C for which treatment with (peg)interferon and/or ribavirin (Note: patients with untreated chronic hepatitis B or C can be included)
  • Immunosuppressive medication
  • Radiotherapy or chemotherapy in the past 2 years
  • Pregnancy or breastfeeding an infant
  • Subjects with known hypersensitivity to maraviroc or to peanuts, or any of its excipients or dyes as follows:
  • Excipients from tablet: microcrystalline cellulose, dibasic calcium phosphate (anhydrous), sodium starch glycolate, magnesium stearate.
  • Film-coat: \[Opadry II Blue (85G20583) contains FD\&C blue #2 aluminium lake, soya lecithin, polyethylene glycol (macrogol 3350), polyvinyl alcohol, talc and titanium dioxide.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (10)

Onze Lieve Vrouwe Gasthuis

Amsterdam, 1091 AC, Netherlands

Location

Academisch Medisch Centrum (AMC)

Amsterdam, 1105AZ, Netherlands

Location

Slotervaartziekenhuis

Amsterdam, Netherlands

Location

Rijnstate Hospital

Arnhem, Netherlands

Location

Kennemer Gasthuis

Haarlem, Netherlands

Location

Leids Universitair Medisch Centrum (LUMC)

Leiden, Netherlands

Location

Erasmus MC

Rotterdam, 3015GJ, Netherlands

Location

Maasstad Ziekenhuis

Rotterdam, Netherlands

Location

Sint Elisabeth Ziekenhuis

Tilburg, Netherlands

Location

Ùniversity Medical Center Utrecht

Utrecht, 3584CX, Netherlands

Location

Related Publications (1)

  • van Lelyveld SF, Drylewicz J, Krikke M, Veel EM, Otto SA, Richter C, Soetekouw R, Prins JM, Brinkman K, Mulder JW, Kroon F, Middel A, Symons J, Wensing AM, Nijhuis M, Borghans JA, Tesselaar K, Hoepelman AI; MIRS study group. Maraviroc Intensification of cART in Patients with Suboptimal Immunological Recovery: A 48-Week, Placebo-Controlled Randomized Trial. PLoS One. 2015 Jul 24;10(7):e0132430. doi: 10.1371/journal.pone.0132430. eCollection 2015.

    PMID: 26208341DERIVED

MeSH Terms

Conditions

HIV Infections

Interventions

Maraviroc

Condition Hierarchy (Ancestors)

Blood-Borne InfectionsCommunicable DiseasesInfectionsSexually Transmitted Diseases, ViralSexually Transmitted DiseasesLentivirus InfectionsRetroviridae InfectionsRNA Virus InfectionsVirus DiseasesGenital DiseasesUrogenital DiseasesImmunologic Deficiency SyndromesImmune System Diseases

Intervention Hierarchy (Ancestors)

CyclohexanesCycloparaffinsHydrocarbons, AlicyclicHydrocarbons, CyclicHydrocarbonsOrganic ChemicalsTriazolesAzolesHeterocyclic Compounds, 1-RingHeterocyclic Compounds

Study Officials

  • Andy IM Hoepelman, MD, PhD

    UMC Utrecht

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 4
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR INVESTIGATOR
PI Title
Coordinating investigator

Study Record Dates

First Submitted

April 2, 2009

First Posted

April 3, 2009

Study Start

February 1, 2009

Primary Completion

December 1, 2011

Study Completion

August 1, 2012

Last Updated

September 10, 2013

Record last verified: 2013-09

Locations

NL(10)