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MARCH Central Nervous System Substudy

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ClinicalTrials.gov Identifier: NCT01637233
Recruitment Status : Completed
First Posted : July 11, 2012
Last Update Posted : January 20, 2016
Sponsor:
Information provided by (Responsible Party):
Kirby Institute

Study Description
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Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information
Brief Summary:

This substudy is a prospective, observational, open-label, randomised study within the MARCH study. The purpose of this substudy is to investigate the changes in cerebral function parameters at 5 timepoints over 96 weeks of the three different treatment arms within the MARCH study. The investigators hypothesise that there will be improvements in cerebral function in those patients randomised, as part of the parent study, into the maraviroc arms.

the assessments in this CNS substudy will include:

  1. Neurocognitive function as assessed by a computerised testing battery called CogState;
  2. changes in cerebral metabolites as measured via 1H Magnetic Resonance Spectroscopy (1H-MRS)

In those randomised to the maraviroc arms (arms 2 and 3) there is an optional Lumbar puncture at week 48. The cerebrospinal fluid will be used to measure maraviroc levels and an ultrasensitive CSF HIV-1 viral load. These results will be matched with levels in the plasma.


Condition or disease Intervention/treatment
HIV-1 Infection Drug: Arm 1 TNucleotide Analogue Reverse Transcriptase Inhibitors and Boosted Protease Inhibitors Drug: Arm 2 Maraviroc and Protease Inhibitors Drug: Arm 3 Maraviroc and Nucleotide Analogue Reverse Transcriptase Inhibitors

Detailed Description:
this is detailed above, this is a substudy of MARCH

Study Design
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Study Type : Observational
Actual Enrollment : 28 participants
Time Perspective: Prospective
Official Title: Maraviroc Switch Central Nervous System (CNS) Substudy: a Substudy of MARCH, a Randomised, Open-label Study to Evaluate the Efficacy and Safety of Maraviroc (MVC) as a Switch for Either Nucleoside or Nucleotide Analogue Reverse Transcriptase Inhibitors (N(t)RTI) or Boosted Protease Inhibitors (PI/r) in HIV-1 Infected Individuals With Stable, Well-controlled Plasma HIV-RNA While Taking Their First N(t)RTI + PI/r Regimen of Combination Antiretroviral Therapy (cART).
Study Start Date : June 2012
Actual Primary Completion Date : December 2015
Actual Study Completion Date : December 2015

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS
Drug Information available for: Maraviroc
U.S. FDA Resources

Groups and Cohorts
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Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Group/Cohort Intervention/treatment
NRTI + PI
This is the randomisation of the main study, Arm 1
 Drug: Arm 1 TNucleotide Analogue Reverse Transcriptase Inhibitors and Boosted Protease Inhibitors
NRTI+PI
Other Names:
  • tenofovir
  • emtricitabine
  • zidovudine
  • lamivudine
  • abacavir
  • Ritonavir
  • lopinavir
  • darunavir
  • atazanavir
  • fosamprenavir
maraviroc + PI
this is the randomisation of the main study, Arm 2
 Drug: Arm 2 Maraviroc and Protease Inhibitors
maraviroc + PI
Other Names:
  • maraviroc
  • Ritonavir
  • lopinavir
  • darunavir
  • atazanavir
  • fosamprenavir
maraviroc + NRTI
this is the randomisation of the main study, Arm 3
 Drug: Arm 3 Maraviroc and Nucleotide Analogue Reverse Transcriptase Inhibitors
maraviroc + NRTI
Other Names:
  • maraviroc
  • tenofovir
  • emtricitabine
  • zidovudine
  • lamivudine
  • abacavir


Outcome Measures
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Primary Outcome Measures :
  1. To assess changes in NC function over 96 weeks, measured via a computerised testing battery in HIV-infected subjects stable on antiretroviral therapy randomised to three different treatment approaches [ Time Frame: 96 weeks ]
    using CogState testing at 5 timepoints, weeks 0, 12, 24, 48, 96

  2. To assess changes in cerebral metabolites over 96 weeks, measured via 1H Magnetic Resonance Spectroscopy (1H-MRS), in HIV-infected subjects stable on antiretroviral therapy randomised to three different treatment approaches [ Time Frame: 96 weeks ]

    Assessment of CNS metabolites via 1H-MRS at week 0, 48, 96

    • Cerebral metabolites in frontal white and grey voxels, and basal ganglia will be measured
    • Measurable metabolites will include assessment of neuronal markers, N-acetyl-aspartate, and inflammatory markers, myo-Inositols and Choline


Secondary Outcome Measures :
  1. to assess CSF HIV-1 RNA and CSF maraviroc concentration (in the MVC treatment arms) versus plasma HIV -1 RNA and MVC concentration after 48 weeks of therapy [ Time Frame: 48 weeks ]

    A LP examination at week 48 (optional and only in the MVC treatment arms, and only if there is no contraindication to LP) to assess, with matched plasma samples:

    • CSF MVC concentration
    • CSF HIV-1 RNA
    • CSF biomarkers


Biospecimen Retention:   Samples Without DNA
plasma and CSF

Eligibility Criteria
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Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population
participants in the MARCH main study who are eligible for the CNS substudy and provide written informed consent for participation
Criteria

Inclusion Criteria:

  • Provision of written, informed consent for participation in the substudy
  • Enrolled into the substudy either at or before the week 0 visit of the main study

Exclusion Criteria:

  • Pre-existing CNS diseases
  • Recent head injury (past three months)
  • Current history of major depression or psychosis
Contacts and Locations
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Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01637233


Locations
Argentina
Hospital Ramos Mejía
Buenos Aires, Argentina, C1221ADC
Fundación IDEAA
Buenos Aires, Argentina, C1405CKC
CAICI
Rosario, Argentina
Thailand
Chulalongkorn University Hospital
Bangkok, Thailand, 10330
United Kingdom
Brighton & Sussex University NHS Trust
Brighton, Sussex, United Kingdom, BN21ES,
Imperial Healthcare, St. Mary's Hospital
London, United Kingdom, W2
Sponsors and Collaborators
Kirby Institute
Investigators
Principal Investigator: Alan Winston, MD Imperial Healthcare, London, UK
More Information
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Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Responsible Party: Kirby Institute
ClinicalTrials.gov Identifier: NCT01637233     History of Changes
Other Study ID Numbers: MARCH-Kirby CNS
2011-002107-15 ( EudraCT Number )
First Posted: July 11, 2012    Key Record Dates
Last Update Posted: January 20, 2016
Last Verified: January 2016

Keywords provided by Kirby Institute:
HIV-1 infection
neurocognitive function
switch study

Additional relevant MeSH terms:
Ritonavir
Lopinavir
Darunavir
Atazanavir Sulfate
HIV Protease Inhibitors
Fosamprenavir
Tenofovir
Lamivudine
Emtricitabine
Zidovudine
Maraviroc
Abacavir
Protease Inhibitors
 Reverse Transcriptase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Cytochrome P-450 CYP3A Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Nucleic Acid Synthesis Inhibitors
Antimetabolites
CCR5 Receptor Antagonists