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MARCH Central Nervous System Substudy

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Kirby Institute
ClinicalTrials.gov Identifier:
NCT01637233
First received: June 27, 2012
Last updated: July 17, 2014
Last verified: July 2014
  Purpose

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 Intervention
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

Study Type: Observational
Study Design: 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).

Resource links provided by NLM:


Further study details as provided by Kirby Institute:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    using CogState testing at 5 timepoints, weeks 0, 12, 24, 48, 96

  • 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 ] [ Designated as safety issue: No ]

    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:
  • 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 ] [ Designated as safety issue: Yes ]

    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


Enrollment: 28
Study Start Date: June 2012
Estimated Study Completion Date: January 2016
Estimated Primary Completion Date: January 2015 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
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

Detailed Description:

this is detailed above, this is a substudy of MARCH

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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
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: NCT01637233

Locations
Argentina
Fundación IDEAA
Buenos Aires, Argentina, C1405CKC
Hospital Ramos Mejía
Buenos Aires, Argentina, C1221ADC
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

No publications provided

Responsible Party: Kirby Institute
ClinicalTrials.gov Identifier: NCT01637233     History of Changes
Other Study ID Numbers: MARCH-Kirby CNS, 2011-002107-15
Study First Received: June 27, 2012
Last Updated: July 17, 2014
Health Authority: Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica
Australia: Department of Health and Ageing Therapeutic Goods Administration
Thailand: Ministry of Public Health
United Kingdom: Medicines and Healthcare Products Regulatory Agency

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

Additional relevant MeSH terms:
Infection
Abacavir
Atazanavir
Darunavir
Emtricitabine
Fosamprenavir
HIV Protease Inhibitors
Lamivudine
Lopinavir
Protease Inhibitors
Reverse Transcriptase Inhibitors
Ritonavir
Tenofovir
Zidovudine
Anti-HIV Agents
Anti-Infective Agents
Anti-Retroviral Agents
Antimetabolites
Antiviral Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on November 24, 2014