MARCH Central Nervous System Substudy

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).

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.

Study Overview

• Status: Completed
• Conditions: HIV-1 Infection
• Intervention / Treatment: 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 Type: Observational
• Enrollment (Actual): 28

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1405CKC
    • Fundacion IDEAA
  • Buenos Aires, Argentina, C1221ADC
    • Hospital Ramos Mejia
  • Rosario, Argentina
    • CAICI
• Thailand
  • Bangkok, Thailand, 10330
    • Chulalongkorn University Hospital
• United Kingdom
  • London, United Kingdom, W2
    • Imperial Healthcare, St. Mary's Hospital
  • Sussex
    • Brighton, Sussex, United Kingdom, BN21ES,
      • Brighton & Sussex University NHS Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• 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

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

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: lamivudine; fosamprenavir; emtricitabine; lopinavir; Ritonavir; zidovudine; abacavir; tenofovir; atazanavir; darunavir
maraviroc + PI; this is the randomisation of the main study, Arm 2	Drug: Arm 2 Maraviroc and Protease Inhibitors; maraviroc + PI; Other Names: maraviroc; fosamprenavir; lopinavir; Ritonavir; atazanavir; darunavir
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: lamivudine; maraviroc; emtricitabine; zidovudine; abacavir; tenofovir

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	using CogState testing at 5 timepoints, weeks 0, 12, 24, 48, 96	96 weeks
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	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	96 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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	48 weeks

Collaborators and Investigators

• Sponsor: Kirby Institute
• Investigators: Principal Investigator: Alan Winston, MD, Imperial Healthcare, London, UK

Study record dates

Study Major Dates

• Study Start: June 1, 2012
• Primary Completion (Actual): December 1, 2015
• Study Completion (Actual): December 1, 2015

Study Registration Dates

• First Submitted: June 27, 2012
• First Submitted That Met QC Criteria: July 10, 2012
• First Posted (Estimate): July 11, 2012

Study Record Updates

• Last Update Posted (Estimate): January 20, 2016
• Last Update Submitted That Met QC Criteria: January 18, 2016
• Last Verified: January 1, 2016

More Information

Terms related to this study

• Keywords: HIV-1 infection; switch study; neurocognitive function
• Additional Relevant MeSH Terms: Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Antimetabolites; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Viral Protease Inhibitors; HIV Fusion Inhibitors; Viral Fusion Protein Inhibitors; CCR5 Receptor Antagonists; Tenofovir; Emtricitabine; Ritonavir; Lopinavir; Lamivudine; Zidovudine; Protease Inhibitors; Maraviroc; Reverse Transcriptase Inhibitors; Darunavir; Atazanavir Sulfate; Abacavir; Dideoxynucleosides; Fosamprenavir; HIV Protease Inhibitors
• Other Study ID Numbers: MARCH-Kirby CNS; 2011-002107-15 (EudraCT Number)