MARCH Central Nervous System Substudy - Full Text View

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:

Neurocognitive function as assessed by a computerised testing battery called CogState;
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
Study Completion Date:	December 2015
Primary Completion Date:	December 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 (Adult, Senior)
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
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


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:	January 18, 2016
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:


Ritonavir Lopinavir Atazanavir Sulfate Darunavir HIV Protease Inhibitors Fosamprenavir Tenofovir Zidovudine Emtricitabine Lamivudine 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

ClinicalTrials.gov processed this record on September 23, 2016