A Study of the Neurological Effects of Adding Maraviroc to HAART Regimen in Patients With HIV (HANDmac) (HANDmac)

This study has been completed.
Sponsor:
Collaborator:
ViiV Healthcare
Information provided by (Responsible Party):
Bruce Brew, St Vincent's Hospital
ClinicalTrials.gov Identifier:
NCT01449006
First received: October 6, 2011
Last updated: April 13, 2016
Last verified: April 2016
  Purpose

HIV related cognitive impairment still occurs despite highly active antiretroviral therapy (HAART). HIV disease affects the brain in 20-40% of patients with advancing HIV disease; leading to varying degrees of cognitive impairment, recently termed HIV associated neurocognitive disorders (HAND). HAND may occur in patients who are virally suppressed in both blood and CSF.

Patients with HIV Associated Neurocognitive Disorders (HAND) who are virally suppressed in both their blood and cerebrospinal fluid (CSF), whilst on a highly active antiretroviral therapy (HAART) regimen may have significant cognitive improvement with HAART intensification with the medication Maraviroc; compared to those who remain on their existing regimen.

This study will be a prospective, interventional, randomised and unblinded controlled clinical trial. The aim of this study will be to determine whether HAART intensification with the medication Maraviroc, leads to significant improvement in HIV associated neurocognitive disorders (HAND).

Patients with the recent progression (within 6 months) of HAND (validated by neuropsychological assessment) on HAART, who are virally suppressed (<50 copies per ml) in blood and CSF will be randomised to have their existing HAART regimen intensified with Maraviroc, or not. The control arm will remain on their medication regimen as prescribed. The target is to enrol 70 patients into the control group, and 70 patients into the Maraviroc intensification group.

Patients will undergo baseline neuropsychological testing, MRI, blood tests, and cerebrospinal fluid (CSF) tests (via a lumbar puncture). The methods used to determine the effectiveness of adding Maraviroc, will include further neuropsychological assessment at 6 months, and neuropsychological assessment, MRI and CSF assessment again at 12 months.

Neuropsychological testing completed at 6 and 12 months will be completed by a "blind assessor", in that they will have no knowledge of which arm (treatment or control) the participant is enrolled in.

An evaluation (neuropsychological testing) will be performed should the patient deteriorate during the course of the study, as recognised by the patient's managing physician.

At the end of the study protocol (12 months) the patient's HAART therapy will be managed by their primary physician.


Condition Intervention Phase
Human Immunodeficiency Virus (HIV)
HIV Associated Neurocognitive Disorders (HAND)
Drug: Maraviroc
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomised Controlled Clinical Trial of the Efficacy of HAART Intensification With Maraviroc in HIV Virally Suppressed Patients With Cognitive Impairment

Resource links provided by NLM:


Further study details as provided by St Vincent's Hospital, Sydney:

Primary Outcome Measures:
  • Change in Neurocognitive Functioning [ Time Frame: Baseline, 6-months and 12-months ] [ Designated as safety issue: No ]
    Change in overall neurocognitive performance, defined as a global neurocognitive z-score, over the study time-period (baseline, 6-months, 12-months). To derive this score, 1) raw scores obtained from a 5-domain brief neurocognitive battery were converted to age-corrected z-scores (M=0, SD=1) and 2) the set of individual subtest z-scores were averaged to generate a single composite (global) z-score for each subject. Lower (negative) scores therefore indicate greater levels of cognitive impairment.


Secondary Outcome Measures:
  • Change in CSF Neopterin Concentration [ Time Frame: Baseline and 12-months ] [ Designated as safety issue: No ]
    Change in concentration of the CSF neuroinflammatory marker neopterin (measured in nmol/L) from baseline to 12-months.

  • Change in MRS Cerebral Metabolite Ratios in Basal Ganglia [ Time Frame: Baseline and 12 months ] [ Designated as safety issue: No ]
    Change in major cerebral metabolites in the basal ganglia, as measured by 1H-Magnetic Resonance Spectroscopy (MRS), between baseline and 12-months. Spectra were acquired on a Phillips Achieva 3T MRI scanner using point-resolved spectroscopy (PRESS) sequence with short echot time (TE). jMRUI/AMARES algorithm was used to process spectra. Metabolite ratios were calculated for the following metabolites: N-acetyl aspartate (NAA), choline (Cho), creatine (Cr), myo-inositol (mIo), in relation to internal water (H20) as standard.

  • Change in MRS Cerebral Metabolite Ratios in Frontal White Matter [ Time Frame: Baseline and 12 months ] [ Designated as safety issue: No ]
    Change in major cerebral metabolites in the frontal white matter, as measured by 1H-Magnetic Resonance Spectroscopy (MRS), between baseline and 12-months. Spectra were acquired on a Phillips Achieva 3T MRI scanner using point-resolved spectroscopy (PRESS) sequence with short TE. jMRUI/AMARES algorithm was used to process spectra. Metabolite ratios were calculated for the following metabolites: N-acetyl aspartate (NAA), choline (Cho), creatine (Cr), myo-inositol (mIo), glutamate/glutamine complex (Glx), in relation to internal H2O as standard.


Enrollment: 19
Study Start Date: October 2011
Study Completion Date: September 2014
Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
No Intervention: Standard of care HAART regimen
Participants randomised to this arm of the trial will remain on their usual prescribed HAART regimen.
Experimental: Maraviroc
Participants randomised to this arm will remain on their usual prescribed HAART regimen, with the addition of Maraviroc. Maraviroc will be prescribed according to the Product Information Sheet, with consideration given to background therapy.
Drug: Maraviroc
Maraviroc oral tablet. Dosage: 150 mg twice daily, 300 mg twice daily, or 600 mg twice daily. Dosing will be dependent on the participant's background HAART therapy, and will be in accordance with the product information sheet.
Other Name: Celsentri

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • HIV Positive
  • On HAART, with plasma viral load < 50 copies/ml for previous 12 months or more
  • Able to provide informed consent
  • HAND diagnosis, with symptom progression within previous 6 months

Exclusion Criteria:

  • Non-HIV related neurological disorders and active central nervous system (CNS) opportunistic infection (as assessed by full blood count, electrolytes, creatinine, glucose, liver funciton tests, cryptococcal antigen, venereal disease research laboratory (VDRL), MRI brain scan and CSF analysis for cell count, protein, glucose, culture, VDRL and cryptococcal antigen)
  • Psychiatric disorders on the psychiatric axis
  • Current major depression
  • Current substance use disorder, or severe substance use disorder within 12 months of study entry
  • Active Hepatitis C Virus (HCV) (detectable HCV RNA)
  • History of loss of consciousness > 1 hour
  • Non-proficient in English
  • Medications known to pharmacologically interact with antiretrovirals (ARVs)
  • Currently taking an entry inhibitor
  • Pregnancy (as assessed by the urine pregnancy test)
  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: NCT01449006

Locations
Australia, New South Wales
St. Vincent's Hospital
Sydney, New South Wales, Australia, 2010
Australia, Victoria
The Alfred Hospital
Melbourne, Victoria, Australia, 3181
Sponsors and Collaborators
Bruce Brew
ViiV Healthcare
Investigators
Principal Investigator: Bruce J Brew, MBBS, PhD St Vincent's Hospital, Sydney, Australia
  More Information

Publications:
Responsible Party: Bruce Brew, Professor, St Vincent's Hospital
ClinicalTrials.gov Identifier: NCT01449006     History of Changes
Other Study ID Numbers: 11/066  114560 
Study First Received: October 6, 2011
Results First Received: February 9, 2016
Last Updated: April 13, 2016
Health Authority: Australia: Human Research Ethics Committee
Australia: Department of Health and Ageing Therapeutic Goods Administration

Keywords provided by St Vincent's Hospital, Sydney:
HIV
HAND
Maraviroc
Neurocognitive
Neurology
Human Immunodeficiency Virus
HIV Associated Neurocognitive Disorders

Additional relevant MeSH terms:
Immunologic Deficiency Syndromes
Acquired Immunodeficiency Syndrome
HIV Infections
Neurocognitive Disorders
Immune System Diseases
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Slow Virus Diseases
Mental Disorders
Maraviroc
CCR5 Receptor Antagonists
Molecular Mechanisms of Pharmacological Action
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents

ClinicalTrials.gov processed this record on August 25, 2016