- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01449006
A Study of the Neurological Effects of Adding Maraviroc to HAART Regimen in Patients With HIV (HANDmac) (HANDmac)
A Randomised Controlled Clinical Trial of the Efficacy of HAART Intensification With Maraviroc in HIV Virally Suppressed Patients With Cognitive Impairment
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.
Study Overview
Status
Intervention / Treatment
Study Type
Enrollment (Actual)
Phase
- Phase 4
Contacts and Locations
Study Locations
-
-
New South Wales
-
Sydney, New South Wales, Australia, 2010
- St. Vincent's Hospital
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Victoria
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Melbourne, Victoria, Australia, 3181
- The Alfred Hospital
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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)
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
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.
|
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 Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in Neurocognitive Functioning
Time Frame: Baseline, 6-months and 12-months
|
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.
|
Baseline, 6-months and 12-months
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in CSF Neopterin Concentration
Time Frame: Baseline and 12-months
|
Change in concentration of the CSF neuroinflammatory marker neopterin (measured in nmol/L) from baseline to 12-months.
|
Baseline and 12-months
|
Change in MRS Cerebral Metabolite Ratios in Basal Ganglia
Time Frame: Baseline and 12 months
|
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.
|
Baseline and 12 months
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Change in MRS Cerebral Metabolite Ratios in Frontal White Matter
Time Frame: Baseline and 12 months
|
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.
|
Baseline and 12 months
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Bruce J Brew, MBBS, PhD, St Vincent's Hospital - Sydney, Australia
Publications and helpful links
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Mental Disorders
- RNA Virus Infections
- Virus Diseases
- Infections
- Blood-Borne Infections
- Communicable Diseases
- Sexually Transmitted Diseases, Viral
- Sexually Transmitted Diseases
- Lentivirus Infections
- Retroviridae Infections
- Immune System Diseases
- Slow Virus Diseases
- HIV Infections
- Acquired Immunodeficiency Syndrome
- Immunologic Deficiency Syndromes
- Neurocognitive Disorders
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Antiviral Agents
- Anti-HIV Agents
- Anti-Retroviral Agents
- HIV Fusion Inhibitors
- Viral Fusion Protein Inhibitors
- CCR5 Receptor Antagonists
- Maraviroc
Other Study ID Numbers
- 11/066
- 114560 (Other Grant/Funding Number: VIIV Healthcare Australia)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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