A Randomised Controlled Clinical Trial of the Efficacy of HAART Intensification With Maraviroc in HIV Virally Suppressed Patients With Cognitive Impairment

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

Sponsors

Lead sponsor: Bruce Brew

Collaborator: ViiV Healthcare

Source St Vincent's Hospital, Sydney
Brief Summary

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.

Overall Status Completed
Start Date October 2011
Completion Date September 2014
Primary Completion Date September 2014
Phase Phase 4
Study Type Interventional
Primary Outcome
Measure Time Frame
Change in Neurocognitive Functioning Baseline, 6-months and 12-months
Secondary Outcome
Measure Time Frame
Change in CSF Neopterin Concentration Baseline and 12-months
Change in MRS Cerebral Metabolite Ratios in Basal Ganglia Baseline and 12 months
Change in MRS Cerebral Metabolite Ratios in Frontal White Matter Baseline and 12 months
Enrollment 19
Condition
Intervention

Intervention type: Drug

Intervention name: Maraviroc

Description: 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.

Arm group label: Maraviroc

Other name: Celsentri

Eligibility

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)

Gender: All

Minimum age: 18 Years

Maximum age: N/A

Healthy volunteers: No

Overall Official
Last Name Role Affiliation
Bruce J Brew, MBBS, PhD Principal Investigator St Vincent's Hospital - Sydney, Australia
Location
facility
St. Vincent's Hospital | Sydney, New South Wales, 2010, Australia
The Alfred Hospital | Melbourne, Victoria, 3181, Australia
Location Countries

Australia

Verification Date

February 2019

Responsible Party

Responsible party type: Sponsor-Investigator

Investigator affiliation: St. Vincent's Hospital-Manhattan

Investigator full name: Bruce Brew

Investigator title: Professor

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 2
Arm Group

Arm group label: Standard of care HAART regimen

Arm group type: No Intervention

Description: Participants randomised to this arm of the trial will remain on their usual prescribed HAART regimen.

Arm group label: Maraviroc

Arm group type: Experimental

Description: 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.

Acronym HANDmac
Study Design Info

Allocation: Randomized

Intervention model: Parallel Assignment

Primary purpose: Treatment

Masking: None (Open Label)

Source: ClinicalTrials.gov