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

NCT01449006 | Completed Phase 4 Results DMC

• 2 other identifiers: 11/066114560
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 2

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.

Conditions

Human Immunodeficiency Virus (HIV); HIV Associated Neurocognitive Disorders (HAND)

Keywords

HIV; HAND; Maraviroc; Neurocognitive; Neurology; Human Immunodeficiency Virus; HIV Associated Neurocognitive Disorders

Outcome Measures

Primary Outcomes (1)

• Change in Neurocognitive Functioning

  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 Outcomes (3)

• 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

Study Arms (2)

Standard of care HAART regimen

NO INTERVENTION

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

Maraviroc

EXPERIMENTAL

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

Interventions

Maraviroc DRUG

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.

Also known as: Celsentri

Maraviroc

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Bruce Brew: lead
• ViiV Healthcare: collaborator

Study Sites (2)

St. Vincent's Hospital

Sydney, New South Wales, 2010, Australia

Location

The Alfred Hospital

Melbourne, Victoria, 3181, Australia

Location

Related Publications (1)

• Gates TM, Cysique LA, Siefried KJ, Chaganti J, Moffat KJ, Brew BJ. Maraviroc-intensified combined antiretroviral therapy improves cognition in virally suppressed HIV-associated neurocognitive disorder. AIDS. 2016 Feb 20;30(4):591-600. doi: 10.1097/QAD.0000000000000951.

  PMID: 26825032 RESULT

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome

Interventions

Maraviroc

Condition Hierarchy (Ancestors)

HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Limitations and Caveats

1. Small pilot sample size (N=17). 2. Unrepresentative of international HAND populations. 3. Open-label design may have contributed to loss to follow-up in controls. 4. Modified intention-to-treat design potentially introduced bias into analyses.

Results Point of Contact

• Title: Prof. Bruce Brew
• Organization: St Vincent's Hospital, Sydney, Australia

bruce.brew@svha.org.au

61 2 8382 1111

Study Officials

• Bruce J Brew, MBBS, PhD

  St Vincent's Hospital - Sydney, Australia

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: October 6, 2011
• First Posted: October 7, 2011
• Study Start: October 1, 2011
• Primary Completion: September 1, 2014
• Study Completion: September 1, 2014
• Last Updated: February 27, 2019
• Results First Posted: May 20, 2016

Record last verified: 2019-02

Locations

AU (2)