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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT01449006




Registration number
NCT01449006
Ethics application status
Date submitted
6/10/2011
Date registered
7/10/2011
Date last updated
27/02/2019

Titles & IDs
Public title
A Study of the Neurological Effects of Adding Maraviroc to HAART Regimen in Patients With HIV (HANDmac)
Scientific title
A Randomised Controlled Clinical Trial of the Efficacy of HAART Intensification With Maraviroc in HIV Virally Suppressed Patients With Cognitive Impairment
Secondary ID [1] 0 0
114560
Secondary ID [2] 0 0
11/066
Universal Trial Number (UTN)
Trial acronym
HANDmac
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Human Immunodeficiency Virus (HIV) 0 0
HIV Associated Neurocognitive Disorders (HAND) 0 0
Condition category
Condition code
Infection 0 0 0 0
Acquired immune deficiency syndrome (AIDS / HIV)
Neurological 0 0 0 0
Other neurological disorders
Mental Health 0 0 0 0
Other mental health disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Maraviroc

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.


Treatment: Drugs: 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.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Change in Neurocognitive Functioning
Timepoint [1] 0 0
Baseline, 6-months and 12-months
Secondary outcome [1] 0 0
Change in CSF Neopterin Concentration
Timepoint [1] 0 0
Baseline and 12-months
Secondary outcome [2] 0 0
Change in MRS Cerebral Metabolite Ratios in Basal Ganglia
Timepoint [2] 0 0
Baseline and 12 months
Secondary outcome [3] 0 0
Change in MRS Cerebral Metabolite Ratios in Frontal White Matter
Timepoint [3] 0 0
Baseline and 12 months

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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 design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/10/2011
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/09/2014
Sample size
Target
Accrual to date
Final
19
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
St. Vincent's Hospital - Sydney
Recruitment hospital [2] 0 0
The Alfred Hospital - Melbourne
Recruitment postcode(s) [1] 0 0
2010 - Sydney
Recruitment postcode(s) [2] 0 0
3181 - Melbourne

Funding & Sponsors
Primary sponsor type
Other
Name
Bruce Brew
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
ViiV Healthcare
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT01449006
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Bruce J Brew, MBBS, PhD
Address 0 0
St Vincent's Hospital - Sydney, Australia
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT01449006