Human Immunodeficiency Virus (HIV)Phase 4HANDmacNCT01449006
A Study of the Neurological Effects of Adding Maraviroc to HAART Regimen in Patients With HIV (HANDmac)
A Phase 4 study testing Maraviroc in people with Human Immunodeficiency Virus (HIV) and HIV Associated Neurocognitive Disorders (HAND), run by Bruce Brew at 2 sites in Australia.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Human Immunodeficiency Virus (HIV), HIV Associated Neurocognitive Disorders (HAND)
- What is being tested?
- Maraviroc
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 19 participants
- Where
- 2 sitesAustralia
- Study dates
- Oct 2011to Sep 2014
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 10Show fewer
- 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)
Trial locations and contacts
2 sites in 1 country.
Australia2 sites
The Alfred Hospital
Melbourne, Victoria, 3181
St. Vincent's Hospital
Sydney, New South Wales, 2010
About this study
Official title: 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.
Read more
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.
- Being tested
- Maraviroc
- Keywords
- HIV, HAND, Maraviroc, Neurocognitive, Neurology, Human Immunodeficiency Virus, HIV Associated Neurocognitive Disorders
- Medical subject headings
- Acquired Immunodeficiency Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MaravirocDrug
Also called Celsentri
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Maraviroc |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline, 6-months and 12-months
Secondary outcomes (3)
Change in CSF Neopterin Concentration
Change in concentration of the CSF neuroinflammatory marker neopterin (measured in nmol/L) from baseline to 12-months.
Measured: Baseline and 12-months
Change in MRS Cerebral Metabolite Ratios in Basal Ganglia
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.
Measured: Baseline and 12 months
Change in MRS Cerebral Metabolite Ratios in Frontal White Matter
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.
Measured: Baseline and 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Oct 2011 (estimated)
- Study startOct 2011
- Primary completionSep 2014
- Study completionSep 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Human Immunodeficiency Virus (HIV)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 19 participants (actual)
Sponsor and investigators
- Lead sponsor
- Bruce Brew
- Sponsor type
- University, hospital or other
- Collaborators
- ViiV Healthcare
- Responsible party
- Sponsor-investigator, Bruce Brew, St Vincent's Hospital
- Investigators
- Bruce J Brew, MBBS, PhD, Principal investigator, St Vincent's Hospital - Sydney, Australia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01449006
- Sponsor's protocol ID
- 11/066
- Other IDs
- 114560
- Acronym
- HANDmac
- Status last verified
- Feb 2019
- First submitted
- 6 Oct 2011
- Last updated
- 27 Feb 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 26825032
Study at a glance
From the registry record, last updated by the sponsor on 27 Feb 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomised Controlled Clinical Trial of the Efficacy of HAART Intensification With Maraviroc in HIV Virally Suppressed Patients With Cognitive Impairment
- ClinicalTrials.gov ID
- NCT01449006
- Acronym / sponsor ID
- HANDmac / 11/066
- Keywords
- HIV, HAND, Maraviroc, Neurocognitive, Neurology, Human Immunodeficiency Virus, HIV Associated Neurocognitive Disorders
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 19 participants (actual)
- Lead sponsor
- Bruce BrewUniversity, hospital or other
- Collaborators
- ViiV Healthcare
- Study start
- Oct 2011
- Primary completion
- Sep 2014 (actual)
- Study completion
- Sep 2014 (actual)
- First posted
- 7 Oct 2011 (estimated)
- Results
- Posted 20 May 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 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 | Drug: MaravirocParticipants 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (10 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MaravirocAlso: CelsentriMaraviroc 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. | Drug | Maraviroc |
Primary outcome
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.
3 secondary outcomes
Change in CSF Neopterin Concentration
Time frame: Baseline and 12-months
Change in MRS Cerebral Metabolite Ratios in Basal Ganglia
Time frame: Baseline and 12 months
Change in MRS Cerebral Metabolite Ratios in Frontal White Matter
Time frame: Baseline and 12 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Feb 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 26825032Gates 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Bruce J Brew, MBBS, PhD principal investigator
St Vincent's Hospital - Sydney, Australia
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Maraviroc in people with Human Immunodeficiency Virus (HIV) and HIV Associated Neurocognitive Disorders (HAND), run by Bruce Brew at 2 sites in Australia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Feb 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Australia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 20 May 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Neurocognitive Functioning (time frame: Baseline, 6-months and 12-months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01449006, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Feb 2019.