HIVHANDobsNCT01434654
Efficacy of Neuro-HAART in Patients With HIV
An observational study of HIV, run by St Vincent's Hospital, Sydney at 2 sites in Australia.
Trial summary
Patients infected with Human Immunodeficiency Virus (HIV) are at risk of brain related complications despite the use of highly active antiretroviral therapy (HAART). Such complications are termed HIV neurocognitive disorders (HAND) and comprise a spectrum from asymptomatic neurocognitive impairment (ANI), through mild… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- HIV
- How many people
- 19 participants
- Where
- 2 sitesAustralia
- Study dates
- Sep 2011to Sep 2014
- Phase
- Observational
- 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
Study population: HIV positive participants on HAART who attend outpatient primary care clinics.
Who may be able to join
- HIV positive with nadir cluster of differentiation 4 (CD4) count <350 /microlitre (uL)
- Taking HAART with CNS Penetration Effectiveness (CPE) score of either ≤7.0 or ≥7.5 for 1 year or more. Changes in antiretrovirals (ARVs) within the last 12 months are allowed so long as the CPE score does not lead to a change groups
- Plasma HIV viral load <50 copies / mL for preceding 12 months or longer
- Informed consent given by participant or legally appointed guardian
Who cannot join
- Non-HIV related neurological disorders and active CNS opportunistic infection as assessed by full blood count, electrolytes, creatinine, glucose, liver function tests, cryptococcal antigen, venereal disease reaction level (VDRL), MRI brain scan and cerebrospinal fluid analyses for cell count, protein, glucose, culture, VDRL and cryptococcal antigen.
- Psychiatric disorders on the psychotic axis, current major depression, and current substance use disorder as assessed by the Study Enrolment Questionnaire for Eligibility
- Severe substance use disorders (within 12 months of study entry)
- Active Hepatitis C virus (HCV) (detectable HCV RNA because HCV per se can cause cognitive impairment)
- History of loss of consciousness >1 hour
- Non-proficient in English as assessed by the "English as a second language questionnaire"
- Medications known pharmacologically to interact with ARVs
- Pregnancy as assessed by the urinary pregnancy test
Trial locations and contacts
2 sites in 1 country.
Australia2 sites
The Alfred Hospital
Prahran, Victoria, 3181
St Vincent's Hospital
Sydney, New South Wales, 2010
About this study
Official title: The Efficacy of Neuro-HAART in HIV Infected Individuals
Patients infected with Human Immunodeficiency Virus (HIV) are at risk of brain related complications despite the use of highly active antiretroviral therapy (HAART). Such complications are termed HIV neurocognitive disorders (HAND) and comprise a spectrum from asymptomatic neurocognitive impairment (ANI), through mild cognitive impairment (MCI) to severe HIV dementia (HAD).
Prior to HAART approximately 30% of patients with advanced HIV disease had cognitive impairment; with HAART the incidence of HAND has decreased but its prevalence increased. The reasons for the ongoing development of cognitive impairment in HAART treated patients are not clear. They might relate to virus induced brain injury prior to starting HAART, the onset of a separate neurological process, toxicity related to HAART, or ongoing viral infection in the brain.
Read more
It is clear that the ability of different antiretroviral drugs to penetrate the brain varies but what is not established is whether these differences between drugs lead to different neurological outcomes. The investigators propose to study HIV infected patients stable on HAART for 12 months; subdividing the groups according to the brain penetrance of their drug combination. Patients would undergo neuropsychological assessment and MRI brain scan at the start of the study and after 12 months.
Differences in neuropsychological tests and MRI would be sought between treatment groups to establish whether HAART with better CNS penetration is associated with better outcome and fewer MRI changes.
- Conditions
- HIV
- Keywords
- HAND, HIV, Neurology, Neurocognitive, Neuro-HAART, HIV Associated Neurocognitive Disorders (HAND)
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Non Neuro-HAART (low CNS penetrance) | Participants will be assessed based on their current Highly Active Antiretroviral Treatment (HAART). A scoring system is utilised to determine if their current treatment has high Central Nervous System (CNS) penetrance or low CNS penetrance. This will determine which study cohort they are allocated to. No treatment adjustments or changes will be made, they will remain on their usual HAART regimen. | |
| Neuro-HAART (high CNS penetrance) | Participants will be assessed based on their current Highly Active Antiretroviral Treatment (HAART). A scoring system is utilised to determine if their current treatment has high Central Nervous System (CNS) penetrance or low CNS penetrance. This will determine which study cohort they are allocated to. No treatment adjustments or changes will be made, they will remain on their usual HAART regimen. |
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, after a 12-month period of observation, between HIV positive patients taking antiretroviral regimens categorized as being either of high or low CNS penetration. To derive this score, 1) raw scores obtained from a 5-domain brief neurocognitive battery were converted to age-corrected z-scores (M=0, Standard Deviation=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: Change from baseline Neuropsychological testing at 6 and 12 months
Secondary outcomes (3)
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), after a 12 month period of observation. Spectra were acquired on a Phillips Achieva 3T MRI scanner using point-resolved spectroscopy (PRESS) sequence with short echo 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 H20 as standard.
Measured: Baseline and 12 months
Cerebrospinal Fluid
To measure plateaux CSF ARV concentrations. This will identify the proportion of patients achieving levels of specific ARVs capable of inhibiting 95% of in vitro viral replication (IC95).
Measured: Baseline to 12 Months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Sep 2011 (estimated)
- Study startSep 2011
- Primary completionSep 2014
- Study completionSep 2014
Why it stopped: Slower than expected recruitment
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.
- Other trials for HIVStudies 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 19 participants (actual)
Sponsor and investigators
- Lead sponsor
- St Vincent's Hospital, Sydney
- Sponsor type
- University, hospital or other
- Collaborators
- ViiV Healthcare
- Responsible party
- Principal investigator, Bruce Brew, St Vincent's Hospital, Sydney
- Investigators
- Bruce J Brew, MBBS, PhD, Principal investigator, St Vincent's Hospital, Sydney
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01434654
- Sponsor's protocol ID
- 09/192
- Other IDs
- COL114560
- Acronym
- HANDobs
- Status last verified
- Jul 2016
- First submitted
- 12 Sep 2011
- Last updated
- 9 Aug 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Aug 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Efficacy of Neuro-HAART in HIV Infected Individuals
- ClinicalTrials.gov ID
- NCT01434654
- Acronym / sponsor ID
- HANDobs / 09/192
- Conditions
- HIV
- Keywords
- HAND, HIV, Neurology, Neurocognitive, Neuro-HAART, HIV Associated Neurocognitive Disorders (HAND)
- Study type
- Observational
- Recruitment status
- TerminatedReason stopped: Slower than expected recruitment
- Enrolment
- 19 participants (actual)
- Lead sponsor
- St Vincent's Hospital, SydneyUniversity, hospital or other
- Collaborators
- ViiV Healthcare
- Study start
- Sep 2011
- Primary completion
- Sep 2014 (actual)
- Study completion
- Sep 2014 (actual)
- First posted
- 15 Sep 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.
Patients infected with Human Immunodeficiency Virus (HIV) are at risk of brain related complications despite the use of highly active antiretroviral therapy (HAART). Such complications are termed HIV neurocognitive disorders (HAND) and comprise a spectrum from asymptomatic neurocognitive impairment (ANI), through mild cognitive impairment (MCI) to severe HIV dementia (HAD).
Prior to HAART approximately 30% of patients with advanced HIV disease had cognitive impairment; with HAART the incidence of HAND has decreased but its prevalence increased. The reasons for the ongoing development of cognitive impairment in HAART treated patients are not clear. They might relate to virus induced brain injury prior to starting HAART, the onset of a separate neurological process, toxicity related to HAART, or ongoing viral infection in the brain.
It is clear that the ability of different antiretroviral drugs to penetrate the brain varies but what is not established is whether these differences between drugs lead to different neurological outcomes. The investigators propose to study HIV infected patients stable on HAART for 12 months; subdividing the groups according to the brain penetrance of their drug combination. Patients would undergo neuropsychological assessment and MRI brain scan at the start of the study and after 12 months.
Differences in neuropsychological tests and MRI would be sought between treatment groups to establish whether HAART with better CNS penetration is associated with better outcome and fewer MRI changes.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Non Neuro-HAART (low CNS penetrance) | – | –Participants will be assessed based on their current Highly Active Antiretroviral Treatment (HAART). A scoring system is utilised to determine if their current treatment has high Central Nervous System (CNS) penetrance or low CNS penetrance. This will determine which study cohort they are allocated to. No treatment adjustments or changes will be made, they will remain on their usual HAART regimen. |
| Neuro-HAART (high CNS penetrance) | – | –Participants will be assessed based on their current Highly Active Antiretroviral Treatment (HAART). A scoring system is utilised to determine if their current treatment has high Central Nervous System (CNS) penetrance or low CNS penetrance. This will determine which study cohort they are allocated to. No treatment adjustments or changes will be made, they will remain on their usual HAART regimen. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- HIV positive participants on HAART who attend outpatient primary care clinics.
Key inclusion criteria (4 listed)
- HIV positive with nadir cluster of differentiation 4 (CD4) count <350 /microlitre (uL)
- Taking HAART with CNS Penetration Effectiveness (CPE) score of either ≤7.0 or ≥7.5 for 1 year or more. Changes in antiretrovirals (ARVs) within the last 12 months are allowed so long as the CPE score does not lead to a change groups
- Plasma HIV viral load <50 copies / mL for preceding 12 months or longer
- Informed consent given by participant or legally appointed guardian
Key exclusion criteria (8 listed)
- Non-HIV related neurological disorders and active CNS opportunistic infection as assessed by full blood count, electrolytes, creatinine, glucose, liver function tests, cryptococcal antigen, venereal disease reaction level (VDRL), MRI brain scan and cerebrospinal fluid analyses for cell count, protein, glucose, culture, VDRL and cryptococcal antigen.
- Psychiatric disorders on the psychotic axis, current major depression, and current substance use disorder as assessed by the Study Enrolment Questionnaire for Eligibility
- Severe substance use disorders (within 12 months of study entry)
- Active Hepatitis C virus (HCV) (detectable HCV RNA because HCV per se can cause cognitive impairment)
- History of loss of consciousness >1 hour
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Change in Neurocognitive Functioning
Time frame: Change from baseline Neuropsychological testing at 6 and 12 months
Change in overall neurocognitive performance, defined as a global neurocognitive z-score, after a 12-month period of observation, between HIV positive patients taking antiretroviral regimens categorized as being either of high or low CNS penetration. To derive this score, 1) raw scores obtained from a 5-domain brief neurocognitive battery were converted to age-corrected z-scores (M=0, Standard Deviation=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 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
Cerebrospinal Fluid
Time frame: Baseline to 12 Months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Aug 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of HIV, run by St Vincent's Hospital, Sydney 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 8 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: stopped early, as of the sponsor's last update on 9 Aug 2016. 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.
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: Change from baseline Neuropsychological testing at 6 and 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 9 Aug 2016.