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Efficacy of Neuro-HAART in Patients With HIV (HANDobs)

This study has been terminated.
(Slower than expected recruitment)
Sponsor:
Collaborator:
ViiV Healthcare
Information provided by (Responsible Party):
Bruce Brew, St Vincent's Hospital, Sydney
ClinicalTrials.gov Identifier:
NCT01434654
First received: September 12, 2011
Last updated: July 6, 2016
Last verified: July 2016

September 12, 2011
July 6, 2016
September 2011
September 2014   (final data collection date for primary outcome measure)
Change in Neurocognitive Functioning [ Time Frame: Change from baseline Neuropsychological testing at 6 and 12 months ] [ Designated as safety issue: No ]
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.
Neurocognitive Function [ Time Frame: Change from baseline Neuropsychological testing, at 12 months ] [ Designated as safety issue: No ]
To compare the change in summary neuropsychological 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.
Complete list of historical versions of study NCT01434654 on ClinicalTrials.gov Archive Site
  • Change in MRS Cerebral Metabolite Ratios in Basal Ganglia [ Time Frame: Baseline and 12 months ] [ Designated as safety issue: No ]
    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.
  • Change in MRS Cerebral Metabolite Ratios in Frontal White Matter [ Time Frame: Baseline and 12 months ] [ Designated as safety issue: No ]
    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.
  • Cerebrospinal Fluid [ Time Frame: Baseline to 12 Months ] [ Designated as safety issue: No ]
    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).
  • Magnetic Resonance Imaging (MRI - Brain) [ Time Frame: Change from baseline MRI, at 12 months ] [ Designated as safety issue: No ]
    To compare the change in brain magnetic resonance spectroscopy in predefined regions of interest, after a 12-month period of observation, between HIV positive patients taking antiretroviral regimens categorized as being either of high or low CNS penetration.
  • Cerebrospinal Fluid [ Time Frame: Change in CNS penetrance of ARV medications from baseline to 12 months ] [ Designated as safety issue: No ]
    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); and will be correlated with the neuropsychological and MR spectroscopy outcome measures. Additionally, to ascertain whether pharmacokinetic interactions between ARVs affect CSF levels of the individual drugs.
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Not Provided
 
Efficacy of Neuro-HAART in Patients With HIV
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.

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.

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Observational
Observational Model: Cohort
Time Perspective: Prospective
Not Provided
Retention:   Samples Without DNA
Description:
Cerbrospinal fluid and bloods
Non-Probability Sample
HIV positive participants on HAART who attend outpatient primary care clinics.
HIV
Not Provided
  • 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.
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
19
September 2014
September 2014   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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
Both
18 Years and older   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
Australia
 
NCT01434654
09/192, COL114560
No
Not Provided
Not Provided
Bruce Brew, St Vincent's Hospital, Sydney
St Vincent's Hospital, Sydney
ViiV Healthcare
Principal Investigator: Bruce J Brew, MBBS, PhD St Vincent's Hospital, Sydney
St Vincent's Hospital, Sydney
July 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP