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

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ClinicalTrials.gov Identifier: NCT01434654
Recruitment Status : Terminated (Slower than expected recruitment)
First Posted : September 15, 2011
Results First Posted : May 20, 2016
Last Update Posted : August 9, 2016
Sponsor:
Collaborator:
ViiV Healthcare
Information provided by (Responsible Party):
Bruce Brew, St Vincent's Hospital, Sydney

Tracking Information
First Submitted Date September 12, 2011
First Posted Date September 15, 2011
Results First Submitted Date February 9, 2016
Results First Posted Date May 20, 2016
Last Update Posted Date August 9, 2016
Study Start Date September 2011
Actual Primary Completion Date September 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: July 6, 2016)
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.
Original Primary Outcome Measures
 (submitted: September 13, 2011)
Neurocognitive Function [ Time Frame: Change from baseline Neuropsychological testing, at 12 months ]
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.
Change History Complete list of historical versions of study NCT01434654 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures
 (submitted: May 24, 2016)
  • Change in MRS Cerebral Metabolite Ratios in Basal Ganglia [ Time Frame: Baseline and 12 months ]
    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 ]
    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 ]
    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).
Original Secondary Outcome Measures
 (submitted: September 13, 2011)
  • Magnetic Resonance Imaging (MRI - Brain) [ Time Frame: Change from baseline MRI, at 12 months ]
    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 ]
    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.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title Efficacy of Neuro-HAART in Patients With HIV
Official Title The Efficacy of Neuro-HAART in HIV Infected Individuals
Brief 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 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.

Detailed Description Not Provided
Study Type Observational
Study Design Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Retention:   Samples Without DNA
Description:
Cerbrospinal fluid and bloods
Sampling Method Non-Probability Sample
Study Population HIV positive participants on HAART who attend outpatient primary care clinics.
Condition HIV
Intervention Not Provided
Study Groups/Cohorts
  • 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.
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Terminated
Actual Enrollment
 (submitted: April 13, 2016)
19
Original Estimated Enrollment
 (submitted: September 13, 2011)
170
Actual Study Completion Date September 2014
Actual Primary Completion Date September 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria

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
Sex/Gender
Sexes Eligible for Study: All
Ages 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers No
Contacts Contact information is only displayed when the study is recruiting subjects
Listed Location Countries Australia
Removed Location Countries  
 
Administrative Information
NCT Number NCT01434654
Other Study ID Numbers 09/192
COL114560 ( Other Grant/Funding Number: VIIV Healthcare )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement Not Provided
Responsible Party Bruce Brew, St Vincent's Hospital, Sydney
Study Sponsor St Vincent's Hospital, Sydney
Collaborators ViiV Healthcare
Investigators
Principal Investigator: Bruce J Brew, MBBS, PhD St Vincent's Hospital, Sydney
PRS Account St Vincent's Hospital, Sydney
Verification Date July 2016