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

This study is not yet open for participant recruitment.
Verified October 2012 by St Vincent's Hospital, Sydney
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: October 7, 2012
Last verified: October 2012
History of Changes
  Purpose

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. At study initiation a lumbar puncture would be performed so that drugs levels could be measured in CSF.

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.


Condition
HIV

Study Type: Observational
Study Design: Time Perspective: Prospective
Official Title: The Efficacy of Neuro-HAART in HIV Infected Individuals

Resource links provided by NLM:

MedlinePlus related topics: HIV/AIDS
U.S. FDA Resources

Further study details as provided by St Vincent's Hospital, Sydney:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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.


Biospecimen Retention:   Samples Without DNA

Cerbrospinal fluid and bloods


Estimated Enrollment: 170
Study Start Date: September 2011
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 randomised 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 randomised to. No treatment adjustments or changes will be made, they will remain on their usual HAART regimen.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

HIV positive participants on HAART who attend outpatient primary care clinics.

Criteria

Inclusion Criteria:

  • HIV positive with nadir CD4 count <350 /uL
  • Taking HAART with CNS Penetration Effectiveness (CPE) score of either ≤7.0 or ≥7.5 for 1 year or more. Changes in 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, 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 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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01434654

Contacts
Contact: Bruce J Brew, MBBS, PhD 61 2 8382 1111 ext 4100 bbrew@stvincents.com.au
Contact: Krista J Siefried, RN 61 2 8382 1111 ext 2668 ksiefried@stvincents.com.au

Locations
Australia, New South Wales
St Vincent's Hospital Recruiting
Sydney, New South Wales, Australia, 2010
Principal Investigator: Bruce J Brew, MBBS, PhD            
Australia, Victoria
The Alfred Hospital Not yet recruiting
Prahran, Victoria, Australia, 3181
Contact: Edwina Wright, MBBS     61 3 9076 6078     e.wright@alfred.org.au    
Sponsors and Collaborators
St Vincent's Hospital, Sydney
ViiV Healthcare
Investigators
Principal Investigator: Bruce J Brew, MBBS, PhD St Vincent's Hospital, Sydney
  More Information

No publications provided

Responsible Party: Bruce Brew, Professor, St Vincent's Hospital, Sydney
ClinicalTrials.gov Identifier: NCT01434654     History of Changes
Other Study ID Numbers: 09/192, COL114560
Study First Received: September 12, 2011
Last Updated: October 7, 2012
Health Authority: Australia: Human Research Ethics Committee

Keywords provided by St Vincent's Hospital, Sydney:
HAND
HIV
Neurology
 Neurocognitive
Neuro-HAART
HIV Associated Neurocognitive Disorders (HAND)

ClinicalTrials.gov processed this record on May 22, 2013