Neurocognitive Effects and Tolerability of Efavirenz in Aging HIV-infected Individuals ("SHAC Neuro Study")

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01985399
Recruitment Status : Completed
First Posted : November 15, 2013
Last Update Posted : October 17, 2016
Janssen Services, LLC
Information provided by (Responsible Party):
Philip Grant, Stanford University

Brief Summary:
Investigators hypothesize that older HIV-infected individuals (i.e., >50 years old) on efavirenz (EFV)-containing antiretroviral therapy (ART) will have significantly worse neurocognitive function than older individuals on non-EFV-containing ART.

Condition or disease Intervention/treatment
HIV AIDS Behavioral: Neuropsychological testing

Detailed Description:

With the aging of the HIV-infected population in the United States and elsewhere, neurocognitive dysfunction will likely become an increasingly common problem. Older individuals could be at increased risk for efavirenz-associated adverse effects due to impaired metabolism, increased drug-drug interactions, and lower physiologic reserve, but there are few data on the long-term safety of efavirenz (and other antiretrovirals) in older individuals with HIV.

The Stanford HIV Aging Cohort (SHAC) is an ideal setting to study potential neurologic effects of antiretrovirals in aging patients. SHAC is an ongoing longitudinal study initiated in 2008 to evaluate aging in virologically-suppressed HIV-infected individuals. The cohort is supported through multiple grants including a grant from the State of California's HIV Research Program as well as a NIH supplemental grant. As of September 2013, approximately 150 virologically-suppressed HIV-infected adults have been enrolled. In addition to enrolling patients with good adherence to ART, the cohort purposefully excludes subjects with active substance abuse, unstable medical conditions, and psychiatric illnesses to limit potential confounding the study end points. Recently, an NIH supplemental grant (AI069556) was received which will expand the SHAC to 300 HIV-infected subjects. The median age of the subjects in the cohort is in the mid-50's allowing an ample number of older subjects for our planned studies.

Study Type : Observational
Actual Enrollment : 100 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Neurocognitive Effects and Tolerability of Efavirenz in Aging HIV-infected Individuals ("SHAC Neuro Study")
Study Start Date : December 2013
Actual Primary Completion Date : December 2015
Actual Study Completion Date : December 2015

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS
Drug Information available for: Efavirenz

Group/Cohort Intervention/treatment
EFV containing ARV regimen
Pts on Efavirenz containing ARV regimen will have neuropsychological testing performed
Behavioral: Neuropsychological testing
Neuropsychological testing

Non -EFV ontaning ARV regimen
Pts on a Non-Efavirenz containing ARVregimen will have neuropsychological testing measures performed
Behavioral: Neuropsychological testing
Neuropsychological testing

Primary Outcome Measures :
  1. Compare a composite measure of neurocognitive function in older individuals on EFV-containing ART vs. non-EFV-containing ART. [ Time Frame: one year ]

    Neurocognitive function will be assessed using a detailed battery of neuropsychologic tests including timed gait, grooved pegboard with the dominant and non-dominant hands, the Rey auditory verbal learning test trials I-VII, trail making parts A and B, Rey auditory verbal learning test trial VIII 30-min delay, controlled oral word association test and paced auditory serial addition task. This battery has been used extensively in previous studies in HIV. Z-scores for each neurocognitive test, based on age-adjusted norms, and a composite Z-score will be calculated. The Z-score represents the amount, in standard deviation units, that the subject's test result deviates from population means.

    In addition to neurocognitive function, the level of depression and anxiety and sleep quality will be evaluated using validated instruments.

Information from the National Library of Medicine

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Ages Eligible for Study:   50 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population
50 individuals on an EFV-containing regimen and 50 individuals on a protease-inhibitor (PI)-containing regimen

Inclusion Criteria:

  • Enrollment into SHAC (Stanford HIV Aging cohort)
  • Age over 50 years of age
  • Stable antiretroviral therapy containing EFV- or PI-containing ART (but not both) for at least 6 months
  • HIV RNA levels of <200 copies/mL for at least 6 months excluding blips (i.e., a single measurement between 200-500 copies/mL preceded and followed by measurements of <200 copies/mL) while on ART.

Exclusion Criteria:

  • Completed treatment for any acute systemic infection (other than HIV-1) less than four weeks before study entry
  • Any active brain infection (except for HIV-1), brain neoplasm, or space-occupying brain lesion.
  • Any active psychiatric illness including schizophrenia, severe depression, or severe bipolar affective disorder that, in the opinion of the investigator, could confound the analysis of the neuropsychological test results.
  • Active drug or alcohol abuse that, in the investigator's opinion, could prevent compliance with study procedures or confound the analysis of study endpoints.
  • Hospitalization within 30 days of study entry
  • Receipt of systemic chemotherapy within 30 days of study entry
  • Unable to provide informed consent

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01985399

United States, California
Stanford University AIDS Clinical Trials Unit
Palo Alto, California, United States, 94304
Sponsors and Collaborators
Stanford University
Janssen Services, LLC
Principal Investigator: Philip Grant, MD Stanford University

Responsible Party: Philip Grant, Principle Investigator, Stanford University Identifier: NCT01985399     History of Changes
Other Study ID Numbers: SHAC Neuro Study
First Posted: November 15, 2013    Key Record Dates
Last Update Posted: October 17, 2016
Last Verified: October 2016

Keywords provided by Philip Grant, Stanford University:

Additional relevant MeSH terms:
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Cytochrome P-450 CYP2C9 Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Cytochrome P-450 CYP2C19 Inhibitors
Cytochrome P-450 CYP2B6 Inducers
Cytochrome P-450 Enzyme Inducers
Cytochrome P-450 CYP3A Inducers