A Study of the Neurological Effects of Adding Raltegravir to HAART Regimen in Patients With HIV (HANDral)

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: NCT01448486
Recruitment Status : Terminated (Funding withdrawn based on unacceptably slow recruitment rate.)
First Posted : October 7, 2011
Results First Posted : January 3, 2014
Last Update Posted : June 27, 2016
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Bruce Brew, St Vincent's Hospital, Sydney

Brief Summary:

HIV related cognitive impairment still occurs despite highly active antiretroviral therapy (HAART). HIV disease affects the brain in 20-40% of patients with advancing HIV disease leading to varying degrees of cognitive impairment, recently termed HIV associated neurocognitive disorders (HAND).

HAND may occur in patients who are virally suppressed in both blood and CSF. Patients with HIV Associated Neurological Disorders (HAND) who are virally suppressed in both their blood and cerebrospinal fluid (CSF), whilst on a highly active antiretroviral therapy (HAART) regimen may have significant cognitive improvement with HAART intensification with the medication Raltegravir; compared to those who remain on their existing regimen.

This study will be a prospective, interventional, randomised and unblinded controlled clinical trial. The aim of this study will be to determine whether HAART intensification with the medication Raltegravir, leads to significant improvement in HIV associated neurological disorders (HAND).

Patients with the recent progression (within 6 months) of HAND (validated by neuropsychological assessment) on HAART who are virally suppressed (<50 copies per ml) in blood and CSF will be randomised to have their existing HAART regimen intensified with raltegravir 400mg twice daily, or not. The control arm will remain on their medication regimen as prescribed. The target is to enrol 110 patients into the control group, and 110 patients into the Raltegravir intensification group.

Patients will undergo baseline neuropsychological testing, MRI, blood tests, and cerebral spinal fluid (CSF) tests (via a lumbar puncture). The methods used to determine the effectiveness of adding Raltegravir, will include further neuropsychological testing at 6 months; and neuropsychological testing, MRI and CSF assessment at 12 months. Neuropsychological testing completed at 6 and 12 months will be completed by a "blind assessor", in that they will have no knowledge of which arm (treatment or control) the participant is enrolled in.

An evaluation (neuropsychological testing) will be performed should the patient deteriorate during the course of the study, as recognised by the patient's managing physician. The decision of the Antiretroviral medication regimen to be used in such a case will be determined by the managing physician. At the end of the study protocol (12 months) the patient's HAART therapy will be managed by their primary physician.

Condition or disease Intervention/treatment Phase
Human Immunodeficiency Virus (HIV) HIV Associated Neurocognitive Disorders (HAND) Drug: Raltegravir Phase 4

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 6 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Randomised Controlled Clinical Trial of the Efficacy of HAART Intensification With Raltegravir in HIV Virally Suppressed Patients With Cognitive Impairment
Study Start Date : October 2011
Actual Primary Completion Date : October 2013
Actual Study Completion Date : October 2013

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

Arm Intervention/treatment
No Intervention: Standard of Care HAART
Participants randomised to this arm will remain on their standard of care Highly Active Antiretroviral Therapy (HAART).
Experimental: Raltegravir
Participants randomised to this arm will remain on their standard of care Highly Active Antiretroviral Therapy (HAART) with the addition of Raltegravir 400 mg twice daily (BID).
Drug: Raltegravir
Oral raltegravir, 400 mg tablet, twice daily for one year.
Other Name: Isentress

Primary Outcome Measures :
  1. Neurocognitive Function [ Time Frame: Baseline, 6 months and 12 months ]
    Change in overall neurocognitive performance, defined as a global neurocognitive z-score, over the study time-period (baseline, 6-months, 12-months). To derive this score, 1) raw scores obtained from a 5-domain brief neurocognitive battery were converted to age-corrected z-scores (M=0, SD=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.

Secondary Outcome Measures :
  1. Cerebrospinal Fluid [ Time Frame: Baseline and 12 months ]
    To determine if there is improvement in CSF neopterin concentrations with the addition of Raltegravir.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • HIV positive
  • On HAART, with plasma HIV viral load < 50 copies/ml for previous 12 months or more
  • Able to provide informed consent
  • HAND diagnosis, with symptom progression within previous 6 months (while on existing HAART regimen)

Exclusion Criteria:

  • Non-HIV related neurological disorders and active CNS opportunistic infection (as assessed by full blood count, electrolytes, creatinine, glucose, LFT's, cryptococcal antigen, VDRL, MRI brain scan and CSF fluid analysis for cell count, protein, glucose, culture, VDRL and cryptococcal antigen)
  • Psychiatric disorders on the psychotic axis
  • Current major depression
  • Current substance use disorder, or severe substance use disorders within 12 months of study entry
  • Active HCV (detectable HCV RNA)
  • History of loss of consciousness > 1 hour
  • Non-proficient in English
  • Medications known to pharmacologically interact with ARV's
  • Currently taking an Integrase Inhibitor
  • Pregnancy (as assessed by the urine pregnancy test)

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): NCT01448486

Australia, New South Wales
St. Vincent's Hospital
Sydney, New South Wales, Australia, 2010
Australia, Victoria
The Alfred Hospital
Melbourne, Victoria, Australia, 3181
Sponsors and Collaborators
St Vincent's Hospital, Sydney
Merck Sharp & Dohme Corp.
Principal Investigator: Bruce J Brew, MBBS, PhD St Vincent's Hospital, Sydney

Responsible Party: Bruce Brew, Professor, St Vincent's Hospital, Sydney Identifier: NCT01448486     History of Changes
Other Study ID Numbers: 11/033
IISP 37693 ( Other Grant/Funding Number: Merck Sharp & Dohme )
First Posted: October 7, 2011    Key Record Dates
Results First Posted: January 3, 2014
Last Update Posted: June 27, 2016
Last Verified: May 2016

Keywords provided by Bruce Brew, St Vincent's Hospital, Sydney:
Human Immunodeficiency Virus
HIV Associated Neurocognitive Disorders

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
HIV Infections
Immunologic Deficiency Syndromes
Neurocognitive Disorders
Immune System Diseases
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Slow Virus Diseases
Mental Disorders
Raltegravir Potassium
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
HIV Integrase Inhibitors
Integrase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action