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

This study has been terminated.
(Funding withdrawn based on unacceptably slow recruitment rate.)
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Bruce Brew, St Vincent's Hospital, Sydney
ClinicalTrials.gov Identifier:
NCT01448486
First received: October 5, 2011
Last updated: November 13, 2013
Last verified: November 2013

October 5, 2011
November 13, 2013
October 2011
October 2013   (final data collection date for primary outcome measure)
Neurocognitive Function [ Time Frame: Change from baseline neuropsychological testing, at 6 months, and at 12 months ] [ Designated as safety issue: No ]
The primary endpoint is improvement on overall neuropsychological performance defined as a reliable change score index (RCI) corrected for practice effect.
Same as current
Complete list of historical versions of study NCT01448486 on ClinicalTrials.gov Archive Site
Cerebrospinal Fluid [ Time Frame: Change in Neopterin concentrations in CSF from baseline to 12 months ] [ Designated as safety issue: No ]
To determine if there is improvement in CSF neopterin concentrations with the addition of Raltegravir.
Same as current
Not Provided
Not Provided
 
A Study of the Neurological Effects of Adding Raltegravir to HAART Regimen in Patients With HIV
A Randomised Controlled Clinical Trial of the Efficacy of HAART Intensification With Raltegravir in HIV Virally Suppressed Patients With Cognitive Impairment

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.

Not Provided
Interventional
Phase 4
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Human Immunodeficiency Virus (HIV)
  • HIV Associated Neurocognitive Disorders (HAND)
Drug: Raltegravir
Oral raltegravir, 400 mg tablet, twice daily for one year.
Other Names:
  • Raltegravir
  • Isentress
  • 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).
    Intervention: Drug: Raltegravir
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
6
October 2013
October 2013   (final data collection date for primary outcome measure)

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)
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
Australia
 
NCT01448486
11/033, IISP 37693
Yes
Bruce Brew, St Vincent's Hospital, Sydney
St Vincent's Hospital, Sydney
Merck Sharp & Dohme Corp.
Principal Investigator: Bruce J Brew, MBBS, PhD St Vincent's Hospital, Sydney
St Vincent's Hospital, Sydney
November 2013

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