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(Funding withdrawn based on unacceptably slow recruitment rate.)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
  Purpose

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 Intervention Phase
Human Immunodeficiency Virus (HIV)
HIV Associated Neurocognitive Disorders (HAND)
Drug: Raltegravir
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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

Resource links provided by NLM:


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

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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.


Enrollment: 6
Study Start Date: October 2011
Study Completion Date: October 2013
Primary Completion Date: October 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Names:
  • Raltegravir
  • Isentress

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01448486

Locations
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.
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: NCT01448486     History of Changes
Other Study ID Numbers: 11/033, IISP 37693
Study First Received: October 5, 2011
Results First Received: November 13, 2013
Last Updated: November 13, 2013
Health Authority: Australia: Human Research Ethics Committee
Australia: Department of Health and Ageing Therapeutic Goods Administration

Keywords provided by St Vincent's Hospital, Sydney:
HIV
HAND
Human Immunodeficiency Virus
Raltegravir
HIV Associated Neurocognitive Disorders
Neuro-HAART
Neurocognitive
Neurology

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
HIV Infections
Immunologic Deficiency Syndromes
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Slow Virus Diseases
Immune System Diseases

ClinicalTrials.gov processed this record on August 19, 2014