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

Tracking Information
First Submitted Date ICMJE	October 5, 2011
First Posted Date ICMJE	October 7, 2011
Results First Submitted Date	November 13, 2013
Results First Posted Date	January 3, 2014
Last Update Posted Date	June 27, 2016
Study Start Date ICMJE	October 2011
Actual Primary Completion Date	October 2013 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: May 19, 2016)	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.
Original Primary Outcome Measures ICMJE; (submitted: October 5, 2011)	Neurocognitive Function [ Time Frame: Change from baseline neuropsychological testing, at 6 months, and at 12 months ]; The primary endpoint is improvement on overall neuropsychological performance defined as a reliable change score index (RCI) corrected for practice effect.
Change History	Complete list of historical versions of study NCT01448486 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE; (submitted: May 19, 2016)	Cerebrospinal Fluid [ Time Frame: Baseline and 12 months ]; To determine if there is improvement in CSF neopterin concentrations with the addition of Raltegravir.
Original Secondary Outcome Measures ICMJE; (submitted: October 5, 2011)	Cerebrospinal Fluid [ Time Frame: Change in Neopterin concentrations in CSF from baseline to 12 months ]; To determine if there is improvement in CSF neopterin concentrations with the addition of Raltegravir.
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	A Study of the Neurological Effects of Adding Raltegravir to HAART Regimen in Patients With HIV
Official Title ICMJE	A Randomised Controlled Clinical Trial of the Efficacy of HAART Intensification With Raltegravir in HIV Virally Suppressed Patients With Cognitive Impairment
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.
Detailed Description	Not Provided
Study Type ICMJE	Interventional
Study Phase	Phase 4
Study Design ICMJE	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Condition ICMJE	Human Immunodeficiency Virus (HIV); HIV Associated Neurocognitive Disorders (HAND)
Intervention ICMJE	Drug: Raltegravir; Oral raltegravir, 400 mg tablet, twice daily for one year.; Other Name: Isentress
Study Arms	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
Publications *	Not Provided
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Terminated
Actual Enrollment ICMJE; (submitted: November 13, 2013)	6
Original Estimated Enrollment ICMJE; (submitted: October 5, 2011)	220
Actual Study Completion Date	October 2013
Actual Primary Completion Date	October 2013 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	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)
Sex/Gender	Sexes Eligible for Study: All
Ages	18 Years and older (Adult, Senior)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	Australia
Removed Location Countries
Administrative Information
NCT Number ICMJE	NCT01448486
Other Study ID Numbers ICMJE	11/033; IISP 37693 ( Other Grant/Funding Number: Merck Sharp & Dohme )
Has Data Monitoring Committee	Yes
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	Bruce Brew, St Vincent's Hospital, Sydney
Study Sponsor ICMJE	St Vincent's Hospital, Sydney
Collaborators ICMJE	Merck Sharp & Dohme Corp.
Investigators ICMJE	Principal Investigator: Bruce J Brew, MBBS, PhD St Vincent's Hospital, Sydney
PRS Account	St Vincent's Hospital, Sydney
Verification Date	May 2016
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP