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

NCT01448486 | Terminated Phase 4 Results DMC

• 2 other identifiers: 11/033IISP 37693
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 2

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.

Conditions

Human Immunodeficiency Virus (HIV); HIV Associated Neurocognitive Disorders (HAND)

Keywords

HIV; HAND; Human Immunodeficiency Virus; Raltegravir; HIV Associated Neurocognitive Disorders; Neuro-HAART; Neurocognitive; Neurology

Outcome Measures

Primary Outcomes (1)

• Neurocognitive Function

  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.

  Baseline, 6 months and 12 months

Secondary Outcomes (1)

• Cerebrospinal Fluid

  Baseline and 12 months

Study Arms (2)

Standard of Care HAART

NO INTERVENTION

Participants randomised to this arm will remain on their standard of care Highly Active Antiretroviral Therapy (HAART).

Raltegravir

EXPERIMENTAL

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

Interventions

Raltegravir DRUG

Oral raltegravir, 400 mg tablet, twice daily for one year.

Also known as: Isentress

Raltegravir

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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)

Sponsors & Collaborators

• St Vincent's Hospital, Sydney: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (2)

St. Vincent's Hospital

Sydney, New South Wales, 2010, Australia

Location

The Alfred Hospital

Melbourne, Victoria, 3181, Australia

Location

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome

Interventions

Raltegravir Potassium

Condition Hierarchy (Ancestors)

HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Pyrrolidinones; Pyrrolidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Limitations and Caveats

Early termination leading to incomplete dataset with sample size too small to produce any meaningful statistical analysis.

Results Point of Contact

• Title: Prof. Bruce Brew
• Organization: St. Vincent's Hospital, Sydney

b.brew@unsw.edu.au

61 2 8382 1111

Study Officials

• Bruce J Brew, MBBS, PhD

  St Vincent's Hospital, Sydney

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: October 5, 2011
• First Posted: October 7, 2011
• Study Start: October 1, 2011
• Primary Completion: October 1, 2013
• Study Completion: October 1, 2013
• Last Updated: June 27, 2016
• Results First Posted: January 3, 2014

Record last verified: 2016-05

Locations

AU (2)