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

NCT ID: NCT01448486

Last Updated: 2016-06-27

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE4
• Total Enrollment: 6 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-10-31
• Study Completion Date: 2013-10-31

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)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Standard of Care HAART

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

Group Type: NO_INTERVENTION

No interventions assigned to this group

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).

Group Type: EXPERIMENTAL

Raltegravir

Intervention Type: DRUG

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

Interventions

Raltegravir

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

Intervention Type: DRUG

Other Intervention Names

Isentress

Eligibility 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)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: collaborator

St Vincent's Hospital, Sydney

OTHER

Sponsor Role: lead

Responsible Party

Bruce Brew

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Bruce J Brew, MBBS, PhD

Role: PRINCIPAL_INVESTIGATOR

St Vincent's Hospital, Sydney

Locations

St. Vincent's Hospital

Sydney, New South Wales, Australia

The Alfred Hospital

Melbourne, Victoria, Australia

Countries

Australia

Other Identifiers

IISP 37693

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

11/033

Identifier Type: -

Identifier Source: org_study_id