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

Human Immunodeficiency Virus (HIV) Clinical Trial

— HANDral  

Official title:

A Randomised Controlled Clinical Trial of the Efficacy of HAART Intensification With Raltegravir in HIV Virally Suppressed Patients With Cognitive Impairment

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01448486
• Other study ID #: 11/033
• Secondary ID: IISP 37693
• Status: Terminated
• Phase: Phase 4
• First received: October 5, 2011
• Last updated: November 13, 2013
• Start date: October 2011
• Est. completion date: October 2013

Study information

• Verified date: November 2013
• Source: St Vincent's Hospital, Sydney
• Contact: n/a
• Is FDA regulated: No
• Health authority: Australia: Human Research Ethics CommitteeAustralia: Department of Health and Ageing Therapeutic Goods Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 6
• Est. completion date: October 2013
• Est. primary completion date: October 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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)

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Acquired Immunodeficiency Syndrome
• HIV Associated Neurocognitive Disorders (HAND)
• HIV Infections
• Human Immunodeficiency Virus (HIV)
• Immunologic Deficiency Syndromes

Intervention

Drug:
• Raltegravir
Oral raltegravir, 400 mg tablet, twice daily for one year.

Locations

Country	Name	City	State
Australia	The Alfred Hospital	Melbourne	Victoria
Australia	St. Vincent's Hospital	Sydney	New South Wales

Sponsors (2)

Lead Sponsor	Collaborator
St Vincent's Hospital, Sydney	Merck Sharp & Dohme Corp.

Country where clinical trial is conducted

Australia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Neurocognitive Function	The primary endpoint is improvement on overall neuropsychological performance defined as a reliable change score index (RCI) corrected for practice effect.	Change from baseline neuropsychological testing, at 6 months, and at 12 months	No
Secondary	Cerebrospinal Fluid	To determine if there is improvement in CSF neopterin concentrations with the addition of Raltegravir.	Change in Neopterin concentrations in CSF from baseline to 12 months	No