Advanced Neuroimaging Evaluation of CNS Changes Associated With Efavirenz Therapy Switch to an Raltegravir-based Regimen

NCT01978743 | Completed Results

• 1 other identifier: NeuroHIV002
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

In this study investigators will use a multi-modal imaging approach of MRS and fMRI to comprehensively assess the biological changes in the brain associated with EFV-based regimen (EFV/FTC/TDF), specifically alterations in the brain circuitry, function and local neurochemistry, and their correlation with neuropsychological function.

Conditions

HIV; HIV-associated Neurocognitive Disorder; Neurotoxicity

Keywords

HIV; HIV-associated neurocognitive disorder; neurotoxicity

Outcome Measures

Primary Outcomes (2)

• Neurometabolites Based on Magnetic Resonance Spectroscopy (MRS)

  Assess the levels of neuro-metabolites measured by MRS at week 0 before switching to the efavirenz-based therapy. Two areas of the brain: 1) posterior cingulate gyrus and 2) anterior cingulate will be assessed for the levels of brain creatine (Cr), gamma-aminobutyric acid (GABA) and glutathione (GLU).

  week 0 and week 8

• Neural Activation Networks Using Functional Magnetic Resonance Imaging (fMRI)

  Assess changes in neural activation correlated with affective disturbances associated with EFV vs. RAL using fMRI employing a paradigm that probes affective symptomatologies typical with EFV use; anxiety/dysphoria and affective dysregulation, and their association with changes in cognitive function. Four brain regions of interests (ROIs) are specified to show the differential frontal-limbic activation patterns in the task-evoked neural responses to the 3 linear contrasts of Pre-/Post-/ Pre-vs. Post-switch: \[Negative Word vs. Neutral Word\] x \[No-Go Trial Block vs. Go Trial Block\]: anterior Frontal Pole (aFP), posterior Cingulate Gyrus (pCG), dorsal anterior Cingulate Gyrus (daCG), Left Hippocampus (LHC). A linear mixed-effects model is utilized to examine the effect sizes of the key Regimen/Condition contrasts, with the Subject factor as the random-effect, and Age incorporated as a co-variate of no interest. A z-score is the Mean with a SD=1 and Measure of Dispersion equal to 1.

  week 0 and week 8

Secondary Outcomes (7)

• Other Neurometabolite Changes Measured by MRS

  week 0 and week 8

• Neurocognitive Changes Measured by a Panel of Indexes: WAIS-R, HAMD, DASS-21, FRSBE, STAI

  week 0 and week 8

• Fasting Lipid Profile

  week 0 and week 8

• Sleep Quality

  week 0 and week 8

• ART Regimen Preference

  week 0 and week 8

Study Arms (1)

Raltegravir

EXPERIMENTAL

Switch from Atripla (EFV/FTC/TDF) to raltegravir (RAL) + Truvada (FTC/TDF). Raltegravir will be administered 400mg twice-a-day with Truvada for 8 weeks.

Drug: Raltegravir

Interventions

Raltegravir DRUG

Switch from Atripla to Raltegravir 400mg BID + Truvada (FTC/TDF) for total of 8 weeks

Also known as: Raltegravir (Isentress) 400mg BID

Raltegravir

Eligibility Criteria

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

You may qualify if:

• Chronic HIV-infected individuals on suppressive regimen with EFV/FTC/TDF, for at least 6 months
• Undetectable HIV-1 RNA virus load for at least 6 months
• No co-infections with active hepatitis B and C
• Presence of at least moderate symptoms on 2 out of 3 subcores on the DASS
• No known active HIV-related and non-HIV related CNS infections
• Estimated glomerular filtration rate (EGFR) \>60 ml/min
• Consent to switching to EVG/COBI/FTC/TDF
• Ages 18 - 65

You may not qualify if:

• History of CNS opportunistic infections or active CNS infections
• History of severe psychiatric disorder (excluding depression and anxiety)
• History of chronic neurological disorders, such as epilepsy or multiple sclerosis
• History of or current significant substance abuse or dependence and/or heavy alcohol use (\>12 oz/wk)
• Any women who may be pregnant (positive urine pregnancy test or unprotected sex in 2 weeks prior to scan) or known to be pregnant
• Contraindications to undergoing fMRI, including metallic implants, claustrophobia, and medical conditions or medications that significantly affect cerebral blood flow or function.

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

Brigham and Women's hospital

Boston, Massachusetts, 02115, United States

Location

MeSH Terms

Conditions

Neurotoxicity Syndromes

Interventions

Raltegravir Potassium; BID protein, human

Condition Hierarchy (Ancestors)

Nervous System Diseases; Poisoning; Chemically-Induced Disorders

Intervention Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Dr. Nina Lin
• Organization: Boston University School of Medicine

nina.lin@bmc.org

617-414-5242

Study Officials

• Nina Lin, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor in Medicine

Study Record Dates

• First Submitted: October 20, 2013
• First Posted: November 7, 2013
• Study Start: January 1, 2014
• Primary Completion: September 1, 2016
• Study Completion: January 1, 2017
• Last Updated: July 26, 2017
• Results First Posted: July 26, 2017

Record last verified: 2017-07

Locations

US (1)