Advanced Neuroimaging Evaluation of the Central Nervous System Biological Changes Associated With Efavirenz Therapy and Switch to an Elvitegravir-based Regimen

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified August 2013 by Massachusetts General Hospital
Sponsor:
Collaborators:
Brigham and Women's Hospital
Gilead Sciences
Information provided by (Responsible Party):
Nina Lin, MD, Massachusetts General Hospital
ClinicalTrials.gov Identifier:
NCT01929759
First received: August 23, 2013
Last updated: August 27, 2013
Last verified: August 2013

August 23, 2013
August 27, 2013
October 2013
May 2014   (final data collection date for primary outcome measure)
  • Neurometabolites based on MRS [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    Assess the changes in levels of neuro-metabolites measured by MRS while on and off the efavirenz-based therapy. Two areas of the brain; 1) posterior cingulate gyrus and 2) anterior cingulate will be assessed for change in levels of brain Cr, GABA and GLU between week 0 and 8 of switch to an elvitegravir-based regimen.
  • Neural activation networks using fMRI [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    Assess changes in neural activation correlated with affective disturbances associated with efavirenz-based therapy using fMRI employing a paradigm that probes affective symptomatologies typical with EFV use, specifically anxiety/dysphoria and affective dysregulation and their association with changes in cognitive function.
Same as current
Complete list of historical versions of study NCT01929759 on ClinicalTrials.gov Archive Site
  • Other neurometabolite changes measured by MRS [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    Use MRS to evaluate a fuller panel of known neurometabolites (in addition to the primary endpoints) to evaluate for prominent and significant changes associated with EFV use.
  • Neurocognitive changes [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    Assess for changes in cognitive and affective function prior to and after switching off EFV-based regimen.
  • Fasting lipid profile [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    Measure the change in fasting lipid panel prior to and after switching off EFV-based regimen.
  • Sleep quality [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    Assess for changes in sleep pattern and quality prior to and after switching off EFV-based regimen through self-administered questionnaires.
  • ART regimen preference [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    Evaluate patient preference in ART regimen (Atripla, EFV/FTC/TDF versus EVG/COBI/FTC/TDF) through self-administered questionnaires.
  • Markers of immune activation [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    Change in markers of immune activation and inflammation associated with change to RAL (ie, sCD14, IL-6, hsCRP, D-dimer, CRP, LPS, sCD163, EndoCab)
Same as current
Not Provided
Not Provided
 
Advanced Neuroimaging Evaluation of the Central Nervous System Biological Changes Associated With Efavirenz Therapy and Switch to an Elvitegravir-based Regimen
Advanced Neuroimaging Evaluation of the Central Nervous System Biological Changes Associated With Efavirenz Therapy and Switch to an Elvitegravir-based Regimen

In this study we 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. In a cohort of HIV-infected patients who are clinically stable on the commonly use regimen of EFV/emtricitabine (FTC)/truvada (TDF) or Atripla, we propose to replace the EFV component with a new integrase inhibitor, elvitegravir (EVG) boosted with cobicistat (COBI), given as the EVG/COBI/FTC/TDF Single Tablet Regimen (STR) to evaluate the EFV-related neural alterations. This is a multidisciplinary study which involves a team of infectious disease experts in the field of HIV, neuroradiologists with expertise in fMRI and MRS techniques to study various central nervous system and psychiatric disorders and a psychiatrist with experience and expertise in research on abnormalities of affective and motivational processing in the context of neuropsychiatric disorders. We will utilize the established clinical research platform in the Infectious Disease outpatient clinical practice at the Brigham and Women's Hospital, where there is currently have many ongoing HIV-related studies and a large panel of HIV-infected patients motivated to be involved in clinically relevant research. We propose to use advanced neuroimaging to measure biologically changes in the brain associated with long-term EFV use with the following specific aims:

  1. Determine changes in neurometabolites measured by MRS in the brain associated with long-term EFV use
  2. Assess for alterations in neural activity correlated with affective symptoms associated with EFV vs STR use using fMRI, and their associations with changes in neurometabolites assessed by MRS, and with changes in cognition assessed by Trail Making and Digit Substitution Tests.
  3. Determine changes in emotion, cognition and sleep quality after switching from EFV to STR, and how they correlate with subject treatment preference.

This clinical study will extend our current understanding of EFV neurotoxicity by further defining the nature of these biological changes. Further elucidation of the neurobiological underpinnings of EFV-induced CNS toxicity will have clinical relevance in improving the quality of life and drug adherence of HIV-infected patients on ART, especially among older patients or those with baseline neuropsychiatric disorders, whom at baseline are more vulnerable to neurocognitive decline from long-term HIV infection.

Not Provided
Interventional
Not Provided
Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Basic Science
HIV Disease
Drug: Stribild (elvitegravir, cobicistat, emtricitabine and tenofovir)
Switch from Atripla (efavirenz, emtricitabine and tenofovir) to Stribild (elvitegravir, cobicistat, emtricitabine and tenofovir)for total of 8 weeks
Drug switching
Single-arm with switch from baseline antiretroviral therapy with Atripla to Stribild for total of 8 weeks.
Intervention: Drug: Stribild (elvitegravir, cobicistat, emtricitabine and tenofovir)
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Not yet recruiting
10
October 2014
May 2014   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • 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 - 75

Exclusion Criteria:

  • 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.
Both
18 Years to 75 Years
No
Contact: Nina Lin, MD 617-768-8479 nhlin@partners.org
United States
 
NCT01929759
NeuroHIV001
No
Nina Lin, MD, Massachusetts General Hospital
Massachusetts General Hospital
  • Brigham and Women's Hospital
  • Gilead Sciences
Not Provided
Massachusetts General Hospital
August 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP