Clinical trial NCT01929759: Advanced Neuroimaging Evaluation of the Central Nervous System Biological Changes Associated With Efavirenz Therapy and Switch to an Elvitegravir-based Regimen
Official title: Advanced Neuroimaging Evaluation of the Central Nervous System Biological Changes Associated With Efavirenz Therapy and Switch to an Elvitegravir-based Regimen
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: HIV Disease
Keywords: HIV
neurocognitive symptoms
efavirenz
elvitegravir
neurometabolites
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
Collaborators: name: Brigham and Women's Hospital
name: Gilead Sciences
First posted: 2013-08-28
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Treatment switch study
Primary purpose: BASIC_SCIENCE

Brief summary: 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.


Eligibility criteria: 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 - 65

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.

Primary outcomes:
measure: Change in Neurometabolites Based on Magnetic Resonance Spectroscopy (MRS)
timeFrame: week 0 to week 8
measure: Neural Activation Networks Using Functional Magnetic Resonance Imaging (fMRI)
timeFrame: week 0 and week 8
Secondary outcomes:
measure: Change in Other Neurometabolite Measured by MRS Between Week 0 and Week 8
timeFrame: week 0 to week 8
measure: Neurocognitive Changes
timeFrame: week 0 and week 8
measure: Fasting Lipid Profile
timeFrame: 8 weeks
measure: Sleep Quality
timeFrame: week 0 and week 8
measure: ART Regimen Preference
timeFrame: week 0 and week 8
measure: Markers of Immune Activation
timeFrame: week 0 and week 8
measure: Effect of EFV and Its Metabolites
timeFrame: week 0 and week 8
Other outcomes:
Locations:
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
Study officials:
References: