Modeling the Effects of Chronic Marijuana Use on Neuroinflammation and HIV-related Neuronal Injury

Not Applicable

Recruiting

• Conditions: HIV; Inflammation; Cognition; Neuroimaging; Cannabis
• Interventions: Other: Multimodal, multi-parametric MRI; Other: Immune and cytokine profiling; Behavioral: Neuropsychological testing

• Registration Number: NCT04810858
• Lead Sponsor: Wake Forest University Health Sciences

Brief Summary

This study applies a hypothesis-driven approach to examine the effects of chronic marijuana use on HIV-associated inflammation and its subsequent impacts on central nervous system function, with the goal of identifying the mechanisms through which cannabinoids modulate neurological disorders and other comorbidities in persons with HIV.

Detailed Description

Not available

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2021-03-16
• Study First Submitted QC: 2021-03-19
• Study First Posted: 2021-03-23
• Study Start: 2021-08-18
• Status Verified: 2024-05
• Last Update Submitted: 2024-05-29
• Last Update Posted: 2024-05-30
• Primary Completion: 2025-05-31
• Study Completion: 2025-05-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 220

Inclusion Criteria

• verified HIV status
• Current marijuana use (MJ+ groups only)
• No current marijuana use (MJ- groups only)
• current engagement in HIV care (HIV+ participants only)
• receipt of cART as first-line of treatment (HIV+ participants only)
• stable cART regimen (HIV+ participants only)
• undetectable HIV RNA viral load for >1 year (HIV+ participants only)

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Exclusion Criteria

• Lifetime abuse for any illicit drug other than marijuana
• <9th grade education; illiteracy or lack of fluency in English
• history of moderate or severe head trauma
• unstable or serious neurological disorders
• severe mental illness
• systemic autoimmune diseases
• immunotherapy
• MRI contraindications

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
HIV+ non-drug user	Neuropsychological testing	Participants with HIV who report no drug use
HIV- marijuana user	Neuropsychological testing	Participants without HIV who report marijuana use
HIV+ marijuana user	Immune and cytokine profiling	Participants with HIV who report marijuana use
HIV+ non-drug user	Immune and cytokine profiling	Participants with HIV who report no drug use
HIV+ marijuana user	Neuropsychological testing	Participants with HIV who report marijuana use
HIV- marijuana user	Immune and cytokine profiling	Participants without HIV who report marijuana use
HIV+ marijuana user	Multimodal, multi-parametric MRI	Participants with HIV who report marijuana use
HIV+ non-drug user	Multimodal, multi-parametric MRI	Participants with HIV who report no drug use
HIV- marijuana user	Multimodal, multi-parametric MRI	Participants without HIV who report marijuana use
HIV- non-drug user	Multimodal, multi-parametric MRI	Participants without HIV who report no drug use
HIV- non-drug user	Neuropsychological testing	Participants without HIV who report no drug use
HIV- non-drug user	Immune and cytokine profiling	Participants without HIV who report no drug use

Primary Outcome Measures

Name	Time	Method
Change in overall white matter integrity as measured by fractional anisotropy (FA)	baseline, 1-year follow-up, and 2-year follow-up	FA will be measured using diffusion-weighted imaging. Higher FA is associated with higher overall white matter integrity. FA is a scalar value between 0 and 1.
Change in axonal damage was measured by neurofilament light (NfL) protein	baseline, 1-year follow-up, and 2-year follow-up	NfL will be measured using blood serum and processed using an ultrasensitive immunoassay. Higher NfL is associated with more axonal damage. NfL protein units of measure are in picogram/milliliter\^-1.
Change in demyelination or dysmyelination as measured by radial diffusivity (RD)	baseline, 1-year follow-up, and 2-year follow-up	RD will be measured using diffusion-weighted imaging. Higher radial diffusivity is associated with more demyelination and dysmyelination. The unit of measure for RD is micrometer\^2/millisecond.
Change in extracellular tissue edema as measured by non-restricted fraction (NF)	baseline, 1-year follow-up, and 2-year follow-up	NF will be measured using diffusion-weighted imaging. Lower non-restricted fraction is associated with increased extracellular tissue edema. The unit of measure for NF is micrometer\^2/millisecond.
Change in white matter integrity as measured by white matter tract streamline count	baseline, 1-year follow-up, and 2-year follow-up	White matter tract streamline count will be measured using diffusion-weighted imaging. Lower white matter tract streamline count is associated with lower white matter integrity. The unit of measure for white matter tract streamline count is the total number of streamlines within a white matter tract.
Change in neurocognitive function as measured by neuropsychological battery	baseline, 1-year follow-up, and 2-year follow-up	The neuropsychological testing battery assesses 7 cognitive domains with 3-4 tests per domain. Raw scores from each test will be converted to demographically adjusted standard scores, called T-scores using up-to-date US normative data. A T-score of 50 is considered the normative mean, and each 10-point deviation is equivalent to 1 standard deviation. The minimum possible T-score is 0 and the maximum is 100, with higher scores meaning better neurocognitive function. The average T-score for all tests in a domain will be the domain T-score, and the average of all domain T-scores will be the global T-score. T-scores will serve as the primary continuous measure because they capture the full range of cognitive function.
Change in axonal loss and injury as measured by axonal diffusivity (AD)	baseline, 1-year follow-up, and 2-year follow-up	AD will be measured using diffusion-weighted imaging. Lower axonal diffusivity is associated with more axonal loss and injury. The unit of measure for AD is micrometer\^2/millisecond.
Change in inflammation-related cellularity as measured by restricted fraction (RF)	baseline, 1-year follow-up, and 2-year follow-up	RF will be measured using diffusion-weighted imaging. Higher restricted fraction is associated with higher inflammation-related cellularity. The unit of measure for RF is micrometer\^2/millisecond.
Change in gray matter as measured by cortical area and thickness and cortical and subcortical volume	baseline, 1-year follow-up, and 2-year follow-up	Cortical areas and thickness and cortical and subcortical volume will be measured using T1-weighted imaging. Lower gray matter is associated with decreased cognitive function and is a marker of neurodegenerative disease. Cortical area, thickness, and volume units of measure are in millimeter\^2. Subcortical volume units of measure are in millimeter\^3.
Change in neuronal integrity as measured by N-acetyl aspartate (NAA)	baseline, 1-year follow-up, and 2-year follow-up	NAA will be measured using Echo-planar spectroscopic imaging. Lower NAA is associated with less neuronal integrity. NAA units of measure is parts per million.
Change in neuronal-glial interaction as measured by Glutamate + glutamine (GLX)	baseline, 1-year follow-up, and 2-year follow-up	GLX will be measured using Echo-planar spectroscopic imaging. Lower GLX is indicative of less neuronal-glial interactions. GLX units of measure is parts per million.

Trial Locations

Locations (1)

Biotech Place; 🇺🇸 Winston-Salem, North Carolina, United States