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

Study Overview
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Brief Summary
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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.

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

Conditions
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HIV, Cannabis, Inflammation, Cognition, Neuroimaging

Intervention / Treatment
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* Other: Multimodal, multi-parametric MRI
* Other: Immune and cytokine profiling
* Behavioral: Neuropsychological testing


Participation Criteria
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Eligibility Criteria
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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) 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

Ages Eligible for Study
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Minimum Age: 25 Years
Maximum Age: 59 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Participants will be assigned to one of 4 study groups: HIV+ marijuana user, HIV+ non-drug user, HIV- marijuana users, and HIV- non-drug user
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: HIV+ marijuana user<br>Participants with HIV who report marijuana use | Other: Multimodal, multi-parametric MRI<br>* The investigators will use multimodal, multi-parametric sequences to investigate neuroinflammatory and neurodegenerative processes in vivo. Participants will be assessed three times over 2 years.<br>Other: Immune and cytokine profiling<br>* Blood samples will be collected for immune and cytokine profiling. Participants will be assessed three times over 2 years.<br>Behavioral: Neuropsychological testing<br>* Participants will have neuropsychological testing three times over 2 years.<br>|
| Other: HIV+ non-drug user<br>Participants with HIV who report no drug use | Other: Multimodal, multi-parametric MRI<br>* The investigators will use multimodal, multi-parametric sequences to investigate neuroinflammatory and neurodegenerative processes in vivo. Participants will be assessed three times over 2 years.<br>Other: Immune and cytokine profiling<br>* Blood samples will be collected for immune and cytokine profiling. Participants will be assessed three times over 2 years.<br>Behavioral: Neuropsychological testing<br>* Participants will have neuropsychological testing three times over 2 years.<br>|
| Other: HIV- marijuana user<br>Participants without HIV who report marijuana use | Other: Multimodal, multi-parametric MRI<br>* The investigators will use multimodal, multi-parametric sequences to investigate neuroinflammatory and neurodegenerative processes in vivo. Participants will be assessed three times over 2 years.<br>Other: Immune and cytokine profiling<br>* Blood samples will be collected for immune and cytokine profiling. Participants will be assessed three times over 2 years.<br>Behavioral: Neuropsychological testing<br>* Participants will have neuropsychological testing three times over 2 years.<br>|
| Other: HIV- non-drug user<br>Participants without HIV who report no drug use | Other: Multimodal, multi-parametric MRI<br>* The investigators will use multimodal, multi-parametric sequences to investigate neuroinflammatory and neurodegenerative processes in vivo. Participants will be assessed three times over 2 years.<br>Other: Immune and cytokine profiling<br>* Blood samples will be collected for immune and cytokine profiling. Participants will be assessed three times over 2 years.<br>Behavioral: Neuropsychological testing<br>* Participants will have neuropsychological testing three times over 2 years.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in neurocognitive function as measured by neuropsychological battery | 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. | baseline, 1-year follow-up, and 2-year follow-up | 
| Change in neuronal integrity as measured by N-acetyl aspartate (NAA) | 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. | baseline, 1-year follow-up, and 2-year follow-up | 
| Change in neuronal-glial interaction as measured by Glutamate + glutamine (GLX) | 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. | baseline, 1-year follow-up, and 2-year follow-up | 
| Change in axonal loss and injury as measured by axonal diffusivity (AD) | 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. | baseline, 1-year follow-up, and 2-year follow-up | 
| Change in demyelination or dysmyelination as measured by radial diffusivity (RD) | 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. | baseline, 1-year follow-up, and 2-year follow-up | 
| Change in overall white matter integrity as measured by fractional anisotropy (FA) | 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. | baseline, 1-year follow-up, and 2-year follow-up | 
| Change in inflammation-related cellularity as measured by restricted fraction (RF) | 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. | baseline, 1-year follow-up, and 2-year follow-up | 
| Change in extracellular tissue edema as measured by non-restricted fraction (NF) | 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. | baseline, 1-year follow-up, and 2-year follow-up | 
| Change in gray matter as measured by cortical area and thickness and cortical and subcortical volume | 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. | baseline, 1-year follow-up, and 2-year follow-up | 
| Change in white matter integrity as measured by white matter tract streamline count | 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. | baseline, 1-year follow-up, and 2-year follow-up | 
| Change in axonal damage was measured by neurofilament light (NfL) protein | 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. | baseline, 1-year follow-up, and 2-year follow-up |