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

NCT04810858 | Recruiting

• 2 other identifiers: IRB00098474R01DA052827
• Study Type: interventional
• Target: 220
• Locations: 1 country
• Sites: 1

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.

Conditions

Cannabis; HIV; Inflammation; Cognition; Neuroimaging

Outcome Measures

Primary Outcomes (11)

• 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

Study Arms (4)

HIV+ marijuana user

OTHER

Participants with HIV who report marijuana use

Other: Multimodal, multi-parametric MRI; Other: Immune and cytokine profiling; Behavioral: Neuropsychological testing

HIV+ non-drug user

OTHER

Participants with HIV who report no drug use

Other: Multimodal, multi-parametric MRI; Other: Immune and cytokine profiling; Behavioral: Neuropsychological testing

HIV- marijuana user

OTHER

Participants without HIV who report marijuana use

Other: Multimodal, multi-parametric MRI; Other: Immune and cytokine profiling; Behavioral: Neuropsychological testing

HIV- non-drug user

OTHER

Participants without HIV who report no drug use

Other: Multimodal, multi-parametric MRI; Other: Immune and cytokine profiling; Behavioral: Neuropsychological testing

Interventions

Multimodal, multi-parametric MRI OTHER

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.

HIV+ marijuana user; HIV+ non-drug user; HIV- marijuana user; HIV- non-drug user

Immune and cytokine profiling OTHER

Blood samples will be collected for immune and cytokine profiling. Participants will be assessed three times over 2 years.

HIV+ marijuana user; HIV+ non-drug user; HIV- marijuana user; HIV- non-drug user

Neuropsychological testing BEHAVIORAL

Participants will have neuropsychological testing three times over 2 years.

HIV+ marijuana user; HIV+ non-drug user; HIV- marijuana user; HIV- non-drug user

Eligibility Criteria

• Age: 25 Years - 59 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Wake Forest University Health Sciences: lead
• National Institute on Drug Abuse (NIDA): collaborator

Study Sites (1)

Biotech Place

Winston-Salem, North Carolina, 27101, United States

RECRUITING

MeSH Terms

Conditions

Marijuana Abuse; Inflammation

Interventions

Neuropsychological Tests

Condition Hierarchy (Ancestors)

Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Psychological Tests; Behavioral Disciplines and Activities

Study Officials

• Christina S Meade, PhD

  Wake Forest University Health Sciences

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Christina S Meade, PhD

CONTACT

336-716-0695; Christina.Meade@wfusm.edu

Sheri L Towe, PhD

CONTACT

336-716-4331; Sheri.Towe@wfusm.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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

Study Record Dates

• First Submitted: March 16, 2021
• First Posted: March 23, 2021
• Study Start: August 18, 2021
• Primary Completion (Estimated): May 31, 2027
• Study Completion (Estimated): May 31, 2027
• Last Updated: March 31, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: The investigators will lock the data until the primary analyses are completed and accepted for publication, after which the investigators will make the data as widely available as possible.
• Access Criteria: Data sharing agreements will include: (1) a commitment to acknowledge the sources of the data and conform to the terms and conditions under which they accessed it, (2) a commitment to use the data only for research purposes and not to identify any individual participant, (3) a commitment to securing the data using appropriate computer technology, and (4) a commitment to destroying or returning the data after analyses are completed.

Locations

US (1)