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

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.

Study Overview

• Status: Recruiting
• Conditions: Inflammation; HIV; Cannabis; Cognition; Neuroimaging
• Intervention / Treatment: Other: Immune and cytokine profiling; Behavioral: Neuropsychological testing; Other: Multimodal, multi-parametric MRI

• Study Type: Interventional
• Enrollment (Estimated): 220
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Christina S Meade, PhD; Phone Number: 336-716-0695; Email: cmeade@wakehealth.edu
• Study Contact Backup: Name: Sheri L Towe, PhD; Phone Number: 336-716-4331; Email: stowe@wakehealth.edu

Study Locations

• United States
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27101
      • Recruiting
      • Biotech Place
      • Principal Investigator: Christina S Meade, PhD
      • Contact: Christina S Meade, PhD; Phone Number: 336-716-0695; Email: cmeade@wakehealth.edu
      • Contact: Sheri L Towe, PhD; Phone Number: 336-716-4331; Email: stowe@wakehealth.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 25 years to 59 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: HIV+ marijuana user; Participants with HIV who report marijuana use	Other: Immune and cytokine profiling; Blood samples will be collected for immune and cytokine profiling. Participants will be assessed three times over 2 years.; Behavioral: Neuropsychological testing; Participants will have neuropsychological testing three times over 2 years.; Other: Multimodal, multi-parametric MRI; 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.
Other: HIV+ non-drug user; Participants with HIV who report no drug use	Other: Immune and cytokine profiling; Blood samples will be collected for immune and cytokine profiling. Participants will be assessed three times over 2 years.; Behavioral: Neuropsychological testing; Participants will have neuropsychological testing three times over 2 years.; Other: Multimodal, multi-parametric MRI; 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.
Other: HIV- marijuana user; Participants without HIV who report marijuana use	Other: Immune and cytokine profiling; Blood samples will be collected for immune and cytokine profiling. Participants will be assessed three times over 2 years.; Behavioral: Neuropsychological testing; Participants will have neuropsychological testing three times over 2 years.; Other: Multimodal, multi-parametric MRI; 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.
Other: HIV- non-drug user; Participants without HIV who report no drug use	Other: Immune and cytokine profiling; Blood samples will be collected for immune and cytokine profiling. Participants will be assessed three times over 2 years.; Behavioral: Neuropsychological testing; Participants will have neuropsychological testing three times over 2 years.; Other: Multimodal, multi-parametric MRI; 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.

What is the study measuring?

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-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 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
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 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

Collaborators and Investigators

• Sponsor: Wake Forest University Health Sciences
• Collaborators: National Institute on Drug Abuse (NIDA)
• Investigators: Principal Investigator: Christina S Meade, PhD, Duke University

Study record dates

Study Major Dates

• Study Start (Actual): August 18, 2021
• Primary Completion (Estimated): May 31, 2025
• Study Completion (Estimated): May 31, 2025

Study Registration Dates

• First Submitted: March 16, 2021
• First Submitted That Met QC Criteria: March 19, 2021
• First Posted (Actual): March 23, 2021

Study Record Updates

• Last Update Posted (Actual): September 28, 2023
• Last Update Submitted That Met QC Criteria: September 26, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Nervous System Diseases; Substance-Related Disorders; Inflammation; Marijuana Use; Neuroinflammatory Diseases
• Other Study ID Numbers: IRB00098474; R01DA052827 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Any guidelines, protocols, and operating procedures generated will be made freely available. The investigators will make the data and associated documentation available to users under a data-sharing agreement.
• IPD Sharing 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.
• IPD Sharing 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.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No