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

• ClinicalTrials.gov Identifier: NCT04810858
• Recruitment Status: Recruiting
• First Posted: March 23, 2021
• Last Update Posted: August 23, 2021
• Sponsor: Duke University
• Collaborator: National Institute on Drug Abuse (NIDA)
• Information provided by (Responsible Party): Duke University

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Cannabis; HIV; Inflammation; Cognition; Neuroimaging	Device: Multimodal, multi-parametric MRI; Other: Immune and cytokine profiling; Behavioral: Neuropsychological testing	Not Applicable

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 220 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Intervention 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)
• Primary Purpose: Basic Science
• Official Title: Modeling the Effects of Chronic Marijuana Use on Neuroinflammation and HIV-related Neuronal Injury
• Actual Study Start Date: August 18, 2021
• Estimated Primary Completion Date: May 31, 2025
• Estimated Study Completion Date: May 31, 2025

Arms and Interventions

Arm	Intervention/treatment
HIV+ marijuana user; Participants with HIV who report marijuana use	Device: 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: 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.
HIV+ non-drug user; Participants with HIV who report no drug use	Device: 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: 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.
HIV- marijuana user; Participants without HIV who report marijuana use	Device: 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: 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.
HIV- non-drug user; Participants without HIV who report no drug use	Device: 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: 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.

Outcome Measures

Primary Outcome Measures :

1. Change in neurocognitive function as measured by neuropsychological battery [ Time Frame: 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.
2. Change in neuronal integrity as measured by N-acteyl aspartate (NAA) [ Time Frame: 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.
3. Change in neuronal-glial interaction as measured by Glutamate + glutamine (GLX) [ Time Frame: 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.
4. Change in axonal loss and injury as measured by axonal diffusivity (AD) [ Time Frame: 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.
5. Change in demyelination or dysmyelination as measured by radial diffusivity (RD) [ Time Frame: 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 demylination and dysmyelination. The unit of measure for RD is micrometer^2/millisecond.
6. Change in overall white matter integrity as measured by fractional anisotropy (FA) [ Time Frame: 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.
7. Change in inflammation-related cellularity as measured by restricted fraction (RF) [ Time Frame: 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.
8. Change in extracellular tissue edema as measured by non-restricted fraction (NF) [ Time Frame: 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.
9. Change in gray matter as measured by cortical area and thickness and cortical and subcortical volume [ Time Frame: 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.
10. Change in white matter integrity as measured by white matter tract streamline count [ Time Frame: 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.
11. Change in axonal damage was measured by neurofilament light (NfL) protein [ Time Frame: 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.

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Contacts

Contact: Christina S Meade, PhD; 919-613-6549; christina.meade@duke.edu

Contact: Sheri L Towe, PhD; 919-668-4030; sheri.towe@duke.edu

Locations

United States, North Carolina

Duke University Medical Center; Recruiting

Durham, North Carolina, United States, 27710

Contact: Christina S Meade, PhD 919-613-6549 christina.meade@duke.edu

Contact: Sheri L Towe, PhD 919-668-4030 sheri.towe@duke.edu

Principal Investigator: Christina S Meade, PhD

Sponsors and Collaborators

Duke University

National Institute on Drug Abuse (NIDA)

Investigators

• Principal Investigator: Christina S Meade, PhD; Duke University

More Information

• Responsible Party: Duke University
• ClinicalTrials.gov Identifier: NCT04810858
• Other Study ID Numbers: Pro00106797; R01DA052827 ( U.S. NIH Grant/Contract )
• First Posted: March 23, 2021
• Last Update Posted: August 23, 2021
• Last Verified: August 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• 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.
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (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.

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Inflammation; Marijuana Use; Pathologic Processes; Substance-Related Disorders; Mental Disorders