Back to resultsModeling the Effects of Chronic Marijuana Use on Neuroinflammation and HIV-related Neuronal Injury (CHI)
Primary Purpose
Cannabis, HIV, Inflammation
Status
Recruiting
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Multimodal, multi-parametric MRI
Immune and cytokine profiling
Neuropsychological testing
Sponsored by
About this trial
This is an interventional basic science trial for Cannabis
Eligibility 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
Sites / Locations
- Biotech PlaceRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Other
Other
Other
Other
Arm Label
HIV+ marijuana user
HIV+ non-drug user
HIV- marijuana user
HIV- non-drug user
Arm Description
Participants with HIV who report marijuana use
Participants with HIV who report no drug use
Participants without HIV who report marijuana use
Participants without HIV who report no drug use
Outcomes
Primary Outcome Measures
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Secondary Outcome Measures
Full Information
NCT ID
NCT04810858
First Posted
March 16, 2021
Last Updated
September 26, 2023
Sponsor
Wake Forest University Health Sciences
Collaborators
National Institute on Drug Abuse (NIDA)
1. Study Identification
Unique Protocol Identification Number
NCT04810858
Brief Title
Modeling the Effects of Chronic Marijuana Use on Neuroinflammation and HIV-related Neuronal Injury
Acronym
CHI
Official Title
Modeling the Effects of Chronic Marijuana Use on Neuroinflammation and HIV-related Neuronal Injury
Study Type
Interventional
2. Study Status
Record Verification Date
June 2023
Overall Recruitment Status
Recruiting
Study Start Date
August 18, 2021 (Actual)
Primary Completion Date
May 31, 2025 (Anticipated)
Study Completion Date
May 31, 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Wake Forest University Health Sciences
Collaborators
National Institute on Drug Abuse (NIDA)
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cannabis, HIV, Inflammation, Cognition, Neuroimaging
7. Study Design
Primary Purpose
Basic Science
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
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)
Allocation
Non-Randomized
Enrollment
220 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
HIV+ marijuana user
Arm Type
Other
Arm Description
Participants with HIV who report marijuana use
Arm Title
HIV+ non-drug user
Arm Type
Other
Arm Description
Participants with HIV who report no drug use
Arm Title
HIV- marijuana user
Arm Type
Other
Arm Description
Participants without HIV who report marijuana use
Arm Title
HIV- non-drug user
Arm Type
Other
Arm Description
Participants without HIV who report no drug use
Intervention Type
Other
Intervention Name(s)
Multimodal, multi-parametric MRI
Intervention Description
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.
Intervention Type
Other
Intervention Name(s)
Immune and cytokine profiling
Intervention Description
Blood samples will be collected for immune and cytokine profiling. Participants will be assessed three times over 2 years.
Intervention Type
Behavioral
Intervention Name(s)
Neuropsychological testing
Intervention Description
Participants will have neuropsychological testing three times over 2 years.
Primary Outcome Measure Information:
Title
Change in neurocognitive function as measured by neuropsychological battery
Description
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.
Time Frame
baseline, 1-year follow-up, and 2-year follow-up
Title
Change in neuronal integrity as measured by N-acetyl aspartate (NAA)
Description
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.
Time Frame
baseline, 1-year follow-up, and 2-year follow-up
Title
Change in neuronal-glial interaction as measured by Glutamate + glutamine (GLX)
Description
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.
Time Frame
baseline, 1-year follow-up, and 2-year follow-up
Title
Change in axonal loss and injury as measured by axonal diffusivity (AD)
Description
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.
Time Frame
baseline, 1-year follow-up, and 2-year follow-up
Title
Change in demyelination or dysmyelination as measured by radial diffusivity (RD)
Description
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.
Time Frame
baseline, 1-year follow-up, and 2-year follow-up
Title
Change in overall white matter integrity as measured by fractional anisotropy (FA)
Description
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.
Time Frame
baseline, 1-year follow-up, and 2-year follow-up
Title
Change in inflammation-related cellularity as measured by restricted fraction (RF)
Description
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.
Time Frame
baseline, 1-year follow-up, and 2-year follow-up
Title
Change in extracellular tissue edema as measured by non-restricted fraction (NF)
Description
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.
Time Frame
baseline, 1-year follow-up, and 2-year follow-up
Title
Change in gray matter as measured by cortical area and thickness and cortical and subcortical volume
Description
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.
Time Frame
baseline, 1-year follow-up, and 2-year follow-up
Title
Change in white matter integrity as measured by white matter tract streamline count
Description
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.
Time Frame
baseline, 1-year follow-up, and 2-year follow-up
Title
Change in axonal damage was measured by neurofilament light (NfL) protein
Description
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.
Time Frame
baseline, 1-year follow-up, and 2-year follow-up
10. Eligibility
Sex
All
Minimum Age & Unit of Time
25 Years
Maximum Age & Unit of Time
59 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Christina S Meade, PhD
Phone
336-716-0695
Email
cmeade@wakehealth.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Sheri L Towe, PhD
Phone
336-716-4331
Email
stowe@wakehealth.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Christina S Meade, PhD
Organizational Affiliation
Duke University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Biotech Place
City
Winston-Salem
State/Province
North Carolina
ZIP/Postal Code
27101
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Christina S Meade, PhD
Phone
336-716-0695
Email
cmeade@wakehealth.edu
First Name & Middle Initial & Last Name & Degree
Sheri L Towe, PhD
Phone
336-716-4331
Email
stowe@wakehealth.edu
First Name & Middle Initial & Last Name & Degree
Christina S Meade, PhD
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing 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.
Learn more about this trial
Modeling the Effects of Chronic Marijuana Use on Neuroinflammation and HIV-related Neuronal Injury
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