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

HIV Clinical Trial

— CHI  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04810858
• Other study ID #: IRB00098474
• Secondary ID: R01DA052827
• Status: Recruiting
• Phase: N/A
• Start date: August 18, 2021
• Est. completion date: May 31, 2025

Study information

• Verified date: May 2024
• Source: Wake Forest University Health Sciences
• Contact: Christina S Meade, PhD
• Phone: 336-716-0695
• Email: cmeade[@]wakehealth.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 220
• Est. completion date: May 31, 2025
• Est. primary completion date: May 31, 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 25 Years to 59 Years

Eligibility

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

Related Conditions & MeSH terms

• Cannabis
• Cognition
• HIV
• Inflammation
• Marijuana Use
• Neuroimaging

Intervention

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.
• 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.

Locations

Country	Name	City	State
United States	Biotech Place	Winston-Salem	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
Wake Forest University Health Sciences	National Institute on Drug Abuse (NIDA)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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