Clinical trial NCT04920539: In Vivo Study of THC-induced Immune-genome Changes At Single Cell Solution in HIV-infected Humans
Official title: In Vivo Study of THC-induced Immune-genome Changes At Single Cell Solution in HIV-infected Humans
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: HIV Infections
Healthy
Lead sponsor: Yale University
Sponsor class: OTHER
Collaborators: name: National Institute on Drug Abuse (NIDA)
First posted: 2021-06-10
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

Brief summary: In this study, the investigators hypothesize that THC alters the immunogenome in a cell type-specific fashion and alters cytokine production via epigenetic regulatory mechanisms and that these alterations differ between HIV-infected and HIV-uninfected host genomes.

Detailed description: In this study, the investigators hypothesize that THC alters the immunogenome in a cell type-specific fashion and alters cytokine production via epigenetic regulatory mechanisms and that these alterations differ between HIV-infected and HIV-uninfected host genomes. To test these hypotheses, the investigators propose defining the epigenomic and transcriptomic alterations at single cell resolution in peripheral blood mononuclear cells by administering THC to humans with and without HIV infection. The THC-associated epigenomic/transcriptomic alterations will be linked to genomic variants to understand the causal effects of THC response in immune cells.

Eligibility criteria: Inclusion Criteria (HIV-infected group):

* HIV-positive
* Good medication adherence
* Negative urine toxicology for drugs of abuse (including cannabis)
* Good mental and physical health (other than HIV) as determined by history, psychiatric interview, collateral information, physical and laboratory examinations, ECG, and vital signs.

Inclusion Criteria (HIV-uninfected group):

* HIV-negative
* Negative urine toxicology for drugs of abuse (including cannabis)
* Good mental and physical health as determined by history, psychiatric interview, collateral information, physical and laboratory examinations, ECG, and vital signs.

Exclusion Criteria (common to both groups):

* Major medical conditions, e.g., myocardial infarction, hypertension, etc.
* Positive pregnancy test and lactation;
* Weight greater than 166 kg (365 lbs)

Primary outcomes:
measure: Change in Gene Expression Alteration
timeFrame: Blood samples will be collected to measure changes in gene expression altered by THC before study drug infusion and at 70, 140, and 300 minutes after study drug infusion.
measure: Change in Cytokine Profile
timeFrame: Blood samples will be collected to measure changes in cytokine profile before study drug infusion and at 70, 140, and 300 minutes after study drug infusion.
measure: Change in Gene Expression Alteration by THC between HIV-positive and HIV-negative Groups
timeFrame: Blood samples will be collected to measure change in gene expression altered by THC before study drug infusion and at 70, 140, and 300 minutes after study drug infusion.
measure: Change in Cytokine Profile by THC between HIV-positive and HIV-negative Groups
timeFrame: Blood samples will be collected to measure changes in cytokine profile by THC before study drug infusion and at 70, 140, and 300 minutes after study drug infusion.
Secondary outcomes:
measure: Perceptual Alterations
timeFrame: Perceptual alterations will be measured before study drug infusion and 70, 140, and 300 minutes after study drug infusion.
measure: Cannabis Subjective Effects
timeFrame: Cannabis subjective effects will be measured before study drug infusion and 70, 140, and 300 minutes after study drug infusion.
measure: Cannabinoid Relevant Molecules
timeFrame: Blood will be collected before study drug infusion and at 70, 140, and 300 minutes after study drug infusion.
measure: Change in total immediate recall on the RAVLT.
timeFrame: The RAVLT will be administered prior to study drug administration at approximately 25 minutes after study drug administration.
Other outcomes:
Locations:
city: West Haven
country: United States
facility: VA Connecticut Healthcare System
state: Connecticut
Study officials:
affiliation: Yale University Professor of Psychiatry
name: Deepak C D'Souza, MD
role: PRINCIPAL_INVESTIGATOR
References: