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In Vivo Study of THC-induced Immune-genome Changes at Single Cell Solution in HIV-infected Humans

Primary Purpose

HIV Infections, Healthy

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Active Delta-9-THC
Sponsored by
Yale University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional other trial for HIV Infections

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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)

Sites / Locations

  • VA Connecticut Healthcare SystemRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Active Delta-9-THC

Arm Description

Active Delta-9-THC (0.03 mg/kg) administered intravenously.

Outcomes

Primary Outcome Measures

Change in Gene Expression Alteration
Quantity of each gene is measured via sequence transcriptome, and significant differences of quantified gene pre- and post-THC infusion will be identified as THC-induced gene expression alteration.
Change in Cytokine Profile
Cytokine profile will be measured using Luminex Performance Human Cytokine Discovery panel before and after study drug infusion. The 45 cytokines selected based on their established role in immune functioning are: CCL2/MCP-1, CCL3/MIP-1a, CCL4/MIP-1b, CCL5/RANTES, CCL11/Eotaxin, CCL19/MIP-3b, CCL20/MIP-3a, TNFSF5, CX3CL1/Fractalkine, CXCL1/GROa, CXCL2/GROb, CXCL10/IP-10, EGF, FGF2, FLT3L, G-CSF, GM-CSF, Granzyme B, IFN-a2, IFN-b, IFN-g, IL-1a, IL-1b, IL-1ra, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IL-8/CXCL8, IL-10, IL-12 p70, IL-13, IL-15, IL-17A, IL-17E, IL-33, PD-L1, PDGF-AA, PDGF-AB/BB, TGF-a, TNF-a, TNFSF10, VEGF.
Change in Gene Expression Alteration by THC between HIV-positive and HIV-negative Groups
Quantity of each gene is measured via sequence transcriptome, and significant differences of quantified gene pre- and post-THC infusion are identified as THC-induced gene expression alteration. Results will be compared between HIV-positive and HIV-negative subjects.
Change in Cytokine Profile by THC between HIV-positive and HIV-negative Groups
Cytokine profile will be measured using Luminex Performance Human Cytokine Discovery panel before and after study drug infusion. Results will be compared between HIV-positive and HIV-negative subjects. The 45 cytokines selected based on their established role in immune functioning are: CCL2/MCP-1, CCL3/MIP-1a, CCL4/MIP-1b, CCL5/RANTES, CCL11/Eotaxin, CCL19/MIP-3b, CCL20/MIP-3a, TNFSF5, CX3CL1/Fractalkine, CXCL1/GROa, CXCL2/GROb, CXCL10/IP-10, EGF, FGF2, FLT3L, G-CSF, GM-CSF, Granzyme B, IFN-a2, IFN-b, IFN-g, IL-1a, IL-1b, IL-1ra, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IL-8/CXCL8, IL-10, IL-12 p70, IL-13, IL-15, IL-17A, IL-17E, IL-33, PD-L1, PDGF-AA, PDGF-AB/BB, TGF-a, TNF-a, TNFSF10, VEGF.

Secondary Outcome Measures

Perceptual Alterations
Perceptual alterations will be measured using scales such as the Clinician Administered Dissociative Symptoms Scale (CADSS), a scale consisting of 19 self-report items and 8 clinician-rated items (0 = not at all, 4 = extremely) that we have shown to be sensitive to THC effects. The scale captures alterations in environmental/time/body perception, feelings of unreality, and memory impairment.
Cannabis Subjective Effects
Various feeling states associated with cannabis intoxication will be measured using a self-reported visual analog scale of feeling states ("high", "calm and relaxed", and "tired") associated with cannabis effects. Subjects will be asked to score the perceived intensity of these feeling states at that moment on a 100 mm line (0 = not at all, 100 = extremely). These data will be captured to validate that the experiment is relevant to cannabis effects.
Cannabinoid Relevant Molecules
Blood will be sampled for cannabinoid relevant molecules before and after study drug infusion. Cannabinoid relevant molecules will include THC and THC-COOH levels.
Change in total immediate recall on the RAVLT.
Memory, attention, and executive function will be measured before and after study drug administration using the Rey Auditory Verbal Learning Task (RAVLT).

Full Information

First Posted
May 17, 2021
Last Updated
March 17, 2023
Sponsor
Yale University
Collaborators
National Institute on Drug Abuse (NIDA)
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1. Study Identification

Unique Protocol Identification Number
NCT04920539
Brief Title
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

2. Study Status

Record Verification Date
March 2023
Overall Recruitment Status
Recruiting
Study Start Date
February 8, 2022 (Actual)
Primary Completion Date
June 30, 2025 (Anticipated)
Study Completion Date
June 30, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Yale University
Collaborators
National Institute on Drug Abuse (NIDA)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HIV Infections, Healthy

7. Study Design

Primary Purpose
Other
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
40 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Active Delta-9-THC
Arm Type
Experimental
Arm Description
Active Delta-9-THC (0.03 mg/kg) administered intravenously.
Intervention Type
Drug
Intervention Name(s)
Active Delta-9-THC
Intervention Description
Active Delta-9-THC (0.03 mg/kg) administered intravenously.
Primary Outcome Measure Information:
Title
Change in Gene Expression Alteration
Description
Quantity of each gene is measured via sequence transcriptome, and significant differences of quantified gene pre- and post-THC infusion will be identified as THC-induced gene expression alteration.
Time Frame
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.
Title
Change in Cytokine Profile
Description
Cytokine profile will be measured using Luminex Performance Human Cytokine Discovery panel before and after study drug infusion. The 45 cytokines selected based on their established role in immune functioning are: CCL2/MCP-1, CCL3/MIP-1a, CCL4/MIP-1b, CCL5/RANTES, CCL11/Eotaxin, CCL19/MIP-3b, CCL20/MIP-3a, TNFSF5, CX3CL1/Fractalkine, CXCL1/GROa, CXCL2/GROb, CXCL10/IP-10, EGF, FGF2, FLT3L, G-CSF, GM-CSF, Granzyme B, IFN-a2, IFN-b, IFN-g, IL-1a, IL-1b, IL-1ra, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IL-8/CXCL8, IL-10, IL-12 p70, IL-13, IL-15, IL-17A, IL-17E, IL-33, PD-L1, PDGF-AA, PDGF-AB/BB, TGF-a, TNF-a, TNFSF10, VEGF.
Time Frame
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.
Title
Change in Gene Expression Alteration by THC between HIV-positive and HIV-negative Groups
Description
Quantity of each gene is measured via sequence transcriptome, and significant differences of quantified gene pre- and post-THC infusion are identified as THC-induced gene expression alteration. Results will be compared between HIV-positive and HIV-negative subjects.
Time Frame
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.
Title
Change in Cytokine Profile by THC between HIV-positive and HIV-negative Groups
Description
Cytokine profile will be measured using Luminex Performance Human Cytokine Discovery panel before and after study drug infusion. Results will be compared between HIV-positive and HIV-negative subjects. The 45 cytokines selected based on their established role in immune functioning are: CCL2/MCP-1, CCL3/MIP-1a, CCL4/MIP-1b, CCL5/RANTES, CCL11/Eotaxin, CCL19/MIP-3b, CCL20/MIP-3a, TNFSF5, CX3CL1/Fractalkine, CXCL1/GROa, CXCL2/GROb, CXCL10/IP-10, EGF, FGF2, FLT3L, G-CSF, GM-CSF, Granzyme B, IFN-a2, IFN-b, IFN-g, IL-1a, IL-1b, IL-1ra, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IL-8/CXCL8, IL-10, IL-12 p70, IL-13, IL-15, IL-17A, IL-17E, IL-33, PD-L1, PDGF-AA, PDGF-AB/BB, TGF-a, TNF-a, TNFSF10, VEGF.
Time Frame
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 Outcome Measure Information:
Title
Perceptual Alterations
Description
Perceptual alterations will be measured using scales such as the Clinician Administered Dissociative Symptoms Scale (CADSS), a scale consisting of 19 self-report items and 8 clinician-rated items (0 = not at all, 4 = extremely) that we have shown to be sensitive to THC effects. The scale captures alterations in environmental/time/body perception, feelings of unreality, and memory impairment.
Time Frame
Perceptual alterations will be measured before study drug infusion and 70, 140, and 300 minutes after study drug infusion.
Title
Cannabis Subjective Effects
Description
Various feeling states associated with cannabis intoxication will be measured using a self-reported visual analog scale of feeling states ("high", "calm and relaxed", and "tired") associated with cannabis effects. Subjects will be asked to score the perceived intensity of these feeling states at that moment on a 100 mm line (0 = not at all, 100 = extremely). These data will be captured to validate that the experiment is relevant to cannabis effects.
Time Frame
Cannabis subjective effects will be measured before study drug infusion and 70, 140, and 300 minutes after study drug infusion.
Title
Cannabinoid Relevant Molecules
Description
Blood will be sampled for cannabinoid relevant molecules before and after study drug infusion. Cannabinoid relevant molecules will include THC and THC-COOH levels.
Time Frame
Blood will be collected before study drug infusion and at 70, 140, and 300 minutes after study drug infusion.
Title
Change in total immediate recall on the RAVLT.
Description
Memory, attention, and executive function will be measured before and after study drug administration using the Rey Auditory Verbal Learning Task (RAVLT).
Time Frame
The RAVLT will be administered prior to study drug administration at approximately 25 minutes after study drug administration.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
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)
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Brooklyn Bradley, BS
Phone
203-932-5711
Ext
4495
Email
bb889@yale.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Chloe Ouchida, BA
Phone
203-932-5711
Ext
2557
Email
chloe.ouchida@yale.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Deepak C D'Souza, MD
Organizational Affiliation
Yale University Professor of Psychiatry
Official's Role
Principal Investigator
Facility Information:
Facility Name
VA Connecticut Healthcare System
City
West Haven
State/Province
Connecticut
ZIP/Postal Code
06516
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Deepak C D'Souza, MD
Phone
203-932-5711
Ext
2594
Email
deepak.dsouza@yale.edu
First Name & Middle Initial & Last Name & Degree
Christina Luddy, BS
Phone
203-932-5711
Ext
4549
Email
christina.luddy@yale.edu

12. IPD Sharing Statement

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In Vivo Study of THC-induced Immune-genome Changes at Single Cell Solution in HIV-infected Humans

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