In Vivo Study of THC-induced Immune-genome Changes at Single Cell Solution in HIV-infected Humans
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- Change in Gene Expression Alteration
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Active Delta-9-THC
Active Delta-9-THC (0.03 mg/kg) administered intravenously.
干预措施: Active Delta-9-THC (Drug)
结局指标
主要结局
Change in Gene Expression Alteration
时间窗: 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.
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 by THC between HIV-positive and HIV-negative Groups
时间窗: 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.
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.
Change in Cytokine Profile
时间窗: 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.
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
时间窗: 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.
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.
次要结局
- Perceptual Alterations(Perceptual alterations will be measured before study drug infusion and 70, 140, and 300 minutes after study drug infusion.)
- Change in total immediate recall on the RAVLT.(The RAVLT will be administered prior to study drug administration at approximately 25 minutes after study drug administration.)
- Cannabis Subjective Effects(Cannabis subjective effects will be measured before study drug infusion and 70, 140, and 300 minutes after study drug infusion.)
- Cannabinoid Relevant Molecules(Blood will be collected before study drug infusion and at 70, 140, and 300 minutes after study drug infusion.)
研究者
Deepak C. D'Souza
Professor of Psychiatry
Yale University