Cannabis Effects on Antiretroviral Therapy Pharmacokinetics and Neurotoxicity
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- 1a i. Antiretroviral therapy (ART) drug concentration in blood
研究概览
简要总结
This study will address whether cannabis affects antiretroviral therapy (ART) drug concentrations, mood, and thinking. The project will have two phases. Phase 1 is an observational study, in which 120 people will be assessed to evaluate the effects of chronic cannabis use on ART drug concentrations, mood, and thinking. In Phase 2, the study will administer cannabis (or placebo) to 40 people to examine its acute effects on ART drug concentrations.
详细描述
People with human immunodeficiency virus (HIV) commonly use cannabis but whether cannabis affects the antiretroviral therapy (ART) that treats HIV is not well known. Cannabis can inhibit the activity of enzymes that metabolize and eliminate ART drugs from the body, which could result in higher concentrations of ART drugs in the body. Cannabis may also affect the distribution of ART drugs into the brain, which could have both beneficial (e.g., better HIV control) and detrimental (e.g., toxicity) effects. The effects of cannabis may are likely influenced by factors like how much is used (e.g., light vs. heavy use) and the route of use (e.g., smoked vs. ingested). This study will address whether cannabis affects ART concentrations in blood and cerebrospinal fluid as well as mood, and thinking. The project will have two phases. Phase 1 is an observational study, in which 120 people will be assessed once to evaluate the effects of chronic cannabis use on ART drug concentrations, mood, and thinking. In Phase 2, the study will administer cannabis (or placebo) to 40 people to examine its acute effects on ART drug concentrations.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Participants will randomly receive one of the study products at each visit. All participants will receive all three of the study products. Allocation assignment of visits will be assigned using a randomization string provided by the statistician. The allocation schedule will be kept in the pharmacy and concealed from all other study personnel.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
THC Cannabis
11.86% THC/ 1.12% CBD
干预措施: THC Cannabis (Drug)
CBD Cannabis
0.35% THC/ 11.27% CBD
干预措施: CBD Cannabis (Drug)
Placebo
≤ 0.03% THC/ ≤ 0.05% CBD
干预措施: Placebo (Drug)
结局指标
主要结局
1a i. Antiretroviral therapy (ART) drug concentration in blood
时间窗: Cross-sectional; measured before ART ingestion
This will be done separately for participants who use ART drugs that are predominantly metabolized by cytochrome P450 (CYP) or uridine 5'-diphospho-glucuronosyltransferase (UGT) (estimated N=60 in each).
1a ii. Cerebrospinal fluid (CSF)/plasma ratio of ART drug concentrations
时间窗: Cross-sectional; measured before ART ingestion
This will be done separately for CYP and UGT groups (estimated N=60 in each).
1a iii. Change in ART drug concentrations in blood
时间窗: 2 hours; measured before ART ingestion and at 2 hours after the ART ingestion
This will be done separately for CYP and UGT groups (estimated N=60 in each).
1a iv. Change in CSF/plasma ratio of ART drug concentrations
时间窗: 2 hours; measured before ART ingestion and at 2 hours after the ART ingestion
This will be done separately for CYP and UGT groups (estimated N=60 in each).
1b i. Effects of placebo, THC, and CBD on ART drug concentration
时间窗: 5 hours
The investigators will use a mixed effects model to assess effects of acute cannabis treatment (placebo, THC, or CBD: N=40) on the area under the time-drug concentration curve.
1b ii. Effects of placebo, THC and CBD on the CSF/plasma ratio of ART drug concentrations
时间窗: 5 hours
The investigators will use a mixed effects model to assess effects of acute cannabis treatment (placebo, THC, or CBD: N=40) on CSF/plasma ratio of ART drug concentrations
1b iii. Comparison between the effects of placebo and THC on ART pharmacokinetics and between the effects of placebo and CBD on ART pharmacokinetics
时间窗: 3 to 30 days
Comparison of the the area under the time-concentration curve of ART pharmacokinetics for placebo and THC and placebo and CBD (n=40). The effect size will be measured as the standardized difference in mean outcomes between any two groups (Cohen's d).
1b iv. Comparison between the effects of placebo and CBD on the CSF/plasma ratio of ART drug concentrations and between the effects of placebo and THC on the CSF/plasma ratio of ART drug concentrations
时间窗: 3 to 30 days
Comparison of the the CSF/plasma ratio of ART drug concentrations with placebo and CBD and with placebo and THC (n=40). The effect size will be measured as the standardized difference in mean outcomes between any two groups (Cohen's d).
2a. Effects of chronic cannabis use on the CSF/serum albumin ratio and P-glycoprotein (P-gp) expression.
时间窗: 3 to 30 days
Multivariate linear regression will be used to regress markers of blood-brain barrier integrity and P-gp on cannabis use (n = 120), then ART drug concentrations on blood-brain barrier integrity and P-gp separately for the UGT and CYP groups
2b. Examine the correlation between ART concentration in CSF and blood during placebo treatment compared to THC and CBD administration.
时间窗: 3 to 30 days
The investigators will use a mixed effects model to evaluate the effects of cannabis on the correlation between ART concentration in CSF and blood (n = 40).
2c. Effects of THC or CBD on uridine 5'-diphospho-glucuronosyltransferase (UGT) activity compared to placebo.
时间窗: 3 to 30 days
The investigators will use a mixed effects model to examine the effects of drug treatment on UGT metabolism (n = 40).
3a. i. Correlation between CD4+ T-cell count and ART drug concentration.
时间窗: Up to 5 weeks: baseline to administration visits
Multivariable linear regressions will be used for testing correlation between CD4+ T-cell count and ART drug concentration (N=60 in each UGT and CYP groups).
3a. ii. Correlation between HIV DNA and ART drug concentration.
时间窗: Up to 5 weeks: baseline to administration visits
Multivariable logistic regressions will be used for testing correlation between HIV DNA and ART drug concentration (N=60 in each UGT and CYP groups).
3b i. Effects of cannabis use on the correlation between ART and neurocognitive performance.
时间窗: 3 to 30 days
The total cognitive outcome from the National Institutes of Health Toolbox will be regressed in multivariable models on ART drug concentration and cannabis use, their interaction, and known confounders and relevant covariates. Values range from 0 to 100 with lower values being worse.
3b ii. Effects of cannabis use on the correlation between ART and depression.
时间窗: 3 to 30 days
Depression (measured with the Beck Depression Inventory-II) will be regressed in multivariable models on ART drug concentration and cannabis use, their interaction, and known confounders and relevant covariates.
3b iii. Effects of cannabis use on the correlation between ART and emotional health.
时间窗: 3 to 30 days
The National Institutes of Health Toolbox-Emotional Battery outcome, Negative Affect, will be regressed in multivariable models on ART drug concentration and cannabis use, their interaction, and known confounders and relevant covariates. This measure ranges between 0 and 100 with higher values reflecting more Negative Affect.
3b iv. Effects of cannabis use on the correlation between ART and emotional health.
时间窗: 3 to 30 days
The National Institutes of Health Toolbox-Emotional Battery outcome, Social Satisfaction, will be regressed in multivariable models on ART drug concentration and cannabis use, their interaction, and known confounders and relevant covariates. This measure ranges between 0 and 100 with lower values reflecting worse Social Satisfaction.
3b v. Effects of cannabis use on the correlation between ART and emotional health.
时间窗: 3 to 30 days
The National Institutes of Health Toolbox-Emotional Battery outcome, Psychological Wellbeing, will be regressed in multivariable models on ART drug concentration and cannabis use, their interaction, and known confounders and relevant covariates. This measure ranges between 0 and 100 with lower values reflecting worse Psychological Wellbeing.
3b vi. Effects of cannabis use on the correlation between ART and neurotoxicity.
时间窗: 3 to 30 days
A measure of neurotoxicity (mitochondrial DNA) will be regressed in multivariable models on ART drug concentration and cannabis use, their interaction, and known confounders and relevant covariates.
3b vii. Effects of cannabis use on the correlation between ART and neurotoxicity.
时间窗: 3 to 30 days
A measure of neurotoxicity (8-hydroxydeoxyguanosine) will be regressed in multivariable models on ART drug concentration and cannabis use, their interaction, and known confounders and relevant covariates.
3b viii. Effects of cannabis use on the correlation between ART and neurotoxicity.
时间窗: 3 to 30 days
A measure of neurotoxicity (F2-isoprostane) will be regressed in multivariable models on ART drug concentration and cannabis use, their interaction, and known confounders and relevant covariates.
次要结局
- 1b v. Comparison between the effects of THC and CBD on ART pharmacokinetics.(3 to 30 days)
- 1b vi. Comparison between the effects of THC and CBD on the CSF/plasma ratio of ART drug concentrations.(3 to 30 days)
研究者
Scott Letendre
Professor
University of California, San Diego