Acute Neural and Immune Effects of Alcohol in People Living With HIV Infection
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 76
- 试验地点
- 2
- 主要终点
- Plasma Biomarker of Microbial Translocation
研究概览
简要总结
This study will examine whether moderate alcohol use in the context of HIV infection exacerbates inflammatory signaling in the immune system and brain. The study will recruit healthy individuals and people living with HIV infection who are otherwise in good health to participate. Participants will complete an experimental protocol that involves controlled alcohol administration and magnetic resonance imaging (MRI). Primary outcomes are plasma biomarkers of inflammation and MRI markers correlated with neuroinflammation. Results will advance understanding of the effects of alcohol use in people living with HIV infection.
详细描述
A sample of 56 participants, to include equal numbers of people living with HIV and uninfected controls, will be recruited to complete the experimental protocol. Participants will be randomized to one of the two beverage conditions (0.60 g/kg alcohol beverage, 0.00 g/kg placebo beverage). Blood samples will be collected at baseline (prior to beverage administration) and for three hours afterward. Cognitive performance and subjective intoxication will be assessed using standardized measures. MRI scans will be collected 4-5 hours after beverage consumption to capture neurobiological outcomes on the descending limb of blood alcohol.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- Double (Participant, Outcomes Assessor)
入排标准
- 年龄范围
- 21 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •21-60 years old;
- •Able to speak and read English at least at 8th grade level;
- •Alcohol use ≥.60 g/kg at least once in past year. In standard drinks, this amount translates to 1.9-3.0 drinks for an average-weight female and 2.4-3.9 drinks for an average-weight male.
- •Body mass index of 18.5-34.9 kg/m2;
- •Lab tests obtained in past year showing no evidence of acute/chronic Hepatitis B or C infection;
- •HIV-1 serostatus (positive or negative, depending on group) confirmed by standard clinical testing;
- •Able to consume soy and nuts safely (in order to consume the standardized meal).
排除标准
- •History of heavy drinking on a weekly or more frequent basis, with heavy drinking defined per NIAAA guidelines (≥4 drinks for women, ≥5 drinks for men on a given day), in the past two years;
- •More than five heavy drinking episodes in past 90 days;
- •Seeking or receiving treatment for alcohol/drug use, with exception of smoking cessation treatment;
- •Antibiotic use in past 1 month;
- •Daily use of non-steroidal anti-inflammatory drugs, which are known to increase gut permeability;
- •Disorder of the lower GI tract (e.g., inflammatory bowel disease, ulcerative colitis);
- •Positive urine test for amphetamine, cocaine, methamphetamine, opioids, or benzodiazepines (cannabis use will be assessed but is not an exclusion criterion);
- •Positive screening for past 12-month drug use disorder, indicated by Drug Abuse Screening Test-10 score >2;
- •Current major psychiatric disorder (current major depressive episode, bipolar disorder, psychotic disorder);
- •History of fainting, weakness, infection, excessive bruising, or extreme distress from blood draw;
- •Safety contraindication for MRI (e.g., metal implant); Note: copper intrauterine devices (IUDs) continue to be excluded due to Brown MRI research facility regulations but other non-metal IUDs are allowed;
- •Head trauma with loss of consciousness >10 min;
- •Inability to abstain from nicotine for 8 hours in-session;
- •For cannabis users: inability to abstain for 48 hours prior to study;
- •Pregnant, breastfeeding, or not using effective birth control;
- •Any other clinical condition or therapy that, in the physician's opinion, would make subject unsuitable for study or unable to comply with dosing requirement.
- •HIV-Specific Inclusion Criteria:
- •On antiretroviral therapy (ART) for ≥6 mos;
- •Labs in past 6 mos showing viral load <100 copies/mL, hemoglobin ≥10.0 g/dL, neutrophil count ≥1,000 cells/μL, and platelet count ≥150,000/μL;
- •No active AIDS diagnosis.
结局指标
主要结局
Plasma Biomarker of Microbial Translocation
时间窗: 0-3 hours
Lipopolysaccharide (LPS), measured in pg/ml
Plasma Biomarkers of Immune Activation
时间窗: 0-3 hours
soluble cluster of differentiation 163 (sCD163), measured in ng/ml
Cerebral Metabolites
时间窗: 5 hours
Magnetic resonance spectroscopy will be used quantify cerebral metabolites in brain regions of interest, specifically frontal lobe. Primary metabolites of interest include the summed peak of glutamate and glutamine; choline.
White Matter Diffusivity
时间窗: 5 hours
Diffusion-weighted MRI will be used to quantify diffusivity metrics in brain white matter. Primary outcome is fractional anisotropy (measured on a scale of 0-1, where 1 reflects total anisotropy).
次要结局
- Subjective Intoxication(0-5 hours)
- Cognitive Functioning(0-2 hours)