Cognitive and Inflammation Targeted Gut-Brain Interventions in People Living with HIV who are High-Risk Alcohol Users

对高危饮酒者艾滋病毒感染者进行认知和炎症针对性肠脑干预

• 批准号: 10304326
• 负责人: Eric Porges
• 金额: $ 40.3万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-10 至 2026-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10304326
• 关键词: Activities of Daily Living; Address; Alcohol consumption; Alcohols; Anti-Cholinergics; Anti-Inflammatory Agents; Bacteria; Biological; Biological Markers; Blood; Brain; Cardiovascular system; Cognition; Cognitive; Data; Data Science Core; Enrollment; Evaluation; Functional Magnetic Resonance Imaging; Functional disorder; Glutathione; Goals; HIV; HIV Infections; Health; Heavy Drinking; Hepatitis; Homeostasis; Human; Hybrids; Impaired cognition; Impairment; Inflammation; Inflammatory; Intervention; Intervention Studies; Intestinal permeability; Link; Liquid substance; Liver diseases; Machine Learning; Measures; Nerve; Neurocognition; Neurocognitive; Obesity; Outcome; Parasympathetic Nervous System; Participant; Pathogenicity; Pathologic; Pathway interactions; Peripheral; Persons; Phase; Placebos; Postdoctoral Fellow; Prevalence; Probiotics; Process; Property; Public Health; Quality of life; Randomized; Randomized Clinical Trials; Research; Research Infrastructure; Research Personnel; Rest; Risk Behaviors; Serum; System; Testing; Therapeutic; Therapeutic Effect; Training Programs; United States National Institutes of Health; Vagus nerve structure; Viral Load result; acceptability and feasibility; alcohol effect; alcohol research; alcohol risk; antiretroviral therapy; biological adaptation to stress; brain dysfunction; brain health; cell motility; clinically significant; co-infection; cognitive function; cognitive testing; comorbidity; cytokine; design; dysbiosis; effective intervention; fecal microbiome; functional improvement; gamma-Aminobutyric Acid; gastrointestinal; gut dysbiosis; gut microbiome; gut-brain axis; high risk; high risk sexual behavior; immune function; improved; indexing; microbial; microbiome composition; microbiota-gut-brain axis; mortality; neural network; neuroimaging; neuroinflammation; pre-doctoral; probiotic supplementation; reconstitution; relating to nervous system; scale up; systemic inflammatory response; transmission process; treatment adherence; vagus nerve stimulation; viral transmission

RC2 Summary The overarching goal of Research Component 2 (RC2) is to determine whether two non-invasive biological interventions, transcutaneous vagal nerve stimulation (tVNS) and a probiotic supplementation intervention (PBI), will improve cognitive and brain functioning, systemic and neuroinflammation, and gut microbiome health in people living with HIV (PWLH) who are high risk users of alcohol. The study will also delineate mechanisms of the gut-brain axis, which is particularly relevant, given that the factors underlying adverse cognitive and brain effects of alcohol use among PLWH remains unresolved. There is also considerable public health significance if beneficial effects of tVNS and/or PBI can be demonstrated, as cognitive disturbances that adversely impact health outcomes, functional abilities and quality of life are common (~ 50% prevalence), despite marked reductions in mortality in the era of antiretroviral therapies (ART). Among PLWH with reconstituted immune function and undetectable viral loads, comorbid conditions remain common and can have adverse functional consequences. High risk alcohol use, prevalent among PLWH, not only contributes to cognitive and brain dysfunction, but also further exacerbates comorbidities (e.g. liver disease, hepatitis coinfection, obesity, and cardiovascular and gastrointestinal dysfunction), and reduces treatment adherence while increasing the propensity for high risk sexual behaviors, worse health outcomes, and transmission of the virus. The study’s clinical significance is strong given the need for effective interventions to improve cognition and health outcomes in PLWH. To test these hypotheses, we will conduct a hybrid randomized clinical trial that will enroll 80 PLWH who are high risk drinkers from our existing research infrastructure supported by the Southern HIV Alcohol Research Consortium (SHARC). In a 2x2 factorial design, participants will be randomly assigned to one of 4 conditions (tVNS+placebo, sham- stimulaiton+placebo, tVNS+probiotic, sham-stimulation+probiotic). We will obtain data on alcohol consumption, cognitive assessments, blood biomarkers, stool microbiome, and neuroimaging at three timepoints (baseline, 30-days, 90 days).

RC 2总结 研究组成部分2（RC 2）的总体目标是确定两种非侵入性生物制剂是否 经皮迷走神经刺激（tVNS）和益生菌补充干预（PBI）将 改善认知和大脑功能，全身和神经炎症，以及生活在人类中的肠道微生物组健康 艾滋病毒携带者（PWLH）是酒精的高危使用者。这项研究还将描绘肠-脑轴的机制， 尤其重要的是，考虑到艾滋病毒携带者使用酒精对认知和大脑产生不良影响的潜在因素， 仍然没有解决。如果可以实现tVNS和/或PBI的有益效果，则也具有相当大的公共卫生意义。 已证明，认知障碍会对健康结果、功能能力和生活质量产生不利影响 尽管在抗逆转录病毒疗法（ART）时代死亡率显著降低，但仍很常见（约50%的患病率）。 在免疫功能重建和病毒载量检测不到的PLWH中，共病情况仍然很常见 并且可能具有不利的功能后果。高风险酒精使用，在艾滋病毒携带者中普遍存在，不仅有助于 认知和脑功能障碍，而且还进一步加重了合并症（例如肝病，肝炎合并感染， 肥胖、心血管和胃肠道功能障碍），并降低治疗依从性，同时增加 高风险性行为倾向、更差的健康结果和病毒传播。这项研究的临床 考虑到需要有效的干预措施来改善艾滋病毒携带者的认知和健康结果，这一点非常重要。 为了验证这些假设，我们将进行一项混合随机临床试验，将招募80名高血糖的PLWH， 风险饮酒者从我们现有的研究基础设施支持的南方艾滋病毒酒精研究联盟 （SHARC）。在2x2析因设计中，受试者将被随机分配至4种条件之一（tVNS+安慰剂，假手术- 刺激剂+安慰剂、tVNS+益生菌、假刺激+益生菌）。我们将获得酒精消费的数据， 在三个时间点（基线，30天， 90天）。