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

基本信息

批准号：
10682459
负责人：
Eric Porges
金额：
$ 40.13万
依托单位：
UNIVERSITY OF FLORIDA
依托单位国家：
美国
项目类别：
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/10682459
关键词：
Activities of Daily Living Alcohol consumption Alcohols Anti-Inflammatory Agents Bacteria Biological Biological Markers Blood Brain Cardiovascular system Cognition Cognitive Collaborations 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 Inflammation Inflammatory Intervention 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 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 cholinergic clinically significant co-infection cognitive function cognitive testing comorbidity cytokine design dysbiosis effective intervention fecal microbiome gamma-Aminobutyric Acid gastrointestinal gut dysbiosis gut microbiome gut-brain axis high risk high risk sexual behavior immune function immune reconstitution improved indexing microbial microbiome composition microbiota-gut-brain axis mortality neural network neuroimaging neuroinflammation poor health outcome pre-doctoral probiotic supplementation randomized, clinical trials scale up systemic inflammatory response transmission process treatment adherence vagus nerve stimulation viral transmission

项目摘要

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).

RC2 总结研究部分 2 (RC2) 的总体目标是确定两种非侵入性生物技术是否干预措施，经皮迷走神经刺激（tVNS）和益生菌补充干预（PBI），将改善人们的认知和大脑功能、全身和神经炎症以及肠道微生物组健康患有艾滋病毒（PWLH）的人是饮酒的高危人群。这项研究还将描述肠-脑轴的机制，该机制鉴于 PLWH 中饮酒对认知和大脑产生不良影响的因素，这一点尤为重要如果 tVNS 和/或 PBI 的有益作用能够得到解决，那么它也具有相当大的公共卫生意义。事实证明，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抗逆转录病毒疗法 (ART) 时代死亡率显着降低，但这种情况很常见（约 50% 的患病率）。在免疫功能重建且病毒载量无法检测到的感染者中，合并症仍然很常见感染者中普遍存在的高风险饮酒不仅会导致功能不良。认知和大脑功能障碍，而且还会进一步恶化合并症（例如肝病、肝炎合并感染、肥胖、心血管和胃肠功能障碍），并降低治疗依从性，同时增加高风险性行为的倾向、更糟糕的健康结果以及病毒的传播。鉴于需要采取有效干预措施来改善 PLWH 的认知和健康结果，这一点非常重要。为了检验这些假设，我们将进行一项混合随机临床试验，该试验将招募 80 名高危感染者来自南方艾滋病酒精研究联盟支持的现有研究基础设施的风险饮酒者 (SHARC) 在 2x2 因子设计中，参与者将被随机分配到 4 种条件之一（tVNS+安慰剂、假手术）。刺激+安慰剂、tVNS+益生菌、假刺激+益生菌）我们将获得有关酒精消耗的数据，三个时间点（基线、30 天、 90 天）。