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: 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
• 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

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