Non-invasive Vagal Nerve Stimulation to improve functional outcomes in Veterans with Alcohol Use Disorder

无创迷走神经刺激可改善患有酒精使用障碍的退伍军人的功能结果

• 批准号: 10410173
• 负责人: Ruth Klaming
• 金额: --
• 依托单位: VA SAN DIEGO HEALTHCARE SYSTEM
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-05-01 至 2024-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10410173
• 关键词: Abstinence; Address; Affect; Affective; Alcohol consumption; Alcohols; Analgesics; Animal Model; Animals; Anxiety; Applications Grants; Attenuated; Autonomic nervous system; Award; Awareness; Behavior assessment; Brain region; Caring; Chronic; Clinical; Clinical Research; Cognitive; Data; Data Collection; Development; Diagnosis; Distress; Dropout; Effectiveness; Emotional; Employment; Equipment and supply inventories; Feasibility Studies; Functional Magnetic Resonance Imaging; Functional disorder; Funding; Goals; Health; Healthcare Systems; Heavy Drinking; Home; Homeostasis; Human; Impairment; Infrastructure; Insula of Reil; Intervention; Interview; Lead; Measures; Mental Depression; Mental disorders; Nerve; Neurosciences; Outcome; Pain; Pain interference; Pathway interactions; Patients; Pattern; Perception; Pharmaceutical Preparations; Pharmacotherapy; Physiological; Population; Post-Traumatic Stress Disorders; Psychotherapy; Quality of life; Questionnaires; Randomized; Randomized Clinical Trials; Recovery; Rehabilitation therapy; Relapse; Research; Research Personnel; Research Training; Risk; Sampling; Self Administration; Self Care; Services; Stimulus; Stress; Structure; Symptoms; Technology; Time; Translating; Treatment Cost; Vagus nerve structure; Veterans; Visit; Work; acceptability and feasibility; addiction; alcohol abuse therapy; alcohol craving; alcohol exposure; alcohol rehabilitation; alcohol relapse; alcohol use disorder; alternative treatment; base; bodily sensation; career; chronic pain; community reintegration; cost; craving; design; diaries; drinking; drug relapse; efficacy evaluation; efficacy testing; emotional distress; experience; follow-up; functional disability; functional improvement; functional outcomes; heat stimulus; improved; innovation; military veteran; negative affect; neural correlate; neuroadaptation; neuroregulation; novel; physical state; psychologic; psychological distress; psychosocial; recruit; reduce symptoms; relating to nervous system; response; side effect; social stigma; substance use; treatment adherence; treatment risk

Alcohol use disorder (AUD) is a serious mental health disorder that affects more than 40% of US military Veterans, presenting a major burden to this population and to the VA Healthcare System. Relapse rates of AUD are extremely high; over half of Veterans who complete treatment relapse within 6 months, highlighting the need for improved treatments or differing treatment targets. Chronic, heavy drinking leads to an imbalance in homeostasis resulting in psychological and physical distress during periods of abstinence, and the urge to drink to relieve these symptoms to restore homeostasis. Noninvasive vagal nerve stimulation (nVNS) is a low-risk form of neuromodulation that has been shown to alleviate anxiety and chronic pain, and to reduce drug and alcohol relapse in animal models. We hypothesize that nVNS attenuates distress-related craving in AUD in humans by modifying the autonomic nervous system and changing the perception of inner bodily sensations of physiological and affective distress. We also hypothesize that nVNS improves functional outcomes and quality of life in Veterans with AUD. The proposed research will utilize the infrastructure of an ongoing VA-funded study by adding a small subsample of Veterans who meet for a diagnosis of AUD (with at least one functional disability due to alcohol use, current alcohol craving, and current heavy drinking). Subjects will be randomly assigned to receive nVNS or sham stimulation prior to performing a well-validated functional Magnetic Resonance Imaging task designed to assess neural correlates of physical distress (via a heat stimulus). Subjects will then self-administer nVNS/sham at home twice a day for 7 days and return for a follow-up visit, during which all study components will be repeated. Behavioral assessments of functional disability, quality of life, psychological and physiological distress, and craving will be administered at baseline, after stimulation, and at follow-up. The aim of the proposed study is to establish feasibility and acceptability of applying nVNS as a rehabilitative treatment for AUD. In addition, the study will evaluate the preliminary effectiveness of nVNS in improving functional outcomes and quality of life, in reducing distress and craving, and in altering neural activation patterns in brain regions involved in the perception and awareness of distress and pain. The proposed work has the potential to lead to innovative, low-risk treatment options with high promise to significantly improve the care and lives of Veterans as there is a need for alternative treatments for AUD. As such, this novel AUD treatment could be particularly beneficial for Veterans who do not tolerate pharmacotherapy, and who have access or cognitive limitations or stigma concerns that act as barriers to psychotherapy. The immediate career goal for this CDA-1 award is to provide the applicant with the clinical research experience and the pilot data necessary for a competitive CDA-2 grant application aimed at testing the efficacy of nVNS as a treatment option for AUD-related symptoms and functional rehabilitation in a larger sample, and to address mechanisms of action. The long-term goal is to guide the applicant’s development toward becoming a productive clinical researcher within the VA Healthcare System with expertise in neuroscience-based rehabilitation of AUD.

酒精使用障碍（AUD）是一种严重的精神健康障碍，影响超过40%的美国军人 退伍军人，提出了一个重大的负担，这一人口和VA医疗保健系统。AUD复发率 非常高;超过一半的退伍军人谁完成治疗复发6个月内，强调需要 用于改进治疗或不同的治疗目标。长期大量饮酒会导致 体内平衡导致禁欲期间的心理和身体痛苦，以及饮酒的冲动 缓解这些症状以恢复体内平衡无创迷走神经刺激（nVNS）是一种低风险的形式 神经调节已被证明可以减轻焦虑和慢性疼痛，并减少药物和酒精 在动物模型中复发。我们假设nVNS通过以下方式减弱人类AUD中的痛苦相关渴望： 修改自主神经系统和改变生理的内在身体感觉的感知， 和情感困扰我们还假设，nVNS改善功能结果和生活质量， 有AUD的人。 拟议的研究将利用正在进行的VA资助的研究的基础设施，增加一个小的子样本 符合AUD诊断的退伍军人（至少有一种因饮酒造成的功能障碍，目前 酒精渴望，以及目前的大量饮酒）。受试者将被随机分配接受nVNS或假手术 在执行经过充分验证的功能性磁共振成像任务之前进行刺激，该任务旨在评估 神经相关的身体痛苦（通过热刺激）。然后，受试者将在家中自行给予nVNS/假手术 每天两次，持续7天，并返回进行随访访视，在此期间将重复所有研究组成部分。 对功能残疾、生活质量、心理和生理困扰的行为评估，以及 在基线、刺激后和随访时给予渴望。 本研究的目的是确定应用nVNS作为康复治疗的可行性和可接受性 治疗AUD。此外，该研究将评估nVNS在改善 功能结果和生活质量，减少痛苦和渴望，并改变神经激活模式 大脑中负责感知和感知痛苦的区域。拟议的工作有 有可能导致创新的，低风险的治疗选择，并有很大的希望，以显着改善护理， 因为有必要为AUD提供替代治疗。因此，这种新的AUD治疗方法可以 对于不耐受药物治疗且有机会或认知能力的退伍军人特别有益 限制或耻辱的担忧，作为心理治疗的障碍。CDA-1的近期职业目标 奖励是为申请人提供临床研究经验和必要的试点数据， 竞争性CDA-2赠款申请，旨在测试nVNS作为AUD相关治疗选择的疗效 症状和功能康复在更大的样本，并解决行动机制。长期 目标是指导申请人的发展，成为一个富有成效的临床研究人员在VA 医疗保健系统具有基于神经科学的AUD康复专业知识。