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: 10613308
• 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/10613308
• 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; 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; Productivity; Psychotherapy; Quality of life; Questionnaires; Randomized; Recovery; Rehabilitation therapy; Relapse; Research; Research Personnel; Risk; Sampling; Self Administration; Self Care; Services; Stimulus; Stress; Structure; Symptoms; Technology; Time; Training; 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; 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; heat stimulus; improved; innovation; military veteran; negative affect; neural; neural correlate; neuroadaptation; neuroregulation; novel; physical state; psychologic; psychological distress; psychosocial; randomized, clinical trials; recruit; reduce symptoms; response; side effect; social stigma; substance use; transmission process; 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% 的美军 退伍军人，给该人群和 VA 医疗系统带来了沉重的负担。 完成治疗的退伍军人中有一半以上在 6 个月内复发，这凸显了这一必要性 改善治疗或不同的治疗目标 慢性、大量饮酒会导致失衡。 体内平衡导致禁欲期间的心理和身体困扰以及饮酒的冲动 缓解这些症状以恢复体内平衡的无创迷走神经刺激 (nVNS) 是一种低风险形式。 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 我们在动物模型中发现，nVNS 可通过以下方式减弱 AUD 中与痛苦相关的渴望： 改变自主神经系统并改变对生理内在身体感觉的感知 我们还认为，nVNS 可以改善功能结果和生活质量。 退伍军人用澳元。 拟议的研究将通过添加一个小子样本来利用 VA 资助的正在进行的研究的基础设施 被诊断为 AUD 的退伍军人（至少有一项因饮酒导致的功能障碍，目前 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，旨在评估 然后受试者将在家中自行进行 nVNS/假手术。 每天两次，持续 7 天，然后返回进行随访，在此期间将重复所有研究组成部分。 功能障碍、生活质量、心理和生理困扰的行为评估，以及 渴望将在基线、刺激后和随访时进行。 拟议研究的目的是确定应用 nVNS 作为康复方法的可行性和可接受性 此外，该研究还将评估 nVNS 在改善 AUD 方面的初步效果。 功能结果和生活质量，减少痛苦和渴望，以及改变神经激活模式 在涉及痛苦和疼痛的感知和意识的大脑区域中，拟议的工作具有以下特点： 有潜力带来创新、低风险的治疗方案，有望显着改善护理和治疗 退伍军人的生命，因为需要 AUD 的替代治疗，因此，这种新型 AUD 治疗可以。 对于不能耐受药物治疗以及有机会或有认知能力的退伍军人特别有益 成为心理治疗障碍的耻辱限制或担忧 该 CDA-1 的直接职业目标。 奖项的目的是为申请人提供临床研究经验和所需的中试数据 竞争性 CDA-2 拨款申请旨在测试 nVNS 作为 AUD 相关治疗选择的功效 在更大的样本中研究症状和功能康复，并解决长期的作用机制。 目标是引导申请人发展成为 VA 内富有成效的临床研究人员 医疗保健系统拥有基于神经科学的 AUD 康复专业知识。