Non-Invasive Vagal Nerve Stimulation in Patients with Opioid Use Disorders

阿片类药物使用障碍患者的无创迷走神经刺激

• 批准号: 10718694
• 负责人: James Douglas Bremner
• 金额: $ 195.21万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-15 至 2026-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10718694
• 关键词: Non; Invasive; Vagal; Nerve; Stimulation

Treatment of Opioid Use Disorders (OUDs) includes medications with effects on opioid receptors such as buprenorphine, but access is limited for many patients and others are opposed to treating addictions with medications that have opioid agonist properties. Naltrexone is an opioid antagonist that is more acceptable for many patients, and recent studies show it to be equivalent in efficacy. Initiation of treatment with long-acting naltrexone, however, requires a period of abstinence of about seven days during which time patients suffer from intense symptoms of withdrawal with a risk of relapse that can lead to overdose-related death. Opioids have an inhibitory effect on norepinephrine and the sympathetic nervous system, and many symptoms of withdrawal are driven by rebound activation of these systems. Dopaminergic systems in brain areas including ventral striatum (nucleus accumbens) and medial prefrontal cortex (anterior cingulate) play an important role in opioid addiction, craving and relapse, as do increases in inflammation. This project will assess a form of neuromodulation involving non-invasive electrical stimulation of the vagus nerve that may play a useful role during the period of opioid withdrawal before the initiation of long-term naltrexone treatment in blocking norepinephrine, sympathetic, and inflammatory responses and enhancing peripheral parasympathetic and central brain function in areas modulating drug craving (ventral striatum, anterior cingulate). Our preliminary data on the effects of non-invasive Vagal Nerve Stimulation (nVNS) on stress response in traumatized human subjects and patients with posttraumatic stress disorder (PTSD) show that nVNS reliably blocks peripheral sympathetic and enhances parasympathetic function, reduces inflammatory responses (interleukin-6, or IL-6), and enhances central brain responses (anterior cingulate) to stress. We now propose to apply this technology to the treatment of patients with OUDs. Following verification using modelling and determination of optimal dosing parameters, we will use these parameters to assess effects of nVNS versus sham stimulation on opioid craving, peripheral autonomic, cardiovascular, inflammatory, and brain functional responses measured with High-Resolution Positron Emission Tomography (HR-PET) and radiolabeled water to videos of drug cues in recently treated patients with OUDs. Based on the outcome of this research, we will proceed to the UH3 phase, which will involve a randomized, sham-controlled trial of nVNS in patients with OUDs during the one to two week period of opioid withdrawal followed by assessment of craving, HR-PET imaging of both brain function and brain dopaminergic function, and assessment of peripheral autonomic, cardiovascular and inflammatory responses in conjunction with administration of nVNS or sham. We hypothesize that nVNS will reduce opioid craving and inflammatory, peripheral autonomic and cardiovascular responses and enhance brain responses (anterior cingulate function and dopamine function in ventral striatum), and promote successful conversion to long-acting naltrexone, in patients with OUDs.

阿片类药物使用障碍（OUDS）的治疗包括对阿片类药物受体作用的药物，例如 丁丙诺啡，但对于许多患者而言，访问受到限制，其他患者则反对治疗成瘾 具有阿片类激动剂特性的药物。纳曲酮是阿片类药物拮抗剂，更可接受 许多患者，最近的研究表明，它在疗效方面是等效的。长效开始治疗 然而，纳曲酮需要一段时间的禁欲约七天，在此期间患者遭受痛苦 从戒断的强烈症状和复发的风险中，可能导致与药物过量相关的死亡。阿片类药物 对去甲肾上腺素和交感神经系统有抑制作用，许多症状 撤回是由这些系统的反弹激活驱动的。大脑区域的多巴胺能系统，包括 腹侧纹状体（伏隔核）和内侧前额叶皮层（前扣带回）在 阿片类药物成瘾，渴望和复发，炎症的增加也是如此。该项目将评估一种形式 神经调节涉及迷走神经的非侵入性电刺激，可能起作用 在启动长期纳曲酮治疗之前，阿片类药物戒断期间 去甲肾上腺素，交感神经和炎症反应，并增强外周副交感神经和 调节药物渴望的区域中央脑功能（腹侧纹状体，前扣带回）。我们的初步 关于非侵入性迷走神经刺激（NVN）对受创伤性人体压力反应的影响的数据 受试者和创伤后应激障碍（PTSD）的患者表明，NVN可靠地阻塞外围 交感神经并增强副交感神经功能，减少炎症反应（白介素6或IL-6）， 并增强中央大脑反应（前扣带回）压力。我们现在建议应用这项技术 对OUDS患者的治疗。使用建模和确定最佳验证后进行验证 给药参数，我们将使用这些参数来评估NVN与假刺激对阿片类药物的影响 渴望，外周自主神经，心血管，炎症和脑功能反应 高分辨率正电子发射断层扫描（HR-PET）和放射性标记的水，用于药物提示视频 最近治疗了OUDS患者。根据这项研究的结果，我们将继续进行UH3 阶段，该阶段将涉及NVN的随机，假对照试验，以期在OUDS患者中 两周的阿片类药物戒断期，然后评估渴望，两个大脑的HR-PET成像 功能和脑多巴胺能功能，以及外周自主神经，心血管和 炎症反应与NVN或假施用结合。我们假设NVN会 减少阿片类药物的渴望和炎症，周围自主神经和心血管反应并增强 脑反应（前扣带回功能和腹侧纹状体的多巴胺功能），并促进 OUDS患者成功地转化为长效纳曲酮。