Vagus Nerve Stimulation in Fibromyalgia

迷走神经刺激治疗纤维肌痛

• 批准号: 6925907
• 负责人: GUDRUN LANGE
• 金额: $ 50.79万
• 依托单位: UNIV OF MED/DENT OF NJ-NJ MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-16 至 2008-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6925907
• 关键词: clinical research; electrostimulus; fibromyalgia; human subject; human therapy evaluation; hyperalgesia; nervous system prosthesis; pain threshold; patient oriented research; quality of life; vagus nerve

DESCRIPTION (provided by applicant): Fibromyalgia Syndrome (FMS) is a chronic pain disorder of unknown origin, characterized by diffuse body pain and tenderness. Evidence is accumulating that the pathogenesis of FMS may be associated with central dysregulation of pain regulatory systems manifesting itself psychophysically in abnormally high pain sensitivity and intolerance thresholds. Based on physiological data derived from animals and psychophysical data derived from humans, VNS therapy was found to reduce the intensity of laboratory pain, especially when sensitization of the central pain regulatory system, known as wind-up, was induced. Wind-up is thought to underlie chronic pain in FMS. Thus, VNS therapy may be a viable adjunctive treatment option for FMS patients. Conventional drug and behavioral therapies have proven to be largely unsuccessful in relieving FMS pain over time. While opioid maintenance therapy, the current 'last resort' treatment option for FMS patients with severe, unrelenting pain, is efficacious, it is often avoided for fear of addiction. Thus, unrelieved FMS pain leads to poor quality of life, disability, economic disadvantage, and over utilization of the health care system. VNS has the potential to be a break-through non-pharmacological treatment modality to relieve FMS pain and halt this process. FMS patients who are disabled and depressed are usually considered to have the poorest prognosis. The proposed pilot study will be an open label, non-randomized single-arm, longitudinal, single-center study of VNS. We plan to implant and study 30 FMS patients representative of the spectrum of refractory FMS patients. All patients will have been treatment resistant to at least two levels of a conventional four level pharmacological FMS pain management protocol. In line with recent prevalence estimates, one-third of our selected FMS sample will be work disabled and two-thirds will not be. Likewise, one-third of FMS patients studied will not have a concurrent depressive disorder, while two-thirds will. The primary aim of this pilot study is to define the limits of VNS safety and tolerability in patients with refractory FMS. This study will provide data regarding the proportion of FMS patients tolerating implantation of the VNS device, activation, and ramp up of VNS output current, as well as stimulation over a 3-months, acute, and a 9 months follow-up study period. In addition, we will estimate the range of VNS output current tolerated and determine whether the rates of any adverse events are higher in FMS than epilepsy or depression samples. These data will inform the design of a Phase HI trial about maximal stimulation intensities and the minimum duration of a trial that is possible in these patients. The secondary aim of this study, assuming VNS is tolerated, is to assess the impact of VNS therapy on symptoms of FMS (including pain intensity, physical function, patient's global impression of change [FM20], mood, and quality of life, as well as laboratory measures of pain sensitivity).

描述（由申请人提供）：纤维肌痛综合症（FMS）是一种来源不明的慢性疼痛疾病，其特征是弥漫性身体疼痛和压痛。越来越多的证据表明，FMS 的发病机制可能与疼痛调节系统的中枢失调有关，在心理物理上表现为异常高的疼痛敏感性和不耐受阈值。根据来自动物的生理数据和来自人类的心理物理数据，人们发现 VNS 疗法可以减轻实验室疼痛的强度，特别是在诱导中枢疼痛调节系统（称为“结束”）敏化时。结束被认为是 FMS 慢性疼痛的根源。因此，VNS 治疗可能是 FMS 患者可行的辅助治疗选择。随着时间的推移，传统的药物和行为疗法已被证明在缓解 FMS 疼痛方面基本上不成功。阿片类药物维持治疗是目前对于患有严重、持续性疼痛的 FMS 患者的“最后手段”治疗选择，虽然有效，但由于担心成瘾，通常会避免使用。因此，未缓解的 FMS 疼痛会导致生活质量差、残疾、经济劣势以及医疗保健系统的过度利用。 VNS 有潜力成为一种突破性的非药物治疗方式，以缓解 FMS 疼痛并阻止这一过程。残疾和抑郁的 FMS 患者通常被认为预后最差。 拟议的试点研究将是一项开放标签、非随机、单臂、纵向、单中心的 VNS 研究。我们计划植入并研究 30 名代表难治性 FMS 患者的 FMS 患者。所有患者都对传统四级药理学 FMS 疼痛管理方案中的至少两个级别具有治疗耐药性。根据最近的患病率估计，我们选择的 FMS 样本中有三分之一将丧失工作能力，三分之二则不会。同样，所研究的 FMS 患者中有三分之一不会并发抑郁症，而三分之二则会并发抑郁症。这项试点研究的主要目的是确定难治性 FMS 患者 VNS 安全性和耐受性的限度。这项研究将提供有关 FMS 患者耐受 VNS 装置植入、激活和 VNS 输出电流增加以及 3 个月急性研究和 9 个月随访研究期间刺激的比例的数据。此外，我们将估计 VNS 输出电流的耐受范围，并确定 FMS 中任何不良事件的发生率是否高于癫痫或抑郁症样本。这些数据将为 HI 期试验的设计提供有关这些患者可能的最大刺激强度和最短试验持续时间的信息。假设 VNS 可以耐受，本研究的次要目的是评估 VNS 治疗对 FMS 症状的影响（包括疼痛强度、身体功能、患者对变化的整体印象 [FM20]、情绪和生活质量，以及疼痛敏感性的实验室测量）。