A staged, comprehensive investigation for developing insular deep brain stimulation to treat refractory chronic pain

开发岛叶深部脑刺激治疗难治性慢性疼痛的分阶段综合研究

• 批准号: 10437978
• 负责人: William Jeffrey Elias
• 金额: $ 105.6万
• 依托单位: UNIVERSITY OF VIRGINIA
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-20 至 2027-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10437978
• 关键词: Acute; Address; Adverse effects; Affective; Analgesics; Anterior; Attenuated; Bilateral; Biological Markers; Biotechnology; Brain; Brain Mapping; Cerebrum; Chronic; Clinical; Clinical Trials; Cognitive; Complex; Conscious; Cutaneous; Data; Deep Brain Stimulation; Development; Diffusion; Dose; Double-Blind Method; Electric Stimulation; Electrocardiogram; Electrodes; Electroencephalography; Electrophysiology (science); Enrollment; Epilepsy; Evidence based treatment; Financial Hardship; Home environment; Human; Implant; Inpatients; Insula of Reil; Interruption; Investigation; Lasers; Location; Magnetic Resonance Imaging; Maps; Measures; Methods; Monitor; Motivation; Movement Disorders; Nociception; Nonpharmacologic Therapy; Opiate Addiction; Opioid; Outcome Measure; Pain; Pain intensity; Patients; Pharmacology; Procedures; Process; Randomized; Refractory; Reporting; Research; Safety; Seizures; Sensory; Severities; Site; System; Translating; adverse event monitoring; base; chronic neuropathic pain; chronic pain; chronic pain management; chronic pain patient; chronic pain relief; clinical pain; design; experience; improved; insight; neuroimaging; neurophysiology; neuroregulation; novel; novel diagnostics; pain perception; pain reduction; pain relief; pain signal; painful neuropathy; primary outcome; prognostic; relating to nervous system; response; secondary outcome; side effect

PROJECT SUMMARY Patients with refractory chronic pain typically do not respond to traditional analgesics or weak opioids as these agents do not directly address the cause for their pain. Many chronic pain patients do not achieve satisfactory pain relief even with evidence-based treatment, or they do not tolerate effective doses because of adverse side effects. Deep brain stimulation (DBS) is already an established treatment for intractable movement disorders and epilepsy, and recent advancements in the fields of pain neurophysiology and biotechnology may facilitate the use of DBS as a nonpharmacological therapy for refractory chronic pain. In the first stage of the proposed project, we will enroll 12 subjects with refractory neuropathic pain to an inpatient clinical trial for insular brain mapping with acute stimulation and neurophysiological brain monitoring. Electrodes for stimulating and recording will be implanted stereotactically along the anterior-posterior axis of the insular cortex. Subjects with positive analgesic effects during acute insular stimulation in the first stage of the proposed project will continue to the second stage, which will consist of a randomized, sham-stimulation-controlled, double-blinded, cross-over clinical trial of chronic insular DBS with the purpose of obtaining safety and efficacy data for this procedure. Furthermore, we aim to develop neurophysiological biomarkers of pain by studying changes in neural activity. Safety data, effect size, and insular stimulation parameters obtained from this research will be used in the design of subsequent clinical trials. The neurophysiological pain biomarkers identified in this project will also aid the development of a novel, closed-loop insular DBS system, as well as new diagnostic/prognostic measures for managing chronic pain. If proven to be safe and effective, insular DBS will offer a much needed non-pharmacological treatment option for patients suffering from refractory chronic pain.

项目概要 难治性慢性疼痛患者通常对传统镇痛药或弱阿片类药物没有反应 因为这些药物不能直接解决引起疼痛的原因。许多慢性疼痛患者并不 即使采用循证治疗也能达到满意的疼痛缓解效果，或者他们不能耐受有效的治疗 由于不良副作用而服用的剂量。深部脑刺激（DBS）已经是一种成熟的技术 顽固性运动障碍和癫痫的治疗以及该领域的最新进展 疼痛神经生理学和生物技术可能会促进 DBS 作为非药物疗法的使用 治疗难治性慢性疼痛。 在该项目的第一阶段，我们将招募 12 名患有难治性神经病理性疼痛的受试者来研究 急性刺激和神经生理学脑岛脑绘图住院临床试验 监控。用于刺激和记录的电极将沿立体定向植入 岛叶皮质的前后轴。急性岛叶病期间具有积极镇痛作用的受试者 拟议项目第一阶段的刺激将继续到第二阶段，其中包括 慢性岛状疱疹的随机、假刺激对照、双盲、交叉临床试验 DBS 的目的是获得该手术的安全性和有效性数据。此外，我们的目标是 通过研究神经活动的变化来开发疼痛的神经生理学生物标志物。 从这项研究中获得的安全数据、效应大小和岛岛刺激参数将用于 后续临床试验的设计。该项目中确定的神经生理学疼痛生物标志物 还将有助于开发一种新颖的闭环岛状 DBS 系统，以及新的 管理慢性疼痛的诊断/预后措施。如果被证明是安全有效的，孤立的 星展银行将为患有以下疾病的患者提供急需的非药物治疗选择 难治性慢性疼痛。