Optimization of Non Invasive Brain Stimulation for Diabetic Neuropathic Pain

无创脑刺激治疗糖尿病神经病理性疼痛的优化

基本信息

批准号：
10316269
负责人：
Laura Dipietro
金额：
$ 40.51万
依托单位：
HIGHLAND INSTRUMENTS, INC.
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-12-10 至 2024-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10316269
关键词：
Acoustics Address Aftercare American Area Behavior Biophysics Brain Brief Pain Inventory Characteristics Clinic Clinical Complications of Diabetes Mellitus Coupling Development Diabetes Mellitus Disease Dose Double-Blind Method Effectiveness Electromagnetics Electrophysiology (science)Equilibrium Equipment and supply inventories Esthesia Foundations Head Health Surveys Home Injury Intervention Knee Osteoarthritis Linear Regressions Magnetic Resonance Imaging Measures Methods Modality Modeling Morbidity - disease rate Motor Motor Cortex Neurologic Neuropathy Pain Pain management Patient-Focused Outcomes Patients Penetration Perception Phase Physical Function Placebo Control Procedures Process Psychosocial Assessment and Care Quality of life Randomized SF-36 Safety Self Assessment Sensory Site Sleep Stratification Structure System Techniques Technology Testing Therapeutic Effect Tissues Transcranial magnetic stimulation Treatment Efficacy Ultrasonics United States Work actigraphy base behavioral study central pain chronic pain chronic pain management comparative efficacy computer studies diabetic diaries efficacy testing experimental study functional outcomes improved metabolic abnormality assessment mortality noninvasive brain stimulation novel outcome prediction overtreatment pain outcome pain patient pain reduction pain sensation pain symptom painful neuropathy prognostic psychosocial relating to nervous system safety assessment symptom treatment symptomatology technology development treatment duration vector

项目摘要

Abstract. Diabetic neuropathic pain (DNP) is one of the most common and difficult to treat complications of diabetes [1, 2]. Current therapies [3-10] do not directly address the fact that pain sensation is processed in the brain [10-13] and most act at the neuropathy site (i.e., in the periphery), although DNP patients also have a central pain component due to their injury [10-13]. DNP symptomatology correlates with chronic pain induced changes in brain activity and/or structure [13-19]. Non-Invasive Brain Stimulation (NIBS) has been successfully applied for the treatment of chronic pain in some disease states, where treatment induced changes in brain activity revert maladaptive plasticity associated with the perception/sensation of chronic pain [20-23]. However, the most common NIBS methods, Transcranial Magnetic Stimulation (TMS) and Transcranial Direct Current Stimulation (tDCS), have shown limited, if any, efficacy in treating neuropathic pain and DNP [12, 24-30]. It has been postulated that limitations in these techniques' focality, penetration, and targeting control limit their therapeutic efficacy [31-35]. Electrosonic Stimulation (ESStim™) is an improved NIBS modality that overcomes the limitations of other technologies by combining independently controlled electromagnetic and ultrasonic fields to focus and boost stimulation currents via tuned electromechanical coupling in neural tissue [36]. This proposal is focused on evaluating whether our noninvasive ESStim system can effectively treat DNP. First in Phase I, to assess the feasibility of the proposed work, we will follow 20 DNP patients after giving a fixed dose of ESStim for 5 consecutive days, 20 min/day (10 SHAM ESStim, 10 ESStim™). We will administer a battery of safety, pain, quantitative sensory testing (QST), motor function, and global self-assessments (e.g., QOL), and actigraphy measures in the patients, evaluated over the treatment period and for at least six weeks following the last treatment session. Next in Phase II, we will follow 40 DNP patients (20 ESStim, 20 SHAM) after giving a fixed dose of stimulation for 5 consecutive days, 20 min/day, followed by three weeks of bi- weekly stimulation, 20 min/day (11 total stimulations). We will evaluate these patients with the same battery of assessments validated in Phase I, and compare the efficacy of the tested interventions for at least eight weeks following the last treatment session. In parallel with the DNP treatments, we will build MRI derived models of the stimulation fields in the heads (electric and acoustic field models) of the DNP patients to calculate the stimulation field characteristics at the brain target sites. Multivariate linear and generalized linear regression models will then be built and evaluated to predict the DNP patient outcomes related to pain, physical function, and psychosocial assessments as a function of baseline disease characteristics and the MRI based dosing models. The computational work will be combined to develop an optimized DNP ESStim dosing model. Overall, we hypothesize that the proposed experiments, computational studies, and technology development will allow us to optimize ESStim™ for treatment of central pain in DNP.

【摘要】：糖尿病神经病理性疼痛(DNP)是糖尿病最常见且最难治疗的并发症之一。糖尿病 [1, 2] 目前的疗法 [3-10] 并未直接解决疼痛感觉是在大脑中进行处理的事实。大脑 [10-13] 并且大多数作用于神经病变部位（即外周），尽管 DNP 患者也有由于损伤导致的中枢疼痛成分 [10-13]。大脑活动和/或结构的改变[13-19]已成功进行。用于治疗某些疾病状态下的慢性疼痛，其中治疗会引起大脑变化活动恢复与慢性疼痛的感知/感觉相关的适应不良可塑性[20-23]。最常见的 NIBS 方法：经颅磁刺激 (TMS) 和经颅直流电刺激 (tDCS) 在治疗神经性疼痛和 DNP 方面的疗效即使有，也有限 [12, 24-30]。据推测，这些技术的焦点、穿透力和目标控制方面的局限性限制了它们的应用。治疗效果 [31-35] 电声刺激 (ESStim™) 是一种改进的 NIBS 方式，克服了这一问题。通过结合独立控制的电磁和超声波来克服其他技术的局限性通过神经组织中的调谐机电耦合来聚焦和增强刺激电流[36]。该提案的重点是评估我们的无创 ESStim 系统是否可以有效治疗 DNP。第一阶段，为了评估拟议工作的可行性，我们将在给予固定剂量后对 20 名 DNP 患者进行跟踪连续 5 天，20 分钟/天（10 个 SHAM ESStim，10 个 ESStim™）我们将管理电池。安全性、疼痛、定量感觉测试 (QST)、运动功能和整体自我评估（例如 QOL），和体动记录仪测量，在治疗期间和至少六周内进行评估在最后一次治疗后，我们将在第二阶段跟踪 40 名 DNP 患者（20 名 ESStim，20 名 SHAM）。连续 5 天、每天 20 分钟给予固定剂量的刺激，然后进行三周的双每周刺激，20 分钟/天（总共 11 次刺激）我们将使用相同的电池来评估这些患者。在第一阶段验证的评估，并比较测试干预措施至少八周的效果在最后一次治疗后，我们将与 DNP 治疗同时建立 MRI 衍生模型。 DNP 患者头部的刺激场（电场和声场模型）来计算大脑目标部位的刺激场特征。然后将建立并评估模型，以预测 DNP 患者与疼痛、身体功能、和心理社会评估作为基线疾病特征和基于 MRI 的剂量的函数总体而言，计算工作将被结合起来开发优化的 DNP ESStim 剂量模型。我们追求所提出的实验、计算研究和技术开发将允许我们优化 ESStim™ 以治疗 DNP 中的中枢性疼痛。