Optimizing Technology and Treatment for Non Specific Chronic Low Back Pain

专有：本提案包含Highland Instruments的商业机密和其他专有或机密信息，仅供美国国立卫生研究院（NIH）用于评估本SBIR提案。不授予其他权利。这一建议和 未经Highland Instrument的许可，不得在NIH之外披露本文所包含的商业秘密和其他专有或机密信息的全部或部分内容。这一限制并不限制NIH使用数据中包含的信息的权利，如果这些信息是从以下来源获得的： 另一个来源没有限制。本图例适用于整个提案，包括但不限于本提案的摘要、引言、具体目标、研究计划（所有组成部分）、商业化计划和人类受试者部分。 抽象的。慢性腰痛（CLBP）是疼痛和残疾的主要原因[1-5]。非特异性下 疼痛（即，[3]最常见的是背部疼痛[4]。目前的治疗方法[4，6-12] 没有直接解决疼痛感觉在大脑中处理的事实[4，6，7]，即使是非特异性的 慢性下腰痛（NSCLBP）病理学可与慢性疼痛引起的大脑变化相关 结构与功能[13-21]非侵入性脑刺激（NIBS）已成功应用于 治疗某些疾病状态下的慢性疼痛，其中治疗引起的大脑活动变化恢复 与慢性疼痛的感知/感觉相关的适应不良可塑性[14，15，22]。不过最 常见NIBS方法，经颅磁刺激（TMS）和经颅直流电刺激 （tDCS）在治疗NSCLBP中显示出有限的（如果有的话）功效[23-28]。.据推测， 在这些技术中，聚焦性、穿透性和靶向控制限制了它们的治疗功效[29-33]。 超声电刺激（ESStim™）是一种改进的NIBS模式，克服了其他方法的局限性。 通过结合独立控制的电磁场和超声波场， 刺激电流通过调谐机电耦合在神经组织。该提案的重点是 评估我们的非侵入性ESStim系统是否可以有效治疗NSCLBP。第一阶段，评估 建议工作的可行性，我们将在给予固定剂量的ESStim后随访20名NSCLBP患者， 10天，20分钟/天，持续两周（10个假ESStim，10个ESStim）。我们将评估一组 安全性、疼痛、定量感觉测试（QST）、功能和整体心理社会自我评估 患者，在治疗期间和末次治疗后至少6周进行评价。 接下来在II期，我们将在给予固定剂量的地塞米松后随访40名NSCLBP患者（20名ESStim，20名SHAM）。 刺激10天，20分钟/天，持续两周时间，然后是三周的双周刺激， 20分钟/天（共16次刺激）。我们将对这些患者进行相同的评估 在第一阶段验证，并比较测试干预措施的有效性至少八周后， 最后一次治疗与NSCLBP治疗并行，我们将建立MRI衍生的模型， NSCLBP患者头部的刺激场（电场和声场模型），以计算 在大脑目标部位的刺激场特性。多元线性和广义线性回归 然后将建立模型并进行评估，以预测与疼痛、身体状况、 功能和心理社会评估作为基线疾病特征和基于MRI的 给药模型将结合计算工作，以开发优化的NSCLBP ESStim剂量 模型总的来说，我们假设所提出的实验，计算研究和技术 开发将使我们能够优化ESStim用于NSCLBP治疗。

Proprietary: This proposal includes trade secrets and other proprietary or confidential information of Highland Instruments and is being provided for use by the National Institutes of Health (NIH) for the sole purpose of evaluating this SBIR proposal. No other rights are conferred. This proposal and the trade secrets and other proprietary or confidential information contained herein shall further not be disclosed in whole or in parts, outside of NIH without Highland Instrument's permission. This restriction does not limit the NIH's right to use information contained in the data if it is obtained from another source without restriction. This legend applies to the entire proposal, including, but not limited to the Abstract, Introduction, Specific Aims, Research Plan (all components), Commercialization Plan, and Human Subject's Sections of this proposal. Abstract. Chronic low back pain (CLBP) is a leading cause of pain and disability[1-5]. Non-specific low back pain (i.e., without a known cause) is the most pervasive type of back pain [3]. Current therapies [4, 6-12] do not directly address the fact that pain sensation is processed in the brain [4, 6, 7] even though non-specific chronic low back pain (NSCLBP) symptomology can correlate with chronic pain induced changes in brain activity and/or structure [13-21]. 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 [14, 15, 22]. However, the most common NIBS methods, Transcranial Magnetic Stimulation (TMS) and Transcranial Direct Current Stimulation (tDCS), have shown limited, if any, efficacy in treating NSCLBP [23-28]. . It has been postulated that limitations in these techniques' focality, penetration, and targeting control limit their therapeutic efficacy [29-33]. 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. This proposal is focused on evaluating whether our noninvasive ESStim system can effectively treat NSCLBP. First in Phase I, to assess the feasibility of the proposed work, we will follow 20 NSCLBP patients after giving a fixed dose of ESStim for 10 days, 20 min/day, over a two-week period (10 SHAM ESStim, 10 ESStim). We will assess a battery of safety, pain, quantitative sensory testing (QST), function, and global psychosocial self-assessments 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 NSCLBP patients (20 ESStim, 20 SHAM) after giving a fixed dose of stimulation for 10 days, 20 min/day, over a two-week period, followed by three weeks of bi-weekly stimulation, 20 min/day (16 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 NSCLBP treatments, we will build MRI derived models of the stimulation fields in the heads (electric and acoustic field models) of the NSCLBP 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 NSCLBP 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 NSCLBP ESStim dosing model. Overall, we hypothesize that the proposed experiments, computational studies, and technology development will allow us to optimize ESStim for NSCLBP treatment.