Optimizing Technology and Treatment for Non Specific Chronic Low Back Pain

专有：本建议书包括高地仪器的商业秘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建议书的目的。不授予任何其他权利。这项建议和 未经高地文书许可，不得在NIH以外的地方披露本文中包含的商业秘密和其他专有或机密信息的全部或部分。这一限制不限制NIH使用数据中包含的信息的权利，如果该信息是从 另一个不受限制的来源。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)、商业化计划和人类主体部分。 抽象的。慢性下腰痛(CLBP)是疼痛和残疾的主要原因[1-5]。非特指腰背部 疼痛(例如，原因不明)是最普遍的背部疼痛类型[3]。目前的疗法[4，6-12]做到了 没有直接解决这样一个事实，即痛感是在大脑中处理的[4，6，7]，即使不是特定的 慢性下腰痛(NSCLBP)的症状与慢性疼痛引起的脑部改变相关 活动和/或结构[13-21]。非侵入性脑刺激(NIBS)已成功地应用于 治疗某些疾病状态下的慢性疼痛，治疗引起的脑活动变化逆转 与慢性疼痛的知觉/感觉相关的适应不良可塑性[14，15，22]。然而，最多的 常用NIBS方法、经颅磁刺激(TMS)和经颅直流电刺激 (TDCs)，在治疗NSCLBP方面显示出有限的疗效[23-28]。。据推测，限制 在这些技术中，焦点、穿透和靶向控制限制了它们的治疗效果[29-33]。 电声刺激(ESSTim™)是一种改进的NIBS模式，它克服了其他 通过结合独立控制的电磁场和超声场来聚焦和增强技术 神经组织中通过可调谐机电耦合产生的刺激电流。这项提案的重点是 评估我们的非侵入性ESSTim系统是否可以有效地治疗NSCLBP。首先，在第一阶段，评估 建议工作的可行性，我们将跟踪20名NSCLBP患者在给予固定剂量的ESSTim治疗后 10天，每天20分钟，在两周内(10个假ESSTim，10个ESSTim)。我们将评估一系列 安全性、疼痛、定量感觉测试(QST)、功能和全球心理社会自我评估 在治疗期间和最后一次治疗后至少六周内对患者进行评估。 接下来，在第二阶段，我们将跟踪40名NSCLBP患者(20名ESSTim，20名Sham)，在给予固定剂量的 在两周内每天刺激10天，20分钟，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，并比较测试的干预措施在至少八周内的效果 最后一次治疗。在NSCLBP治疗的同时，我们将建立MRI衍生的 NSCLBP患者头部刺激场(电场和声场模型)的计算 脑靶部位刺激场特征。多元线性回归和广义线性回归 然后将建立和评估模型以预测NSCLBP患者与疼痛、身体状况相关的结果 功能，以及作为基线疾病特征和基于MRI的心理社会评估的函数 给药模型。计算工作将被结合起来，以开发优化的NSCLBP ESSTim剂量 模特。总体而言，我们假设拟议的实验、计算研究和技术 开发将使我们能够优化用于NSCLBP治疗的ESSTim。

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.