Functional and histological changes to peripheral innervation following spinal cord stimulation in patients with painful diabetic neuropathy

疼痛性糖尿病神经病变患者脊髓刺激后周围神经支配的功能和组织学变化

• 批准号: 10837475
• 负责人: Brian Dalm
• 金额: $ 73.98万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-12 至 2028-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10837475
• 关键词: Accounting; Age; American; Ankle; Biometry; Biopsy; Blood; Blood Pressure; Body fat; Body mass index; Clinic; Clinic Visits; Clinical; Clinical Management; Data; Data Set; Dependence; Detection; Development; Devices; Diabetes Mellitus; Diabetic Neuralgia; Diabetic Neuropathies; Diabetic mouse; Diagnosis; Diagnostic Equipment; Diagnostic tests; Distal; Early Diagnosis; Electric Stimulation; Electromyography; FDA approved; Fiber; Glycosylated hemoglobin A; Goals; Growth; Heart Rate; Histologic; Human; Implant; Length; Link; Lipids; Location; Longitudinal Studies; Manufacturer; Measurement; Measures; Mechanics; Medical; Metabolic; Methods; Michigan; Natural regeneration; Needles; Nerve; Nerve Fibers; Nerve Regeneration; Nerve Tissue; Neural Conduction; Neurologist; Neuronal Plasticity; Neuropathy; Neurostimulation procedures of spinal cord tissue; Non-Insulin-Dependent Diabetes Mellitus; Operative Surgical Procedures; Opiate Addiction; Opioid Analgesics; Pain; Pain Measurement; Pain management; Patients; Peripheral; Peripheral Nerves; Peripheral Nervous System Diseases; Placebo Control Effect; Placebo Effect; Population; Prediabetes syndrome; Quality of life; Recovery; Research; Research Personnel; Risk; SF-36; Skin; Skin Tissue; Spinal; Spinal Cord; Spinal nerve structure; Stimulus; Subcutaneous Tissue; Surface; Surgeon; Testing; Thigh structure; Tissues; Validation; Vertebral column; Visit; Work; cohort; design; diabetic; diagnostic signature; effective therapy; fasting glucose; follow-up; foot; implantable device; implantation; improved; innovation; instrument; longitudinal dataset; machine learning algorithm; nerve supply; neuroregulation; neurotrophic factor; novel; novel therapeutic intervention; pain reduction; pain score; painful neuropathy; preimplantation; primary endpoint; screening; secondary endpoint; sex; timeline; treatment group

PROJECT ABSTRACT Diabetes is the most common cause of peripheral neuropathy, a condition that impacts over 30 million Americans. Often, this condition occurs as painful diabetic peripheral neuropathy (PDPN), which is particularly challenging to treat in the clinic, in part due to the lack of effective treatments and the risk of dependency for opioid analgesics. Spinal cord stimulation (SCS) is a treatment that stimulates nerve electrical activity in the spine, and is proven to be effective for pain conditions, including PDPN, for which SCS is now FDA approved through multiple device manufacturers. However, the mechanisms by which SCS improves pain are not yet known, and may involve promoting neural plasticity and small fiber nerve regeneration. We hypothesize that the electrical activity in stimulated spinal nerves with SCS treatment improves pain due to, or in parallel to, improvements in peripheral tissue innervation. This is based on decades of research evidence that electrical stimulation can promote nerve plasticity and regeneration. We will compare 3 PDPN treatment groups (N=15 each) across an 18mo longitudinal study: conventional medical management (CMM), SCS treatment, or SCS with a delayed activation of the device at 3mo post-surgery (to control for placebo effect of the surgery or device implantation). A team comprised of neuroscientists, neurologists, a neuromodulation surgeon, and computational/biostatistical experts will collect an 8-point dataset across this study timeline, in order to rigorously compare pain improvement scores with small and large fiber neuropathy assessments, quality of life scores, and metabolic parameters. The innovation of this study is further driven by the inclusion of a new functional measure of small fiber nerve electrical activity, using the Detecting Early Neuropathy (DEN) device, which employs a microneedle array to collect data on nerve activity up to 4mm deep from the skin surface. This is the first device capable of measuring small nerve fiber activity as a diagnostic test for small fiber peripheral neuropathy, such as diabetic neuropathy. Taken together, this study will provide important new data on PDPN improvements with SCS treatment and whether mechanisms include changes to small fiber tissue innervation or nerve activity.

项目摘要 糖尿病是导致周围神经病变的最常见原因，这种疾病影响了3000多万美国人。 这种情况通常以疼痛的糖尿病周围神经病变(PDPN)的形式出现，这特别具有挑战性 由于缺乏有效的治疗和对阿片类镇痛剂的依赖风险，在临床上无法进行治疗。 脊髓刺激(Scs)是一种刺激脊柱神经电活动的治疗方法，已被证实。 对疼痛情况有效，包括PDPN，SCS现在通过多种设备获得FDA批准 制造商。然而，SCS改善疼痛的机制尚不清楚，可能涉及 促进神经可塑性和小纤维神经再生。我们假设大脑中的电活动 SCS刺激脊神经治疗可改善因周围改善引起的疼痛或同时改善疼痛 组织神经支配。这是基于数十年的研究证据，即电刺激可以促进神经 可塑性和再生能力。我们将比较3个PDPN治疗组(每个组15个)在18mo的纵向 研究：传统医疗管理(CMM)、SCS治疗或延迟激活设备的SCS 术后3mo(对照手术或植入物的安慰剂效应)。由以下人员组成的团队 神经学家、神经学家、神经调节外科医生和计算/生物统计学专家将收集 这项研究时间线上的8分数据集，以便严格比较疼痛改善评分与 以及大纤维神经病评估、生活质量评分和代谢参数。它的创新之处在于 进一步的研究是由于纳入了一种新的小纤维神经电活动的功能测量，使用 早期神经病(DEN)检测装置，采用微针阵列收集神经数据 活动距离皮肤表面达4毫米。这是第一个能够测量细小神经纤维的设备。 作为小纤维周围神经病变的诊断试验，如糖尿病神经病变。加在一起， 这项研究将为SCS治疗改善PDPN及其机制提供重要的新数据 包括小纤维组织神经支配或神经活动的改变。