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 糖尿病是周围神经病变的最常见原因，这种疾病影响着超过 3000 万美国人。 通常，这种情况以疼痛的糖尿病周围神经病变 (PDPN) 的形式出现，这是特别具有挑战性的 无法在诊所进行治疗，部分原因是缺乏有效的治疗方法以及对阿片类镇痛药的依赖风险。 脊髓刺激 (SCS) 是一种刺激脊柱神经电活动的治疗方法，并且已被证明 对疼痛病症（包括 PDPN）有效，SCS 现已通过多种设备获得 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。我们假设电活动 通过 SCS 治疗刺激脊神经可改善疼痛，因为或同时改善外周神经 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 可塑性和再生性。我们将在 18 个月的纵向范围内比较 3 个 PDPN 治疗组（每组 N = 15） 研究：常规医疗管理 (CMM)、SCS 治疗或延迟激活设备的 SCS 术后 3 个月（以控制手术或装置植入的安慰剂效应）。一个团队由以下人员组成 神经科学家、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 本研究时间线内的 8 点数据集，以便严格比较疼痛改善分数与小 以及大纤维神经病评估、生活质量评分和代谢参数。本次的创新 该研究进一步推动了小纤维神经电活动的新功能测量，使用 检测早期神经病变 (DEN) 设备，采用微针阵列收集神经数据 活动深度可达距皮肤表面 4 毫米。这是第一个能够测量小神经纤维的设备 作为小纤维周围神经病变（例如糖尿病神经病变）的诊断测试的活性。综合起来， 这项研究将为 SCS 治疗改善 PDPN 以及机制是否有效提供重要的新数据 包括小纤维组织神经支配或神经活动的变化。