Thoracic Neuromodulation for Diabetic Gastroparesis

胸神经调节治疗糖尿病胃轻瘫

基本信息

批准号：
10661838
负责人：
Braden Kuo
金额：
$ 27.07万
依托单位：
AUGUSTA UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-07-15 至 2025-05-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10661838
关键词：
Abdominal Pain Address Adult Affect Autonomic Dysfunction Cardiovascular system Chest Complications of Diabetes Mellitus Development Diabetes Mellitus Disabled Persons Disease Dose Eating Esthesia Evoked Potentials Feeling Frequencies Functional Magnetic Resonance Imaging Functional disorder Funding Future Galvanic Skin Response Gastroparesis Goals Incidence Insula of Reil Insulin-Dependent Diabetes Mellitus Limbic System Magnetic Resonance Imaging Magnetism Measures National Institute of Diabetes and Digestive and Kidney Diseases Nausea Neuropathy Non-Insulin-Dependent Diabetes Mellitus Outcome Outcome Measure Peripheral Pilot Projects Placebos Primitive foregut structure Process Quality of life Randomized Randomized, Controlled Trials Safety Satiation Sensorimotor functions Sensory Severities Signal Transduction Spinal nerve structure Splanchnic Nerves Stimulus Stomach Structure Symptoms TNM Testing United States National Institutes of Health Visceral Afferents Vomiting Work arm autonomic reflex cell motility design diabetes management diabetic gastroparesis diaries disabling symptom effective therapy efficacious treatment efficacy testing gut-brain axis improved indexing insight multiphase optimization strategy neuroregulation novel primary outcome response secondary outcome source localization symptomatic improvement

项目摘要

Project Summary/Abstract The global incidence of diabetes is rising. Gastroparesis is a significant complication of diabetes that results in debilitating symptoms and affects quality of life. Current treatment options for diabetic gastroparesis are limited. Significant visceral afferent neuropathy is associated with diabetic gastroparesis and sympathetic overactivity is seen in nausea, both type 1 and 2 diabetes, and diabetic complications. These dysfunctions can result from neuropathy affecting the thoracic spinal nerves that carry both general visceral afferents and preganglionic sympathetic efferents in the greater splanchnic nerve, innervating the foregut. Neuromodulation of the thoracic spinal nerves should improve diabetic gastroparesis symptoms and restore quality of life by improving neuropathy and gastric sensori-motor function. Our lab has developed and refined a novel, non- invasive, neuromodulation treatment, Thoracic Spinal Nerve Magnetic Neuromodulation Therapy (ThorS-MagNT). In our uncontrolled trial of adults with diabetic gastroparesis, ThorS-MagNT has demonstrated feasibility, acceptability, and improvement of DGp symptoms. Whether active neuromodulation is better than sham therapy and the optimal frequency of treatment are not known. We propose to conduct a dose-ranging, sham-controlled trial (pilot NIH Stage 1b) to assess the effect of ThorS-MagNT on symptom severity and quality of life in diabetic gastroparesis (TNM-DGp Trial). We will test the hypothesis that ThorS-MagNT will improve visceral afferent neuropathy, autonomic and gastric dysfunction, compared to sham. We will also test whether any improvements are due to neuromodulation of (a) peripheral spino-gut axis or (b) central structures of the limbic system and autonomic network, or both. Successful completion of this pilot study will provide insights into gastroparesis disease processes and inform mechanisms of action of neuromodulation therapy in addressing disruption of the brain-gut axis. Our expected outcomes include development of a novel, non-invasive, safe and efficacious therapy for diabetic gastroparesis. These efforts will inform future true efficacy testing in an NIH Stage 2 trial using multiphase optimization strategy (MOST) design.

项目概要/摘要全球糖尿病发病率正在上升。胃轻瘫是糖尿病的重要并发症这会导致衰弱症状并影响生活质量。目前的治疗方案糖尿病性胃轻瘫是有限的。显着的内脏传入神经病变与糖尿病性胃轻瘫和交感神经过度活跃可见于恶心，1型和2型糖尿病，和糖尿病并发症。这些功能障碍可能是由影响胸部的神经病变引起的携带一般内脏传入神经和节前交感传出神经的脊神经位于内脏大神经中，支配前肠。胸椎的神经调节神经应通过改善糖尿病性胃轻瘫症状并恢复生活质量神经病变和胃感觉运动功能。我们的实验室开发并完善了一种新颖的、非侵入性神经调节治疗，胸椎神经磁神经调节治疗（雷神-MagNT）。在我们对患有糖尿病性胃轻瘫的成人进行的非对照试验中，ThorS-MagNT 证明了 DGp 症状的可行性、可接受性和改善。是否活跃神经调节优于假治疗，但最佳治疗频率并不相同已知。我们建议进行剂量范围、假手术对照试验（试点 NIH 1b 阶段）评估 ThorS-MagNT 对糖尿病患者症状严重程度和生活质量的影响胃轻瘫（TNM-DGp 试验）。我们将测试 ThorS-MagNT 将改进的假设与假手术相比，内脏传入神经病变、自主神经和胃功能障碍。我们也会测试任何改善是否归因于 (a) 外周脊髓肠轴或 (b) 的神经调节边缘系统和自主网络或两者的中央结构。顺利完成这项试点研究将深入了解胃轻瘫疾病的过程并为机制提供信息神经调节疗法在解决脑肠轴破坏方面的作用。我们的预期成果包括开发出一种新型、非侵入性、安全且有效的糖尿病疗法胃轻瘫。这些努力将为未来在 NIH 第 2 阶段试验中使用的真实功效测试提供信息多阶段优化策略（MOST）设计。