Thoracic Neuromodulation for Diabetic Gastroparesis

胸神经调节治疗糖尿病胃轻瘫

• 批准号: 10504662
• 负责人: Braden Kuo
• 金额: $ 28.31万
• 依托单位: AUGUSTA UNIVERSITY
• 依托单位国家: 美国
• 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/10504662
• 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; Nausea and Vomiting; Neuropathy; Non-Insulin-Dependent Diabetes Mellitus; Outcome; Outcome Measure; Peripheral; Pilot Projects; Placebos; Primitive foregut structure; Process; Quality of life; Randomized; Randomized Controlled Trials; 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; Work; arm; autonomic reflex; base; cell motility; design; diabetes management; diabetic; 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; safety and feasibility; secondary outcome; source localization; symptomatic improvement

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.

项目摘要/摘要 糖尿病的全球发病率正在上升。胃轻瘫是糖尿病的重要并发症 这导致症状使人衰弱并影响生活质量。当前的治疗选择 糖尿病性胃轻瘫是有限的。明显的内脏传入神经病与 在1型和2型糖尿病的恶心中都可以看到糖尿病性胃轻瘫和交感神经过度活动 和糖尿病并发症。这些功能障碍可能是由影响胸腔的神经病引起的 带有一般内脏传入和gangionic交感神经的脊柱神经 在更大的ble症神经中，支配了前肢。胸椎的神经调节 神经应改善糖尿病性胃轻瘫症状并恢复生活质量 神经病和胃感觉运动功能。我们的实验室已经开发并完善了一部小说，非 - 侵入性，神经调节治疗，胸神经磁神经调节疗法 （thors-magnt）。在我们对糖尿病性胃轻瘫的成年人的不受控制的试验中，Thors-Magnt具有 表现出可行性，可接受性和DGP症状的改善。是否活动 神经调节比假疗法更好，最佳治疗频率不是 已知。我们建议进行剂量范围，假对照试验（PILOT NIH 1B） 评估thors-magnt对糖尿病症状严重程度和生活质量的影响 胃轻瘫（TNM-DGP试验）。我们将检验以下假设，即Thors-Magnt将改善 与假相比，内脏传入神经病，自主和胃功能障碍。我们也会 测试是否由于（a）（a）外围spino-gut轴的神经调节或（b）是否有任何改进 边缘系统和自主网络的中心结构，或两者兼有。成功完成 这项试点研究将为胃肉食疾病过程提供见解，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。我们的期望 结果包括开发新颖的，无创的，安全有效的糖尿病治疗 胃轻瘫。这些努力将在NIH 2阶段2试验中为未来的真实效力测试提供信息 多相优化策略（大多数）设计。