Thoracic Neuromodulation for Diabetic Gastroparesis

项目总结/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 导致衰弱症状并影响生活质量。的当前治疗选择 糖尿病胃轻瘫是有限的。严重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动见于恶心，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于神经病变影响胸部 携带一般内脏传入和节前交感传出的脊神经 在内脏大神经中，支配着前肠。胸椎神经调节 神经应该改善糖尿病胃轻瘫症状，并通过改善 神经病和胃感觉运动功能。我们的实验室已经开发和完善了一种新的，非- 侵入性，神经调节治疗，胸脊神经磁神经调节治疗 （ThorS-MagNT）。在我们对糖尿病胃轻瘫成人的非对照试验中，ThorS-MagNT 证明了DGP症状的可行性、可接受性和改善。无论是主动 神经调节比假治疗好，最佳治疗频率不是 知道的我们建议进行一项剂量范围、假对照试验（试点NIH Stage 1b）， 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将改善 内脏传入神经病变、自主神经和胃功能障碍。我们还将 测试任何改善是否归因于（a）外周脊肠轴或（B）的神经调节 边缘系统和自主神经网络的中央结构，或两者。成功完成 这项试验性研究将提供对胃轻瘫疾病过程的深入了解， 神经调节治疗在解决脑-肠轴破坏中的作用。我们预期的 结果包括开发一种新的、非侵入性的、安全有效的糖尿病治疗方法， 胃轻瘫这些努力将为未来NIH第2阶段试验中的真实疗效测试提供信息， 多阶段优化策略（MOST）设计。

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.