Transformation of Dormant Spinal Networks to Mitigate Symptoms of Neurogenic Bladder

转变休眠脊柱网络以减轻神经源性膀胱的症状

• 批准号: 10325406
• 负责人: Parag Gad
• 金额: $ 95.64万
• 依托单位: SPINEX, INC.
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-15 至 2023-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10325406
• 关键词: Agonist; Anti-Cholinergics; Attention; Awareness; Bladder; Bladder Control; Botulinum Toxins; Brain; Caring; Catheters; Chronic; Clinical; Clinical Research; Clinical Trials; Communication; Conscious; Data; Data Engineering; Dependence; Devices; Engineering; Ensure; Esthesia; Functional disorder; Future; Goals; Home; Impairment; Incontinence; Individual; Injections; Lead; Lower Extremity; Lower urinary tract; Mediating; Modality; Motor; Multiple Sclerosis; Nerve; Nerve Fibers; Nervous System Trauma; Neurogenic Bladder; Neurologic; Neuronal Plasticity; Neurostimulation procedures of spinal cord tissue; Organ; Overactive Bladder; Paralysed; Parkinson Disease; Patients; Pharmaceutical Preparations; Phase; Physiologic pulse; Physiological; Placebos; Plant Roots; Play; Posterior Tibial Nerves; Procedures; Quality of life; Questionnaires; Randomized; Recovery; Recurrence; Reporting; Research; Research Design; Risk; Risk Management; Rogaine; Role; Safety; Sensory; Signal Transduction; Spinal; Spinal Cord; Spinal cord injury; Spinal cord injury patients; Stroke; Symptoms; Techniques; Technology; Testing; Time; Upper Extremity; Urinary Incontinence; Urinary tract infection; Urodynamics; Visit; Volition; Work; base; clinically significant; control trial; cost; design; experience; functional restoration; impression; improved; injured; micturition urgency; motor rehabilitation; neural circuit; neural network; neuroregulation; novel strategies; novel therapeutics; partial recovery; patient population; pressure; prevent; primary endpoint; primary outcome; prototype; recruit; relating to nervous system; restoration; side effect; urinary; validation studies; verification and validation; virtual

Summary Spinal cord injury invariably leads to severe dysfunction of the lower urinary tract; patients develop urinary incontinence, recurrent urinary tract infections, incomplete bladder emptying and high bladder pressures. Reliance on catheters to empty the bladder is virtually universal. Established therapies for lower urinary tract dysfunction due to spinal cord injury focus on preventing and managing complications rather than on restoring function. Relying on our years of experience in rehabilitation of motor function after paralysis, we are confident that we can change the paradigm of bladder care in individuals with spinal cord injuries as well. Transcutaneous Electrical Spinal Cord Neuromodulation (TESCoN) offers a diametrically different approach to classic therapies for neurogenic bladder: by delivering low-intensity sub-motor threshold electrical pulses to the spinal cord, TESCoN activates lumbar neural networks rendered dysfunctional by the spinal cord injury and restores some communication between the lower urinary tract and higher neural centers responsible for micturition control. Results from our preliminary studies indicate that TESCoN-mediated neuromodulation improves bladder capacity, diminishes urinary incontinence and, remarkably, restores bladder sensation even in individuals, whose spinal cord injury is considered clinically complete. In this Phase II application, we propose to build a commercial version of the TESCoN prototype under design controls and use the device in a clinical validation study. We propose a multicenter randomized control trial to demonstrate the beneficial effects of TESCoN on the paralyzed lower urinary tract. By recruiting sixty individuals with spinal cord injury and comparing the effects of sham and true stimulation on their lower urinary tract, we aim to show that TESCoN has a significant role in managing and rehabilitating urinary function in the clinical setting (primary outcome). The academic roots of our company and the team we have assembled (engineers, entrepreneurs and clinicians) ensure that our study design, implementation and analysis will be both impactful and rigorous. Successful completion of this study will provide evidence for a FDA 510(k) submission. Finally, if TESCoN is successful in the case of a neurological impairment as devastating as a spinal cord injury, we are confident that we will be able to bring this technology to a much larger population of patients suffering from lower urinary tract dysfunction due to both neurological and non-neurological conditions, such as stroke, multiple sclerosis, Parkinson’s disease and idiopathic overactive bladder.

概括 脊髓损伤总是会导致严重的下泌尿道功能障碍； 尿失禁、反复尿路感染、膀胱排空不完全和膀胱压力高。 依赖导管排空膀胱几乎是普遍的下尿路治疗方法。 脊髓损伤引起的功能障碍的重点是预防和管理并发症，而不是恢复 凭借我们多年的瘫痪后运动功能康复经验，我们充满信心。 我们也可以改变脊髓损伤患者的膀胱护理模式。 脊髓电神经调节 (TESCoN) 提供了与经典疗法截然不同的方法 对于神经源性膀胱：通过向脊髓传递低强度亚运动阈值电脉冲， TESCoN 激活因脊髓损伤而功能失调的腰椎神经网络，并恢复一些功能 下泌尿道和负责排尿控制的高级神经中枢之间的通讯。 我们的初步研究结果表明 TESCoN 介导的神经调节可改善膀胱 容量，减少尿失禁，并且罕见地恢复膀胱感觉，甚至对于患有以下疾病的个体也能恢复膀胱感觉： 临床上认为脊髓损伤是完全性的。 在此第二阶段应用中，我们建议在下构建 TESCoN 原型的商业版本 设计对照并在临床验证研究中使用该设备。我们提出了多中心随机对照。 通过招募 60 名试验来证明 TESCoN 对瘫痪的下尿路的有益作用。 患有脊髓损伤的个体，并比较假刺激和真实刺激对其下尿路的影响 道，我们的目的是证明 TESCoN 在管理和恢复泌尿功能方面具有重要作用 临床环境（主要成果）。我们公司和我们组建的团队的学术根源。 （工程师、企业家和超级明星）确保我们的研究设计、实施和分析都将是 该研究的成功完成将为 FDA 510(k) 提交提供证据。 最后，如果 TESCoN 在治疗像脊髓损伤这样具有破坏性的神经损伤的情况下取得成功， 我们相信我们将能够将这项技术带给更多的患者 由于神经系统和非神经系统疾病（例如中风）导致的下尿路功能障碍， 多发性硬化症、帕金森病和特发性膀胱过度活动症。