Multimodality Intervention to Improve Function and Metabolism in Spinal Cord Injury

超过25万美国人生活在由脊髓损伤(SCI)导致的瘫痪中，脊髓损伤是 一个人生活中的不幸事件。脊髓损伤患者多个生理器官系统的连锁缺陷 造成肌肉骨骼和心脏代谢健康逐渐下降的恶性循环，以及 幸福。认识到慢性脊髓损伤对个人健康的深远有害影响， 美国国家医疗康复研究中心(NCMRR)认为“药物、刺激和 练习…改善脊髓损伤患者运动功能和健康的策略“是优先研究的领域。这个 NCMRR进一步强调了多成分干预的有效性试验，因为本申请建议 完成任务。有证据表明--主要来自非随机研究--手臂测力和功能 腿部电刺激(FES-LC)改善脊髓损伤大鼠的体能 病人。然而，仅通过ARM测功仪或FES-LC实现的有氧需求和工作负荷通常是 没有足够的强度来诱导最佳的肌肉骨骼和代谢适应。SCI与 雄激素缺乏的高患病率，这进一步导致肌肉损失、代谢失调以及 情绪低落。通过将FES-LC与同时进行的手臂测功术(“混合”训练)相结合，大大提高了水平 运动强度的降低比单独进行任何一种干预都要好。混合运动对大鼠心脏功能的影响 注射雄激素可以增加肌肉质量、力量和功能。此外，雄激素可能 在改善情绪、幸福感、疼痛敏感度和代谢结果方面有额外的有益效果。 我们假设以家庭为基础的多通道功能恢复和代谢健康增强 该计划包括同时进行FES-LC和ARM测功术，以及雄激素(19-去甲睾酮 在改善有氧能力、肌肉等方面比单纯手臂测功术更有效。 质量和力量、新陈代谢健康、自我报告的功能和机动性，以及幸福感。这一假设将是 在一项随机试验中对84名脊髓损伤后6个月或以后的C7至T12脊髓损伤患者进行了测试。 参与者将被随机接受多模式干预或仅进行手臂测功术，为期16周。 在运动实验室进行为期两周的训练后，干预将在参与者的家中进行， 采用视频监控的方式进行居家锻炼。主要结果是最大有氧能力。次要结果 包括使用计算机化脊髓适应性测试版本评估自我报告功能和活动能力 损伤功能指数；肌肉质量、力量和疲劳性；脂肪质量和分布；代谢(胰岛素 敏感度；血脂；炎症标志物)；幸福感(情绪、焦虑、疼痛和生活满意度)。一位内部人士- 纪律团队，接触到大量的患者池，严格的试验设计，勤奋地关注患者安全和 统计能力，以及纳入基于绩效和患者报告的结果，应有助于 实现拟议的目标，这对改善脊髓损伤患者的护理具有重要意义。

Over 250,000 Americans are living with paralysis resulting from spinal cord injury (SCI), one of the most grievous events in a person's life. Inter-linked deficits in multiple physiologic organ systems in persons with SCI contribute to a vicious cycle of progressively declining musculoskeletal and cardiometabolic health, and wellbeing. In recognition of the profoundly deleterious effects of chronic SCI on an individual's health, the National Center for Medical Rehabilitation Research (NCMRR) has deemed “pharmaceutical, stimulation, and exercise…strategies to improve the motor function and health of SCI patients” a priority area of research. The NCMRR has further emphasized efficacy trials of multicomponent interventions, as this application proposes to accomplish. There is evidence - mostly from nonrandomized studies - that arm ergometry and functional electrical stimulation of the lower extremity during leg cycling (FES-LC) improve physical capacity of SCI patients. However, the aerobic demands and workloads achieved by arm ergometry or FES-LC alone are often not of sufficient intensity to induce optimal musculoskeletal and metabolic adaptations. SCI is associated with high prevalence of androgen deficiency, which further contributes to muscle loss, metabolic dysregulation, and low mood. By combining FES-LC with concurrent arm ergometry (“hybrid” training), substantially higher levels of exercise intensity can be achieved than with either intervention alone. The effects of hybrid exercise on muscle mass, strength, and function are augmented by androgen administration. Furthermore, androgen may have additional beneficial effects in improving mood, wellbeing, pain sensitivity, and metabolic outcomes. We hypothesize that a Home-Based Multimodality Functional Recovery and Metabolic Health Enhancement Program that includes concurrent FES-LC and arm ergometry, and an androgen (19-nortestosterone decanoate, 19ND) would be more efficacious than arm ergometry alone in improving aerobic capacity, muscle mass and strength, metabolic health, self-reported function and mobility, and wellbeing. This hypothesis will be tested in a randomized trial in 84 persons with C7 to T12 SCI, AIS grade A, B or C, 6 months or later after SCI. Participants will be randomized to either the multi-modality intervention or arm ergometry alone for 16 weeks. After 2-weeks of training in the exercise laboratory, the intervention will be conducted in the participant's home, using video monitoring of the home exercise. Primary outcome is peak aerobic capacity. Secondary outcomes include self-reported function and mobility assessed using computerized adaptive test version of Spinal Cord Injury-Functional Index; muscle mass, strength and fatigability; fat mass and distribution; metabolism (insulin sensitivity; lipids; inflammatory markers); wellbeing (mood, anxiety, pain, and life satisfaction). An inter- disciplinary team, access to a large patient pool, rigorous trial design, assiduous attention to patient safety and statistical power, and inclusion of performance-based and patient-reported outcomes should facilitate the accomplishment of the proposed aims, which have implications for improving the care of SCI patients.