Multimodality Intervention to Improve Function and Metabolism in Spinal Cord Injury

摘要 本行政补充申请要求批准延期一年， 资助，以使这项正在进行的随机试验，目前是在其第五年的资金完成。 这项资助的试验旨在检验一种假设，即一种包括混合运动加 睾酮和多个生理器官系统中的靶缺陷将更有效地改善 脊髓损伤患者的肌肉骨骼和代谢健康和幸福感。 在一项随机试验中，88名C7至T12 SCI患者，AIS A、B或C级，6 SCI后3个月或更长时间。参与者被随机分配到多模态干预或混合干预组。 运动加安慰剂16周，按年龄、性别和AIS分级分层。经过2周的培训， 运动实验室，干预是在参与者的家中进行，使用家庭视频监控 锻炼的主要结果是峰值有氧能力。次要结局包括自我报告的功能， 使用脊髓损伤功能指数的计算机化自适应测试版本评估活动性;肌肉 体重和力量;脂肪量和脂肪分布;胰岛素敏感性;脂质;炎症标志物;和健康 (mood焦虑、疼痛和生活满意度）。受资助试验的目的或设计没有改变。 在试验开始后不久，新冠肺炎疫情的突然爆发导致全国范围内关闭了 大多数非新冠肺炎临床研究活动。由于几年来临床研究的完全关闭， 2020年及2021年的临床研究活动缓慢增加，原因是 由于申请中讨论的因素，试验的招募受到了影响。尽管这些与COVID相关的 挑战，在过去一年中，试验的入组人数大幅增加，目前 入学率超过了最初的补助金申请中的预测。因此，父母以及 补充骨骼研究可望于明年完成。额外一年的部分支助 该项目的实施将有助于完成和结束审判，实现所有拟议目标， 该项目，以及国家卫生研究院在这一重要的高优先级项目上的慷慨投资的全部回报 给脊髓损伤患者 脊髓损伤（SCI）是最严重的疾病之一，极大地损害了一个人的行动能力，功能， 总体健康和福祉，并增加医疗保健资源利用和成本以及护理人员负担。 国家医疗康复研究中心已指定“药物，刺激， 运动.改善脊髓损伤患者运动功能和健康的策略”是优先研究领域。因为 多模式干预的所有组成部分都可以在市场上买到，这项创新试验的结果 完成后可以迅速转化为临床实践并改善健康， SCI患者的健康。

Abstract This application for an administrative supplement requests approval for a one-year extension with partial funding to enable the completion of this ongoing randomized trial that is currently in its fifth year of funding. The funded trial aims to test the hypothesis that a multi-modality intervention that includes hybrid exercise plus testosterone and targets deficits in multiple physiologic organ systems will be more efficacious in improving musculoskeletal and metabolic health and wellbeing of people living with SCI than hybrid excise plus placebo. This hypothesis is being tested in a randomized trial in 88 persons with C7 to T12 SCI, AIS grade A, B or C, 6 months or later after SCI. Participants are being randomized to either the multi-modality intervention or hybrid exercise plus placebo for 16 weeks, stratified by age, sex, and AIS grade. After 2-weeks of training in the exercise laboratory, the intervention is 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 and strength; fat mass and fat distribution; insulin sensitivity; lipids; inflammatory markers; and wellbeing (mood, anxiety, pain, and life satisfaction). The aims or the design of the funded trial have not changed. Very shortly after the trial's initiation, the sudden onset of the COVID pandemic led to nationwide shutdown of most non-covid clinical research activities. Due to the complete shutdown of clinical research for several months in 2022 followed by slow ramp up of clinical research activities in 2020 and 2021 due to multitude of factors that are discussed in the application, the enrollment in the trial suffered. In spite of these COVID-related challenges, the enrollment in the trial during the past year has increased substantially and the current enrollment rate exceeds that projected in the original grant application. Therefore, the parent as well as the supplemental bone study are on target for completion in the coming year. An additional year of partial support of the project would enable completion and close-out of the trial, accomplishment of all the proposed aims of the project, and accrual of full returns on the NIH's generous investment in this important project of high priority to people living with a SCI. Spinal cord injury (SCI) is one of the most grievous conditions that greatly impairs a person's mobility, function, overall health, and wellbeing, and increases healthcare resource utilization and costs and caregiver burden. The National Center for Medical Rehabilitation research has designated “pharmaceutical, stimulation, and exercise…strategies to improve motor function and health of SCI patients” a priority area of research. Because all components of the multimodality intervention are commercially available, the findings of this innovative trial upon its completion could be expeditiously translated into clinical practice and improve the health and wellbeing of people with SCI.