Multimodality Intervention to Improve Function and Metabolism in Spinal Cord Injury

摘要 此行政补充申请请求批准延期一年，部分延期 提供资金，以便能够完成这项正在进行的随机试验，目前该试验已进入供资的第五个年头。 这项由基金资助的试验旨在检验这样一种假设，即包括混合运动在内的多模式干预 多个生理器官系统中的睾酮和靶缺陷将更有效地改善 与混合运动加安慰剂相比，脊髓损伤患者的肌肉骨骼和代谢健康及幸福感。 这一假设正在88名C7至T12脊髓损伤患者中进行随机试验，AIS A、B或C级，6 在脊髓损伤后几个月或更晚。参与者被随机分为多模式干预或混合干预 运动加安慰剂16周，按年龄、性别和AIS等级分层。在经过两周的培训后， 运动实验室，干预在参与者的家中进行，使用家庭的视频监控 锻炼身体。主要结果是最大有氧能力。次要结果包括自我报告的功能和 用计算机化自适应测试版本的脊髓损伤-肌肉功能指数评估活动能力 质量和强度；脂肪质量和脂肪分布；胰岛素敏感性；血脂；炎症标记物；和健康 (情绪、焦虑、痛苦和生活满意度)。这项资助试验的目的或设计没有改变。 试验开始后不久，COVID大流行的突然爆发导致全国范围内关闭了 大多数非临床研究活动。由于几项临床研究完全停止 2022年和2021年临床研究活动缓慢增长，原因是 在申请中讨论的因素，招生试验受到了影响。尽管存在这些与COVID相关 挑战，过去一年中参加试验的人数大幅增加，目前 入学率超过了最初拨款申请中预计的数字。因此，父母以及 补充骨骼研究正在按目标在来年完成。额外一年的部分支持 该项目将能够完成和结束试验，实现所有拟议的目标 该项目，以及美国国立卫生研究院对这一高度优先的重要项目的慷慨投资所产生的全部回报 带着SCI生活的人。 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， 整体健康和福祉，并增加医疗资源利用率、成本和照顾者负担。 国家医疗康复研究中心已将“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。因为 多模式干预的所有组件都可以在商业上获得，这是这项创新试验的发现 建成后可迅速转化为临床实践，改善健康和 脊髓损伤患者的健康状况。

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.