Multimodality Intervention to Improve Function and Metabolism in Spinal Cord Injury

多模式干预改善脊髓损伤的功能和代谢

• 批准号: 9767249
• 负责人: SHALENDER BHASIN
• 金额: $ 74万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-08-21 至 2023-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9767249
• 关键词: Achievement; Address; Aerobic; Age; American; Androgens; Anemia; Anxiety; Area; Attention; Autonomic Dysfunction; Body fat; Caring; Chronic; Clinical Trials Design; Decanoates; Ergometry; Event; Exercise; Exercise Therapy; FPS-FES Oncogene; Fatty acid glycerol esters; Female; Health; High Prevalence; Home environment; Hormones; Hybrids; Impairment; Individual; Inflammation; Injections; Injury; Insulin Resistance; Intervention; Leg; Life; Link; Lipids; Lower Extremity; Medical center; Metabolic; Metabolism; Modality; Monitor; Moods; Morbidity - disease rate; Muscle; Muscle function; Muscular Atrophy; Musculoskeletal; Nandrolone; Outcome; Pain; Paralysed; Participant; Patient Outcomes Assessments; Patient Self-Report; Patients; Performance; Personal Satisfaction; Persons; Pharmacologic Substance; Physical Capacity; Physical Exercise; Physical Function; Physiological; Placebos; Plasma; Public Health; Quality Control; Quality of life; Randomized; Recovery of Function; Rehabilitation Research; Reporting; Research; Spinal cord injury; Spinal cord injury patients; Supervision; Telephone; Testing; Training; Visceral fat; Visiting Nurse; Workload; arm; base; body system; cardiometabolism; computerized; efficacy trial; exercise intensity; exercise intervention; fasting glucose; functional electrical stimulation; improved; improved functioning; indexing; inflammatory marker; insulin sensitivity; laboratory experiment; lean body mass; male; men; mortality; motor function improvement; multi-component intervention; multimodality; muscle form; muscle strength; neuromuscular stimulation; pain sensitivity; patient safety; primary outcome; programs; randomized trial; response; satisfaction; secondary outcome; selective androgen receptor modulator; sex; treatment arm; trial design

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.

超过250，000名美国人生活在脊髓损伤（SCI）导致的瘫痪中，这是最常见的脊髓损伤之一。 一个人生命中的悲惨事件。SCI患者多个生理器官系统的相互关联缺陷 导致肌肉骨骼和心脏代谢健康逐渐下降的恶性循环， 幸福认识到慢性SCI对个人健康的严重有害影响， 国家医疗康复研究中心（NCMRR）认为“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。的 NCMRR进一步强调了多组分干预措施的有效性试验，因为该申请建议 完成。有证据--大部分来自非随机研究--表明手臂测力和功能 下肢电刺激可改善SCI患者的体能 患者然而，通过手臂测力计或FES-LC单独实现的有氧需求和工作负荷通常是不合适的。 强度不足以诱导最佳的肌肉骨骼和代谢适应。SCI与 雄激素缺乏症的高患病率，这进一步导致肌肉损失，代谢失调， 情绪低落通过将FES-LC与同时进行的手臂测力计（“混合”训练）相结合， 的运动强度可以达到比单独干预。混合运动对 肌肉质量、力量和功能通过雄激素给药而增强。此外，雄激素可能 在改善情绪、健康、疼痛敏感性和代谢结果方面具有额外的有益效果。 我们假设，以家庭为基础的多模态功能恢复和代谢健康增强 包括同步FES-LC和臂测力计以及雄激素（19-去甲睾酮）的计划 癸酸，19 ND）在改善有氧能力、肌肉 质量和力量，代谢健康，自我报告的功能和流动性，以及幸福。这一假设将是 在84名C7至T12 SCI患者中进行了随机试验，AIS分级为A、B或C，SCI后6个月或更长时间。 受试者将被随机分配至多模态干预或手臂测力计，持续16周。 在运动实验室训练2周后，干预将在参与者家中进行， 使用视频监控家庭锻炼。主要结果是峰值有氧能力。次要结局 包括自我报告功能和使用计算机化的脊髓自适应测试版本评估的活动性 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 敏感性;脂质;炎症标志物）;幸福感（情绪，焦虑，疼痛和生活满意度）。一个间- 学科团队，访问大型患者库，严格的试验设计，对患者安全的不懈关注， 统计功效以及纳入基于性能和患者报告的结局应有助于 这些目标的实现对改善SCI患者的护理具有重要意义。