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: 10159744
• 负责人: SHALENDER BHASIN
• 金额: $ 103.03万
• 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/10159744
• 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; 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; 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 outcomes; 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; rehabilitation research; 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25万名美国人因脊髓损伤（SCI）导致瘫痪而生活，这是最多的美国人之一 一个人一生中的悲剧事件。链接在多个生理器官系统中定义了SCI的人 有助于逐渐下降的肌肉骨骼和心脏代谢健康的恶性循环，以及 福利。认识到慢性SCI对个人健康的严重删除的影响 国家医学康复研究中心（NCMRR）认为“药物，刺激和 锻炼…改善SCI患者运动功能和健康的策略”研究的优先领域。 NCMRR进一步强调了多组分干预措施的效率试验，因为该应用程序提议 完成。有证据 - 大多来自非随机研究 - 手臂的测能和功能 腿部骑行期间下肢的电刺激（FES-LC）提高了SCI的身体能力 患者。但是，仅手臂或FES-LC实现的有氧需求和工作量通常是 没有足够的强度来诱导最佳的肌肉骨骼和代谢适应。 SCI与 雄激素缺乏症的高患病率进一步导致肌肉丧失，代谢失调和 情绪低落。通过将FES-LC与并发的ARM测能法（“混合”训练）相结合，高度更高 与仅在任何一种干预措施中都可以实现运动强度。混合练习对 雄激素给药增强了肌肉质量，力量和功能。此外，雄激素可能 在改善情绪，福祉，疼痛敏感性和代谢结果方面具有额外的有益作用。 我们假设一个基于家庭的多模式功能恢复和代谢健康增强 程序包括并发的FES-LC和ARM测能法，以及雄激素（19-北植物） decanoate，第19届）比单独的手臂在提高有氧运动能力，肌肉方面更有效 质量和力量，代谢健康，自我报告的功能和流动性以及福祉。这个假设将是 在SCI后6个月或更晚的6个月后，在84名C7至T12 SCI，AIS A，B或C的随机试验中进行了测试。 参与者将单独将其随机分配给多模式干预措施或单独的手臂测量法。 在运动实验室进行了2周的培训后，将在参与者的家中进行干预， 使用家庭锻炼的视频监控。主要结果是峰值有氧能力。次要结果 包括自我报告的功能和使用计算机化自适应测试版本的脊髓评估的机动性 伤害功能指数；肌肉质量，力量和疲劳性；脂肪质量和分布；代谢（胰岛素 灵敏度；脂质；炎症标记）；健康（情绪，焦虑，痛苦和生活满意度）。一个间 纪律团队，进入大型患者池，严格的试用设计，有助于注意患者安全和 统计能力以及包括基于绩效和患者报告的结果的统计能力应促进 拟议目的的实现，对改善SCI患者的护理具有影响。