Oxandrolone and Exercise: A potent therapy in the rehabilitation from burns

氧雄龙和运动：烧伤康复的有效疗法

• 批准号: 9212740
• 负责人: Oscar E. Suman-Vejas
• 金额: $ 58.05万
• 依托单位: UNIVERSITY OF TEXAS MED BR GALVESTON
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-08-01 至 2020-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9212740
• 关键词: 21 year old; Acquired Immunodeficiency Syndrome; Admission activity; Aerobic; Aging; Attenuated; Biochemical; Body Surface Area; Burn injury; Cachexia; Cardiopulmonary; Cardiovascular Physiology; Cardiovascular system; Caring; Catabolism; Child; Chronic; Cicatrix; Clinical; Combined Modality Therapy; Data; Disease; Dose; Equilibrium; Ethics; Exercise; Exercise Therapy; Foundations; Goals; Growth; Habilitation; Hospitals; Immunity; Immunosuppression; Inflammation; Inflammatory; Intervention; Liquid substance; Liver; Malignant Neoplasms; Mediating; Metabolic; Metabolism; Mission; Muscle function; Muscular Atrophy; Myopathy; National Institute of Child Health and Human Development; Obesity; Oral; Outcome; Oxandrolone; Pathologic; Patients; Pediatric Hospitals; Pharmaceutical Preparations; Physiological; Placebos; Population; Proteins; Quality of life; Randomized; Recovery; Rehabilitation therapy; Reporting; Research; Research Design; Resources; Skin; Testing; Testosterone; Therapeutic; Therapeutic Intervention; Therapeutic Uses; Thinness; Time; Tissues; Treatment Efficacy; Turner' s Syndrome; analog; base; bone loss; clinically relevant; endurance exercise; evidence base; exercise program; exercise training; experience; functional outcomes; hemodynamics; improved; injured; insulin sensitivity; lean body mass; muscle form; muscle strength; novel strategies; novel therapeutic intervention; novel therapeutics; pediatric burn injury; programs; prospective; public health relevance; pulmonary function; response; treatment strategy; wasting

 DESCRIPTION (provided by applicant): Children with severe burns manifest a catabolic state up to two years after burn. This catabolic state results in significant muscle wasting, weakness, immunosuppression, chronic bone loss, decreased growth, and concurs- rent increases in metabolic, hemodynamic, inflammatory, and scarring responses. In burned children, exercise training improves lean body mass (LBM), muscle strength, and cardiovascular endurance, though it does not restore these parameters to levels seen in healthy children. Similar improvements have been reported in burned children receiving oxandrolone, an oral synthetic testosterone analogue. In a preliminary study by the PI, the combination of exercise and oxandrolone eased burn-induced catabolism to a greater degree than ei- ther exercise or oxandrolone alone. Thus, the objective of this project is to compare the therapeutic and func- tional efficacy of the combined exercise-oxandrolone therapy with that of exercise alone, our current standard of burn care (SOC). The central hypothesis to be tested is that the combined exercise-oxandrolone therapy will be superior to exercise alone in attenuating burn-induced catabolism and increasing LBM, exercise endurance, and cardiovascular function. To this end, 100 severely burned children (7 to <21 years; burns e30% of the total body surface area) will be prospectively randomized to receive liquid oxandrolone (0.2 mg/kg/day, N=50) or placebo (N=50). Drug or placebo will be administered from hospital admission to the end of a 12-week exer- cise program (aerobic and resistive exercise), which will begin at hospital discharge. Two Specific Aims will be simultaneously pursued. Aim 1 will determine the physiological therapeutic efficacy of exercise train- ing/rehabilitation plus oxandrolone relative to that of exercise alone. The working hypothesis is that the combined therapy will be superior to exercise alone in improving LBM, muscle function, and overall cardiovas- cular function-all clinically relevant and vital functional endpoints. Aim 2 will determine the biochemical consequences of exercise training/rehabilitation plus oxandrolone relative to those of exercise alone. The working hypothesis is that the combined therapy will be superior to exercise alone in increasing protein balance, improving insulin sensitivity, and decreasing liver/tissue adiposity. This project is expected to estab- lish a new therapeutic approach that delivers more substantial improvements in the clinical and functional out- comes of burn-induced catabolism. It is also expected to provide a foundation for similar treatments in other muscle-wasting or muscle loss disorders. The long-term goal in this project is to identify clinically-effective, therapeutic interventions i the rehabilitation and recovery of severely burned children and NICHD's mission of improving rehabilitation of injured children so that they can fulfill their potential to live healthy productve lives.

 描述（由申请人提供）：严重烧伤的儿童在烧伤后两年内会出现分解代谢状态。这种分解代谢状态导致显着的肌肉萎缩、虚弱、免疫抑制、慢性骨质流失、生长下降，以及代谢、血流动力学、炎症和疤痕反应的同时增加。对于烧伤儿童，运动训练可以改善瘦体重（LBM）、肌肉力量和心血管耐力，但不能将这些参数恢复到健康儿童的水平。据报道，接受口服合成睾酮类似物氧雄龙的烧伤儿童也有类似的改善。在 PI 的一项初步研究中，运动和氧甲氢龙的结合比单独运动或氧甲氢龙更大程度地缓解了烧伤引起的分解代谢。因此，该项目的目的是比较运动-氧雄龙联合疗法与单独运动（我们目前的烧伤护理标准（SOC））的治疗和功能功效。要测试的中心假设是，运动与氧甲氢龙联合疗法在减轻烧伤引起的分解代谢和增加 LBM、运动耐力和心血管功能方面优于单独运动。为此，100 名严重烧伤儿童（7 岁至 <21 岁；烧伤占全身表面积的 30%）将前瞻性随机接受液体氧雄龙（0.2 毫克/公斤/天，N=50）或安慰剂（N=50）。从入院到出院时开始的 12 周锻炼计划（有氧运动和抗阻运动）结束，将使用药物或安慰剂。将同时追求两个具体目标。目标 1 将确定运动训练/康复加氧甲氢龙相对于单独运动的生理治疗功效。 目前的假设是，在改善 LBM、肌肉功能和整体心血管功能（所有临床相关且重要的功能终点）方面，​​联合疗法将优于单独运动。目标 2 将确定运动训练/康复加氧甲氢龙相对于单独运动的生化后果。目前的假设是，联合疗法在增加蛋白质平衡、改善胰岛素敏感性和减少肝脏/组织肥胖方面优于单独运动。该项目预计将建立一种新的治疗方法，为烧伤引起的分解代谢的临床和功能结果带来更实质性的改善。它还有望为其他肌肉萎缩或肌肉损失疾病的类似治疗奠定基础。该项目的长期目标是确定临床有效的治疗干预措施，以促进严重烧伤儿童的康复和恢复，以及 NICHD 的使命是改善受伤儿童的康复，使他们能够发挥潜力，过上健康、富有成效的生活。