Protein Optimization with Exercise to Improve Muscle Mass and Functional Outcomes (PROXIMUS)

通过运动优化蛋白质以改善肌肉质量和功能结果 (PROXIMUS)

• 批准号: 10609050
• 负责人: SAPNA R KUDCHADKAR
• 金额: $ 34.46万
• 依托单位: BOSTON CHILDREN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-04-15 至 2025-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10609050
• 关键词: 1 year old; Acute; Adherence; Adverse effects; Adverse event; Age; Bed rest; Beds; Caring; Child; Childhood; Clinical; Clinical Trials; Cognitive; Computers; Country; Coupled; Creatinine; Critical Illness; Critically ill children; Data; Diet; Disability Evaluation; Disease; Dose; Enrollment; Equilibrium; Equipment and supply inventories; Equipoise; Exercise; Goals; Health; Image; Immobilization; Impairment; Incidence; Injury to Kidney; Intake; Intervention; Investigation; Measurement; Measures; Mechanical ventilation; Medical; Metabolic; Mission; Morbidity - disease rate; Muscle; Muscular Atrophy; National Institute of Diabetes and Digestive and Kidney Diseases; Nutrient; Nutritional Study; Outcome; Parenteral Nutrition; Patient-Focused Outcomes; Patients; Pediatric Intensive Care Units; Phase; Physical Exercise; Pilot Projects; Population; Proteins; Protocol Compliance; Protocols documentation; Public Health; Quality of life; Randomized; Randomized, Controlled Trials; Rehabilitation therapy; Reproducibility; Research Priority; Respiratory Failure; Safety; Serum; Severity of illness; Site; Stereotyping; Strategic Planning; Survivors; Testing; Thick; Time; United States National Institutes of Health; arm; exercise regimen; exercise rehabilitation; experience; functional outcomes; functional status; improved; innovation; lean body mass; mortality; muscle form; nutrition; open label; pilot trial; preservation; programs; psychologic; quadriceps muscle; randomized, clinical trials; response; safety and feasibility; screening; secondary analysis; secondary outcome; standard care; trial comparing; ultrasound

Mortality in U.S. pediatric intensive care units (PICUs) is improving, resulting in an increased focus on the quality of life of survivors who often have persistent physical, cognitive, and psychological impairments. Mechanically ventilated children in particular experience immobilization and poor nutrient intake, which results in muscle loss during acute illness. Early mobility and optimal nutrition during acute critical illness have been associated with muscle mass preservation and decreased duration of mechanical ventilation. These interventions may have the potential to decrease preventable PICU-acquired morbidities. However, the optimal doses and long-term benefits of these interventions have not been shown in randomized studies of critically ill PICU patients. Thus, we will test the first pediatric-specific, interprofessional intervention that integrates high protein and individualized exercise. This intervention was developed by a team of experts in the fields of nutrition, early mobility, rehabilitative exercise, muscle ultrasound (US), and functional outcomes. We propose a 2-center, pilot feasibility, randomized controlled trial (PROXIMUS) with the following Specific Aims: 1) To determine the feasibility and safety of a randomized open-label trial comparing high protein combined with individualized exercise vs. standard management during the acute phase of critical illness in children; 2) To determine the impact of high protein and individualized exercise on preservation of muscle mass; and 3) To determine the impact of high protein and individualized exercise on functional status at 1 month and 6 months after randomization. Outcomes: We will assess feasibility with a composite measure that combines predetermined thresholds for screening, enrollment, allocation, and compliance/adherence with significant separation in doses of protein and exercise between the two arms. Safety will be defined as absence of difference in rates of new renal injury and exercise-related adverse events. Preservation of muscle mass will be assessed by percent daily change in US-measured quadriceps femoris muscle thickness (QFMT) during the PICU stay. We will use a validated imaging protocol with high reliability and reproducibility. We will also examine the difference in the normative standard scores (T-scores) between the two arms for the Pediatric Evaluation of Disability Inventory – Computer Adaptive Test (PEDI-CAT) assessment. Other secondary outcomes are Functional Status Scale, PedsQL, and muscle quality by US. We hypothesize that a larger trial will be feasible and safe. Patients randomized to the combined intervention will have lower decline in QFMT and better scores on PEDI-CAT assessment. The PROXIMUS intervention has potential to profoundly change medical care in the PICU and substantially impact public health by improving long-term outcomes for the growing number of pediatric survivors of critical illness

美国儿科重症监护病房 (PICU) 的死亡率正在改善，人们越来越关注幸存者的生活质量，这些幸存者往往存在持续的身体、认知和心理障碍，尤其是机械通气儿童，他们的活动能力较差，营养摄入不足。急性危重疾病期间的早期活动和最佳营养与肌肉质量的保留和机械通气持续时间的缩短有关，但这些干预措施可能有可能减少可预防的 PICU 获得性发病率。这些干预措施的最佳剂量和长期益处尚未在重症监护病房 (PICU) 患者的随机研究中得到证实。因此，我们将测试第一个结合高蛋白和个性化运动的儿科特异性、跨专业干预措施。由营养、早期活动、康复锻炼、肌肉超声（美国）和功能结果领域的专家组成的团队我们提出了一项 2 中心、试点可行性、随机对照试验 (PROXIMUS)，其具体目标如下：1)确定可行性比较儿童危重疾病急性期高蛋白结合个体化运动与标准管理的随机开放试验的安全性；2) 确定高蛋白和个体化运动对保持肌肉质量的影响； ) 为了确定随机分组后 1 个月和 6 个月时高蛋白和个性化运动对功能状态的影响：我们将采用综合措施来评估可行性，该措施将筛查、入组、分配和依从性/依从性的预定阈值与显着性相结合。分离两臂之间蛋白质剂量和运动的安全性将被定义为新肾损伤发生率和运动相关不良事件的发生率不存在差异，肌肉质量的保留将通过超声测量的股四头肌的每日变化百分比来评估。我们将使用经过验证的具有高可靠性和可重复性的成像协议来检查两组之间的标准化标准分数（T 分数）的差异，以进行儿科残疾评估。库存 - 计算机适应性测试 (PEDI-CAT) 评估是美国的功能状态量表、PedsQL 和肌肉质量。我们追求更大规模的试验是可行且安全的，随机接受联合干预的患者将有较低的下降。 QFMT 和 PEDI-CAT 评估得分更高，PROXIMUS 干预措施有可能深刻改变 PICU 的医疗护理，并通过改善越来越多的危重病儿科幸存者的长期结果，对公共健康产生重大影响。