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，导致人们越来越关注幸存者的生活质量，这些幸存者通常具有持续的身体，认知和心理障碍。特别是机械通气的儿童会经历固定和营养摄入不足，导致急性疾病期间肌肉损失。急性危重病期间的早期活动和最佳营养与肌肉质量保护和机械通气持续时间缩短相关。这些干预措施可能有可能减少可预防的PICU获得性发病率。然而，这些干预措施的最佳剂量和长期益处尚未在重症PICU患者的随机研究中显示。因此，我们将测试第一个儿科特定的，跨专业的干预，整合高蛋白质和个性化的运动。这种干预措施是由营养、早期活动、康复锻炼、肌肉超声（US）和功能结果领域的专家团队开发的。我们提出了一个2中心，试点可行性，随机对照试验（PROXIMUS），具体目的如下：1）确定一项随机开放标签试验的可行性和安全性，该试验在儿童危重病急性期比较高蛋白联合个体化运动与标准管理; 2）确定高蛋白和个体化运动对保留肌肉质量的影响;（3）在随机分组后1个月和6个月，确定高蛋白和个体化运动对功能状态的影响。成果：我们将使用一种综合指标评估可行性，该指标将筛选、入组、分配和依从性/依从性的预定阈值与两组之间蛋白质剂量和运动的显著分离相结合。安全性定义为新发肾损伤和运动相关不良事件的发生率无差异。在PICU住院期间，将通过US测量的股四头肌厚度（QFMT）的每日变化百分比评估肌肉质量的保留。我们将使用经过验证的成像方案，具有高可靠性和可重复性。我们还将检查两组儿童残疾评估量表-计算机适应性测试（PEDI-CAT）评估的规范性标准评分（T评分）的差异。其他次要结局是功能状态量表、PedsQL和US肌肉质量。我们假设更大规模的试验是可行和安全的。随机分配到联合干预组的患者QFMT下降幅度较小，PEDI-CAT评估评分较好。PROXIMUS干预有可能深刻改变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局，对公共卫生产生重大影响