Preserving Physical Function in Older Adults with Cancer: Impact of an Optimizing Nutrition Intervention Applied Before and After Surgery

保留患有癌症的老年人的身体功能：手术前后应用优化营养干预的影响

• 批准号: 10643468
• 负责人: Kathryn N Starr
• 金额: --
• 依托单位: DURHAM VA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-07-01 至 2027-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10643468
• 关键词: Activities of Daily Living; Address; Adult; Advanced Malignant Neoplasm; Amino Acids; Anabolism; Anorexia; Biphasic Pattern; Cachexia; Cancer Etiology; Cancer Survivor; Clinical; Compensation; Data; Deterioration; Dietary Intervention; Dimensions; Disease; Elderly; Eligibility Determination; Enrollment; Face; Frail Elderly; Gastrointestinal Surgical Procedures; Genitourinary system; Goals; Health; Healthcare Systems; Impaired wound healing; Inflammation; Intervention; Knowledge; Leucine; Link; Malignant Neoplasms; Malignant neoplasm of gastrointestinal tract; Malnutrition; Metabolic; Mission; Morbidity - disease rate; Multivitamin; Muscle; Muscle function; Muscular Atrophy; Musculoskeletal; Nutrient; Nutritional; Nutritional Support; Operative Surgical Procedures; Ostomy; Outcome; Outcome Measure; Patient-Focused Outcomes; Patients; Perioperative; Personal Satisfaction; Phase; Physical Function; Physiological; Population; Postoperative Complications; Postoperative Period; Pragmatic clinical trial; Protein-Energy Malnutrition; Proteins; Quality of life; Randomized; Randomized, Controlled Trials; Recommendation; Recovery; Regimen; Research; Risk; Risk Factors; Surgical complication; Symptoms; Testing; Urogenital Cancer; Veterans; Vitamin A; Vitamin D; Vomiting; Walking; age-related muscle loss; aged; appetite loss; beta-hydroxyisovaleric acid; cancer cachexia; cancer surgery; cancer therapy; chemotherapy; combat; coping; effective intervention; efficacy evaluation; exercise intensity; exercise intervention; experience; frailty; functional decline; functional improvement; functional restoration; gastrointestinal; high risk; high risk population; improved; lipid metabolism; mortality; neglect; novel; nutrition; nutrition related cancer; older patient; preservation; prevent; protein metabolism; reduce symptoms; research and development; resistance exercise; restoration; secondary outcome; side effect; systemic inflammatory response; targeted treatment; treatment arm; treatment optimization; tumor progression

Cancer is a common cause of [functional decline and morbidity] in older adults, with more than two-thirds of new cases occurring in adults aged 60 years or more. Surgery is the most effective cancer treatment, but it brings many risks that threaten recovery of physical function in older patients. Older adults needing surgical treatment face the threats of age-related loss of muscle [quality, strength and endurance, malnutrition (including cancer-related nutrition impact)], inflammation, and cachexia [caused by cancer and its treatments]. Further, older adults often experience marked deterioration of functional abilities and reduced physical reserve and may never regain their baseline level of physical function. This proposal addresses a gap in knowledge on perioperative interventions to maximize restoration of functional capacity, minimize muscle loss due to catabolic circumstances, and prevent malnutrition for these patients. Because a treatment using several nutrients aimed at multiple mechanisms (targets) is expected to be strongly superior to single nutrient treatment, we will use this approach to target a number of factors involved in cancer cachexia, including anorexia, alterations in fat and protein metabolism, and systemic inflammation, as well as to prevent or correct nutritional deficiencies. We expect this intervention to provide superior recovery of physical function and to improve [physiologic, metabolic] and Veteran-centered outcomes versus a [typical] treatment. Thus, in a pragmatic clinical trial, we will test a multi-targeted nutrition intervention, applied in a biphasic pattern (pre- and post-operatively) in older Veterans newly referred for surgical cancer treatment. In a two-armed 1:1 randomized controlled trial, we will test this nutrition-optimized treatment for senior health (NOSH), a multi-targeted treatment provided in biphasic intervals (8 weeks before and 24 weeks after discharge from surgery), and compare it to a [typical nutrition regimen (Typical )] with regards to (Primary Aim 1) physical function, [(Secondary Aim 2) physiologic and metabolic outcomes], and (Exploratory Aim 3) Veteran-centered outcomes, including quality of life (QoL), cancer-related nutrition impact symptoms, and postoperative outcome measures. Older Veterans approaching surgery for [Stage II-III] gastrointestinal or genitourinary cancer who are at high risk for having their physical abilities markedly decline during treatment will be enrolled and randomized to NOSH or the [Typical regimen], with both groups prescribed low-intensity resistance exercise thrice weekly. The NOSH intervention will include generous high-quality protein (30 g/meal; 1.5 g/kg/d) and other key nutrients linked with muscle preservation, namely b-hydroxy-b- methylbutyrate, a metabolite of the amino acid leucine (HMB; 3 g/d), and vitamin D and a daily multivitamin supplemented to a vitamin D level of 800 IU/d). Aim 1 will evaluate changes in physical function in the NOSH intervention arm relative to the [Typical regimen]. Our working hypothesis is that the NOSH intervention will result in improved physical function (Aim 1) and [physiologic and metabolic outcomes (Aim 2) relative to the Typical regimen.] We also predict improvements in Veteran-centered outcomes (Aim 3). This research addresses an important gap in the evidence for best practice of nutritional care for frail older adults approaching surgical cancer treatment. If the hypotheses of this study are correct, there will be strong evidence for a major change in treatment approaches for a heretofore mostly neglected population of high-risk older adults with cancer. More importantly, this improvement in cancer treatment will lead to stronger, more rapid physical recoveries and better quality of life for this population. The findings will also benefit the VA by decreasing demands on the health care system via reductions in postoperative complications and the hastening of recovery of physical function.

癌症是老年人[功能衰退和发病]的常见原因，超过三分之二的人 新病例发生在 60 岁或以上的成年人中。手术是最有效的癌症治疗方法，但 带来许多威胁老年患者身体功能恢复的风险。需要手术的老年人 治疗面临与年龄相关的肌肉损失[质量、力量和耐力、营养不良 （包括与癌症相关的营养影响）]、炎症和恶病质[由癌症及其相关疾病引起 治疗]。此外，老年人经常会经历功能能力的显着恶化和能力下降。 身体储备，可能永远无法恢复身体机能的基线水平。该提案解决了一个空白 有关围手术期干预的知识，以最大限度地恢复功能能力，最大限度地减少肌肉损失 由于分解代谢情况，并防止这些患者营养不良。因为一次治疗需要使用多种 针对多种机制（目标）的营养素预计将远远优于单一营养素 治疗中，我们将使用这种方法来针对与癌症恶病质有关的许多因素，包括 厌食症、脂肪和蛋白质代谢的改变以及全身炎症，以及预防或纠正 营养缺乏。我们期望这种干预能够使身体功能得到更好的恢复，并 与[典型]治疗相比，改善[生理、代谢]和以退伍军人为中心的结果。因此，在一个 务实的临床试验，我们将测试以双相模式应用的多目标营养干预措施（预 以及手术后）新转诊接受外科癌症治疗的老年退伍军人。 在一项双组 1:1 随机对照试验中，我们将测试这种针对老年人健康的营养优化治疗方法 (NOSH)，一种以双相间隔（治疗前 8 周和治疗后 24 周）提供的多靶点治疗 手术出院），并将其与 [典型营养方案（典型）] 进行比较（主要 目标 1) 身体机能，[（次要目标 2）生理和代谢结果]，以及（探索性目标 3） 以退伍军人为中心的结果，包括生活质量 (QoL)、癌症相关的营养影响症状以及 术后结果测量。年长退伍军人即将接受 [II-III 期] 胃肠道或 泌尿生殖系癌症高危人群，治疗期间体能明显下降 将入组并随机接受 NOSH 或[典型方案]，两组均接受低强度治疗 每周三次抵抗运动。 NOSH 干预措施将包括大量的优质蛋白质（30 克/餐； 1.5克/公斤/天）和其他与肌肉保存相关的关键营养素，即b-羟基-b- 丁酸甲酯、氨基酸亮氨酸的代谢物 (HMB；3 克/天)、维生素 D 和每日多种维生素 补充维生素 D 水平为 800 IU/天）。目标 1 将评估 NOSH 身体功能的变化 相对于[典型方案]的干预组。我们的工作假设是 NOSH 干预将 相对于身体机能（目标 1）和[生理和代谢结果（目标 2）得到改善 典型方案。] 我们还预测以退伍军人为中心的结果会有所改善（目标 3）。 这项研究解决了体弱老年人营养护理最佳实践的证据中的一个重要空白 接受手术癌症治疗的成年人。如果本研究的假设正确，将会有强有力的证据 有证据表明，迄今为止大多被忽视的高危人群的治疗方法发生了重大变化 患有癌症的老年人。更重要的是，癌症治疗的这种进步将带来更强大、更有效的治疗。 该人群的身体恢复速度更快，生活质量更高。研究结果还将有利于退伍军人事务部 通过减少术后并发症和加速治疗来减少对医疗保健系统的需求 身体机能的恢复。