NUTRITIONAL SUPPORT IN PEDIATRIC STEM CELL TRANSPLANTATION: A RANDOMIZED, CON

儿科干细胞移植的营养支持：随机、对照

• 批准号: 7950642
• 负责人: KATHRYN SUETWA LEUNG
• 金额: $ 0.03万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-12-01 至 2009-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7950642
• 关键词: Accounting; Adult; Affect; Age; Allogenic; Autologous; Basal metabolic rate; Biochemical; Body Composition; Body fat; Calories; Cancer Patient; Chemotherapy-Oncologic Procedure; Child; Childhood; Clinical; Clinical Research; Computer Retrieval of Information on Scientific Projects Database; Controlled Clinical Trials; Data; Dietary intake; Disease; Disease remission; Double-Blind Method; Energy Intake; Energy Metabolism; Engraftment; Frequencies; Funding; Grant; Growth; Heart Rate; Hepatotoxicity; High Dose Chemotherapy; Incidence; Indirect Calorimetry; Infection; Institution; Insulin Resistance; Intake; Lead; Liver diseases; Long-Term Survivors; Malignant Neoplasms; Malnutrition; Measurement; Measures; Medical; Metabolic; Methods; Monitor; Mucositis; Nutrient; Nutritional; Nutritional Requirements; Nutritional Support; Nutritional status; Oral; Outcome; Pain; Parenteral Nutrition; Patients; Physical activity; Pilot Projects; Prior Therapy; Proteins; Protocols documentation; Publishing; Randomized; Research; Research Personnel; Resources; Rest; Risk; Solid Neoplasm; Source; Stem cell transplant; Techniques; Time; Transplant Recipients; Transplantation; Treatment Protocols; Tumor Burden; Underweight; United States National Institutes of Health; Visceromegaly; Whole-Body Irradiation; abstracting; adult stem cell transplantation; cancer cell; chemotherapy; cohort; conditioning; gastrointestinal; glycemic control; illness length; improved; mortality; oral mucositis; primary outcome; secondary outcome; sex; standard of care

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. ABSTRACT Children undergoing stem cell transplantation (SCT) often require prolonged courses of parenteral nutrition (PN) to maintain nutritional status during the engraftment period. Although PN has been associated with shorter engraftment time and decreased mortality in these patients, it may also be associated with significant complications, including infections, liver disease, and metabolic disturbances. Some of these complications may be related to providing excessive amounts of parenteral nutrition (overfeeding), although underfeeding is also associated with adverse nutritional and metabolic outcomes. Nutrient and energy needs of children undergoing SCT are not well known, and current practice calls for providing 130-150% of estimated basal energy needs to these patients during the transplant period. We have recently completed a pilot study in a cohort of pediatric allogeneic SCT patients in which parenteral energy intake was titrated to energy expenditure as measured by indirect calorimetry. We noted a substantial decline in resting energy expenditure (REE) during the course of SCT. When engraftment occurred, REE increased to near baseline levels. Since lean body mass is closely correlated with REE, and since SCT patients likely suffer lean body mass depletion with preparative chemotherapy regimens, we hypothesize that changes in body composition affect REE during the post-transplant period, and that standard nutritional support methods may lead to overfeeding. The primary outcome variable is body composition (as measured by dual energy x-ray absorptiometry, DXA), and secondary outcomes include glycemic control, frequency of infectious complications, and select biochemical parameters. Body composition measurements and energy expenditure studies have not been widely studied in pediatric stem cell transplant patients. This study will provide unique and detailed nutritional data on a group of catabolic pediatric patients, and the results will guide their nutritional therapy and may improve clinical outcomes. Children undergoing stem cell transplantation often require parenteral nutrition to provide adequate calories and protein due to severe mucositis and other gastrointestinal complications of the preparative regimen (1). Accurate provision of energy may reduce complications related to overfeeding (2) or underfeeding (3). We hypothesize that changes in body composition during SCT affect REE, and that the standard approach to nutritional management of these patients may lead to overfeeding. Specifically, we hypothesize that: 1. Children receiving nutritional support titrated to measured energy expenditure will have more optimal body composition (comparable lean body mass, lower percent body fat) than those provided nutritional support in the standard fashion. 2. Children receiving nutritional support titrated to measured energy expenditure will have improved glycemic control and decreased insulin resistance than those provided nutritional support in the standard fashion. 3. Compared with published norms, children undergoing SCT have altered rates of resting energy expenditure (REE). 4. Anticipated changes in REE are correlated with changes in lean body mass during SCT. 5. Children receiving nutritional support titrated to measured energy expenditure will resume oral intake sooner than those provided nutritional support in the standard fashion. SPECIFIC AIMS To conduct a randomized, double-blinded controlled clinical trial among pediatric SCT patients comparing two methods of nutritional support: 1) standard of care (the provision of 130-150% of estimated basal energy needs via parenteral nutrition), and 2) an experimental protocol in which energy intake is titrated to match resting energy expenditure as measured by indirect calorimetry. Primary Aims: 1. To compare the effects of standard vs. titrated nutritional support in pediatric SCT patients on percent body fat, as measured by DXA. 2. To compare the effects of standard vs. titrated nutritional support in pediatric SCT patients on glycemic control and insulin resistance. 3. To measure serial changes in REE over the course of SCT with indirect calorimetry. 4. To correlate anticipated changes in REE with changes in body composition. Secondary Aim: 1. To measure resumption of oral dietary intake after SCT. Malnutrition and Cancer: Cancer patients have a high incidence of malnutrition (4, 5). Children have increased energy needs for growth and are thus at greater risk of malnutrition than adults. Children undergoing stem cell transplantation are among those with highest nutritional risk due to their underlying disease and the intensive medical therapy prior to and following transplant (1). Significant declines in lean body mass and energy intake have been found in children undergoing chemotherapy (6, 7). High dose chemotherapy and total body irradiation as conditioning for SCT often produce painful oral mucositis that can reduce nutritional intake for days to weeks. Parenteral nutrition (PN) is routinely utilized during SCT since it has been associated with faster engraftment and improved survival (8, 9). Studies supporting the efficacy of PN, however, were performed in a single center nearly 20 years ago. Moreover, complications of PN include infections, hepatotoxicity, suppression of oral intake, and metabolic abnormalities. Provision of appropriate nutritional requirements while minimizing potential risks has been difficult without a clearer understanding of energy and nutrient needs of children undergoing SCT. Resting Energy Expenditure (REE) in Cancer Patients The energy needs of rapidly dividing cancer cells may increase basal metabolic demands of the host from 20 to 90% over predicted needs. Since basal energy needs account for a substantial portion of total energy needs, any increment in basal energy requirements can result in energy imbalance. Knox et al. (10) studied 200 adult cancer patients using the technique of indirect calorimetry, a non-invasive bedside measure of REE, the clinical estimate of basal metabolic rate (11). One-third of their patients were hypometabolic (REE was < 90% of predicted levels), one fourth were hypermetabolic (REE > 110% predicted), and the remaining 40% had normal REE (between 90 and 110% predicted). Older subjects, those with longer duration of disease, and underweight patients tended to have higher REE measurements. A small study of 6 autologous and 5 allogeneic adult SCT patients used indirect calorimetry prior to and during transplant. Allogeneic SCT patients had on average an 8% reduction in REE while autologous patients had an 11% increase, compared to predicted levels. This study suggests that the nutritional requirements of adults undergoing autologous or allogeneic SCT vary due to differences in treatment (12). Larger studies are needed to determine changes in requirements within each transplant group. Fewer studies of energy metabolism have been performed in children with cancer. Stallings et al. measured REE in 9 patients with ALL and found that patients with a higher tumor burden (elevated WBC count, organomegaly) had an increased REE (13). A study of 26 patients with ALL or solid tumors in remission showed no evidence of an increased resting energy expenditure, when compared to age- and sex-matched healthy controls (14). Using a combination of indirect calorimetry and ambulatory heart rate monitoring to measure REE and total energy expenditure (TEE) in 34 long-term survivors of ALL, Warner et al. concluded that ALL patients have lower levels of TEE largely related to reduced physical activity (15).

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 抽象的 接受干细胞移植（SCT）的儿童通常需要长时间的肠外营养（PN）以维持植入期间的营养状态。 尽管 PN 与这些患者的植入时间缩短和死亡率降低有关，但它也可能与严重的并发症有关，包括感染、肝病和代谢紊乱。其中一些并发症可能与提供过量的肠外营养（过度喂养）有关，尽管喂养不足也与不良的营养和代谢结果有关。接受 SCT 的儿童的营养和能量需求尚不清楚，目前的做法要求在移植期间为这些患者提供估计基础能量需求的 130-150%。我们最近在一组儿科同种异体 SCT 患者中完成了一项试点研究，其中肠外能量摄入量根据间接量热法测量的能量消耗进行滴定。我们注意到 SCT 过程中静息能量消耗 (REE) 大幅下降。当植入发生时，稀土元素增加到接近基线水平。由于去脂体重与 REE 密切相关，并且由于 SCT 患者可能会因预备化疗方案而遭受去脂体重消耗，因此我们假设身体成分的变化会在移植后影响 REE，而标准的营养支持方法可能会导致过度喂食。主要结果变量是身体成分（通过双能 X 射线吸收测定法 (DXA) 测量），次要结果包括血糖控制、感染并发症的频率和选择的生化参数。儿童干细胞移植患者的身体成分测量和能量消耗研究尚未得到广泛研究。这项研究将为一组分解代谢儿科患者提供独特而详细的营养数据，结果将指导他们的营养治疗并可能改善临床结果。 由于严重的粘膜炎和准备方案的其他胃肠道并发症，接受干细胞移植的儿童通常需要肠外营养以提供足够的热量和蛋白质(1)。准确的能量供应可以减少与过度喂养 (2) 或喂养不足 (3) 相关的并发症。我们假设 SCT 期间身体成分的变化会影响 REE，并且这些患者的标准营养管理方法可能会导致过度喂养。具体来说，我们假设： 1. 与以标准方式提供营养支持的儿童相比，接受根据测量的能量消耗进行滴定的营养支持的儿童将具有更佳的身体成分（可比较的去脂体重、较低的体脂百分比）。 2. 与以标准方式提供营养支持的儿童相比，接受根据测量的能量消耗进行滴定的营养支持的儿童将改善血糖控制并降低胰岛素抵抗。 3. 与公布的标准相比，接受 SCT 的儿童的静息能量消耗 (REE) 发生了变化。 4. REE 的预期变化与 SCT 期间去脂体重的变化相关。 5. 接受根据测量的能量消耗进行滴定的营养支持的儿童将比以标准方式提供营养支持的儿童更快地恢复经口摄入。 具体目标 在儿科 SCT 患者中进行一项随机、双盲对照临床试验，比较两种营养支持方法：1) 标准护理（通过肠外营养提供估计基础能量需求的 130-150%），2) 实验性营养支持协议中，通过间接量热法测量能量摄入量，以匹配静息能量消耗。 主要目标： 1. 比较标准营养支持与滴定营养支持对儿科 SCT 患者体内脂肪百分比（通过 DXA 测量）的影响。 2. 比较儿科 SCT 患者标准营养支持与滴定营养支持对血糖控制和胰岛素抵抗的影响。 3. 使用间接量热法测量 SCT 过程中 REE 的系列变化。 4. 将 REE 的预期变化与身体成分的变化联系起来。 次要目标： 1. 测量 SCT 后口服饮食摄入的恢复情况。 营养不良与癌症：癌症患者营养不良的发生率很高 (4, 5)。儿童生长所需的能量增加，因此比成人面临更大的营养不良风险。 由于其基础疾病以及移植前后的强化药物治疗，接受干细胞移植的儿童属于营养风险最高的人群 (1)。接受化疗的儿童的去脂体重和能量摄入量显着下降 (6, 7)。 高剂量化疗和全身放疗作为 SCT 的条件治疗通常会产生疼痛的口腔粘膜炎，从而导致数天至数周的营养摄入减少。 SCT 期间常规使用肠外营养 (PN)，因为它与更快的植入和提高存活率相关 (8, 9)。然而，支持 PN 功效的研究是在近 20 年前在一个中心进行的。此外，PN 的并发症包括感染、肝毒性、口服摄入抑制和代谢异常。如果不能更清楚地了解接受 SCT 的儿童的能量和营养需求，就很难在提供适当的营养需求的同时将潜在风险降至最低。 癌症患者的静息能量消耗 (REE) 快速分裂的癌细胞的能量需求可能会使宿主的基础代谢需求比预测需求增加 20% 至 90%。由于基础能量需求占总能量需求的很大一部分，基础能量需求的任何增加都可能导致能量失衡。诺克斯等人。 (10) 使用间接量热法技术研究了 200 名成年癌症患者，这是一种非侵入性床边 REE 测量方法，用于基础代谢率的临床估计 (11)。三分之一的患者代谢低下（REE < 预测水平的 90%），四分之一的患者代谢亢进（REE > 预测水平的 110%），其余 40% 的 REE 正常（预测水平在 90% 到 110% 之间）。年龄较大的受试者、病程较长的受试者和体重过轻的患者往往具有较高的 REE 测量值。一项针对 6 名自体和 5 名同种异体成人 SCT 患者的小型研究在移植前和移植期间使用了间接量热法。 与预测水平相比，同种异体 SCT 患者的 REE 平均减少 8%，而自体 SCT 患者的 REE 增加 11%。这项研究表明，接受自体或同种异体 SCT 的成人的营养需求因治疗的差异而异 (12)。需要更大规模的研究来确定每个移植组内需求的变化。 对患有癌症的儿童进行的能量代谢研究较少。 斯托林斯等人。测量了 9 名 ALL 患者的 REE，发现肿瘤负荷较高（白细胞计数升高、器官肿大）的患者的 REE 增加 (13)。一项针对 26 名缓解期 ALL 或实体瘤患者的研究显示，与年龄和性别匹配的健康对照相比，没有证据表明静息能量消耗增加 (14)。 Warner 等人结合间接量热法和动态心率监测来测量 34 名 ALL 长期幸存者的 REE 和总能量消耗 (TEE)。得出的结论是，ALL 患者 TEE 水平较低，很大程度上与体力活动减少有关 (15)。