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).

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 抽象的 接受干细胞移植（SCT）的儿童通常需要长时间的肠胃外营养（PN），以在植入期间保持营养状况。 尽管PN与这些患者的植入时间较短和死亡率降低有关，但它也可能与重大并发症有关，包括感染，肝病和代谢障碍。这些并发症中的一些可能与提供过量的肠胃外营养（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，目前的实践要求在移植期为这些患者提供130-150％的基础能量需求。我们最近在一系列小儿同种异体SCT患者中完成了一项试点研究，其中肠胃外能量摄入被滴定到通过间接热量法测量的能量消耗中。我们注意到SCT过程中的静息能量支出（REE）大幅下降。当植入发生时，REE增加到接近基线水平。由于瘦体重与REE密切相关，并且由于SCT患者可能会因制备化疗方案而遭受瘦体重耗尽，因此我们假设在移植后期，身体成分的变化会影响REE，并且标准的营养支持方法可能导致过度喂养。主要结果变量是身体成分（通过双能X射线吸收仪，DXA测量），次级结果包括血糖控制，传染性并发​​症的频率和选择的生化参数。身体成分测量和能量消耗研究尚未在小儿干细胞移植患者中得到广泛研究。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，结果将指导其营养疗法，并可能改善临床结果。 接受干细胞移植的儿童通常需要肠胃外营养，以提供足够的卡路里和蛋白质，这是由于严重的粘膜炎和其他制备方案的胃肠道并发症（1）。精确提供能量可能会减少与过度喂养（2）或喂养不足有关的并发症（3）。我们假设SCT期间身体成分的变化会影响REE，并且这些患者营养管理的标准方法可能导致过度喂养。具体来说，我们假设： 1。接受滴定到测量能量消耗的营养支持的儿童比以标准方式提供营养支持的孩子更具最佳的身体成分（可比的瘦体重，较低的体内脂肪）。 2。接受滴定到测量能量消耗的营养支持的儿童将改善血糖控制和胰岛素抵抗的降低，而胰岛素抵抗比标准方式提供了营养支持。 3。与已发表的规范相比，接受SCT的儿童的静息能量支出发生率（REE）。 4。REE的预期变化与SCT期间瘦体重的变化相关。 5。接受滴定到测量能量消耗的营养支持的儿童比以标准方式提供营养支持的孩子更快地恢复口服摄入量。 具体目标 比较两种营养支持方法的小儿SCT患者的随机，双盲对照临床试验：1）护理标准（提供130-150％的通过肠胃外营养估计的基础能量需求的130-150％），以及2）一种实验方案，其中能量进气滴定以滴定以匹配静息能量，以匹配按下calorect calorimetect calorimerimerimetrysections sume sume sumepertion。 主要目的： 1。用DXA测量，比较小儿SCT患者对体内脂肪百分比的影响。 2。为了比较标准的滴定营养支持对小儿SCT患者对血糖控制和胰岛素抵抗的影响。 3。通过间接量热法测量SCT过程中REE的串行变化。 4。将REE的预期变化与身体成分的变化相关联。 次要目的：1。测量SCT后口服饮食摄入的恢复。 营养不良和癌症：癌症患者的营养不良发生率很高（4，5）。儿童的生长能量需求增加，因此比成年人更有营养不良的风险。 接受干细胞移植的儿童是由于其潜在疾病和移植前后的强化医疗疗法而受到营养风险最高的患者之一（1）。在接受化学疗法的儿童中发现了瘦体重和能量摄入量的显着下降（6，7）。 高剂量的化疗和全身辐照作为SCT的调节通常会产生疼痛的口腔粘膜炎，可以减少几天到几周的营养摄入量。 肠胃外营养（PN）在SCT期间通常使用，因为它与更快的植入和提高的生存率相关（8、9）。然而，几乎在20年前，在一个中心进行了支持PN功效的研究。此外，PN的并发症包括感染，肝毒性，口服摄入的抑制和代谢异常。在不清楚地了解接受SCT的儿童的能量和营养需求的情况下，很难提供适当的营养需求，同时最大程度地降低潜在风险。 癌症患者的静止能量消耗（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从20％增加到90％，而不是预测的需求。由于基础能量需求占总能源需求的很大一部分，因此基础能量需求的任何增加都可能导致能量失衡。诺克斯等。 （10）使用间接量热法的技术研究了200名成年癌症患者，REE的无创床边测量是基础代谢率的临床估计值（11）。他们的患者中有三分之一是转谢代谢（REE <占预测水平的90％），四分之一是多代谢（REE> 110％的预测），其余40％的REE为正常（预测90％至110％）。较老的受试者，疾病持续时间较长的患者和体重不足的患者往往具有更高的REE测量值。一项针对6例自体和5例同种异体SCT患者的小型研究使用了移植前后的间接量热法。 与预测水平相比，同种异体SCT患者的REE平均降低了8％，而自体患者增加了11％。这项研究表明，由于治疗的差异，经历自体或同种异体SCT的成年人的营养需求有所不同（12）。需要较大的研究来确定每个移植组内需求的变化。 在癌症儿童中，对能量代谢的研究较少。 Stallings等。在9例患者中测量了REE，发现肿瘤负担更高（WBC计数升高，有机肥大）的患者增加了REE（13）。与年龄和性别匹配的健康对照相比，对26名患有所有或实体瘤的患者的研究没有显示出静息能量消耗增加的证据（14）。 Warner等人使用间接量热法和卧床心率监测的组合来测量34个长期幸存者中的REE和总能量消耗（TEE），Warner等人。得出结论，所有患者的TEE水平较低与体育锻炼的降低有关（15）。