VitaminA and Sickle Cell Disease:Improving Suboptimal Status with Supplementation

维生素 A 和镰状细胞病：通过补充改善亚健康状态

• 批准号: 8581238
• 负责人: Kelly Ann Dougherty
• 金额: $ 15.26万
• 依托单位: CHILDREN'S HOSP OF PHILADELPHIA
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-08-15 至 2017-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8581238
• 关键词: Address; Adolescent; Adult; Adverse effects; Adverse event; Affect; African American; Age; Albumins; All-Trans-Retinol; Anemia; Attenuated; Biometry; Body Weight; Child; Childhood; Chronic; Chronic Disease; Clinical; Clinical Investigator; Clinical Nutrition; Clinical Research; Clinical Trials; Clinical Trials Design; Country; Dark Adaptation; Data; Deuterium; Development; Dietary Intervention; Dilution Techniques; Doctor of Medicine; Doctor of Philosophy; Dose; Environment; Event; Faculty; Feces; Fellowship; Foundations; Funding; Future; Gender; Gold; Growth; Growth and Development function; Health; Hospitalization; Hour; Human; Immunity; Incidence; Individual; Infection; Inflammation; Institute of Medicine (U.S.); Intake; Intervention; Intervention Studies; Knowledge; Label; Life; Liver; Liver Function Tests; Measures; Mentors; Metabolism; Methodology; Methods; Morbidity - disease rate; Muscle function; Nutrient; Operative Surgical Procedures; Ophthalmology; Oral; Outcome; Pain; Patients; Pediatric Hospitals; Pediatric Research; Pediatrics; Pennsylvania; Philadelphia; Physical activity; Physiological; Pilot Projects; Placebos; Population; Prevention; Quality of life; Recommended Daily Allowances; Relative (related person); Reproduction; Research; Research Design; Research Ethics; Research Personnel; Research Project Grants; Resistance to infection; Retinol Binding Proteins; Risk; Safety; Serum; Sickle Cell Anemia; Site; Supplementation; Symptoms; Techniques; Testing; Time; Tissues; Training; Training Programs; Translational Research; United States National Institutes of Health; Universities; Urine; Virginia; Vision; Vitamin A; Vitamin A Deficiency; Vitamins; Work; Xerophthalmia; base; career development; clinical care; comparison group; design; epidemiology study; experience; eye dryness; immune function; improved; innovation; liver biopsy; liver function; medical schools; meetings; mortality; nutrition; patient oriented; professor; research study; response; screening; skills; stable isotope; standard measure; stressor

DESCRIPTION (provided by applicant): Kelly Dougherty, Ph.D., is an Assistant Professor of Pediatrics at University of Pennsylvania (UPenn) Perelman School of Medicine and The Children's Hospital of Philadelphia (CHOP). Dr. Dougherty proposes a comprehensive, interdisciplinary training program that will provide her with the skills and experience necessary to develop into an independent academic patient-oriented investigator in pediatric research, focusing on clinical trials addressing nutrition- and physical activity-related issues affecting children with sickle cell disease (SCD). Her career development will be guided by an accomplished team of investigators in nutrition, growth, chronic disease, stable isotope assessment, ophthalmology, epidemiology / study design and biostatistics. Her primary mentor, Virginia Stallings, M.D. has conducted pediatric clinical nutrition and chronic disease research for the last 27 years and as Director of the Office of Faculty Development at CHOP, has an superb reputation for supporting the development of junior faculty into independent, NIH-funded, clinical investigators. The proposed mentored experience will take place in one of the most outstanding nutrition and SCD clinical research environments in the country. Dr. Dougherty's training will include advanced formal coursework in research design, biostatistics, research ethics and stable isotopes. This training is crucial to build upon the foundations of nutrition and SCD research knowledge that she obtained during her postdoctoral fellowship and UPenn Masters in Translational Research (MTR) thesis work and to prepare her for future R01 submissions to conduct nutrition intervention studies in children with SCD. The proposed research project will focus on suboptimal vitamin A (vit A) status which is prevalent in children with type SS sickle cell disease (SCD-SS) and associated with hospitalizations and poor growth and hematological status. The preliminary data in children with SCD-SS show that vit A supplementation at the dose recommended for healthy children failed to improve vit A status, resulting in no change in hospitalizations, growth or dark adaptation. This indicates an increased vit A requirement most likely due to chronic inflammation, low vit A intake and possible stool or urine loss. The dose of vit A needed to optimize vit A status in subjects with SCD-SS is unknown. The proposed research study will establish the safety and efficacy of vit A supplementation doses (3000 and 5000 IU/d) compared to placebo over 3 months in 66 children with SCD-SS, age 9-to 18-yrs and test the impact of vit A supplementation on the key functional and clinical outcomes. The key safety measures are concurrently elevated serum retinol (age specific) and liver function tests (3x age specific). Efficacy is evaluated by repletion of liver vt A stores using state of the art stable isotope methods. In SCD-SS, total body vit A pool size and liver vit A concentration are assessed before and after the 3 month intervention using the deuterated-retinol-dilution technique. Baseline vit A status will be assessed in similar healthy subjects as a comparison group. Vit A therapy has great promise to safely and economically improve complications and quality of life for patients with SCD. Well-designed trials are urgently needed to determine the clinical impact of vit A supplementation and this study is the next step.

描述（由申请人提供）：Kelly Dougherty博士，是宾夕法尼亚大学（Upenn）Perelman医学院和费城儿童医院（CHOP）的儿科助理教授。 Dougherty博士提出了一项全面的跨学科培训计划，该计划将为她提供所需的技能和经验，以发展为儿科研究的独立的以患者为导向的研究人员，重点是针对影响营养和体育活动相关的临床试验，该试验影响营养和体育活动，影响儿童患有镰状细胞病（SCD）的儿童。她的职业发展将由一支成熟的营养，生长，慢性疾病，稳定同位素评估，眼科，流行病学 /研究设计和生物统计学组成的研究人员指导。她的主要导师弗吉尼亚摊位，医学博士在过去的27年中一直在进行小儿临床营养和慢性病研究，作为CHOP教师发展办公室主任，在支持将初级教师发展成独立，NIH资助的临床研究人员方面享有很高的声誉。拟议的指导经验将在该国最杰出的营养和SCD临床研究环境之一中进行。 Dougherty博士的培训将包括研究设计，生物统计学，研究伦理和稳定同位素的高级正式课程。这项培训对于建立营养基础至关重要 SCD的研究知识在博士后奖学金和UPENN转化研究（MTR）论文工作中获得的知识，并为她准备将来的R01提交准备，以对SCD儿童进行营养干预研究。拟议的研究项目将集中于次优的维生素A（VIT A）状态，该状态在患有SS型镰状细胞疾病（SCD-SS）的儿童中很普遍，并且与住院以及较差的生长和血液学状态有关。 SCD-SS儿童的初步数据表明，建议为健康儿童建议补充剂量，无法改善VIT状态，导致住院，生长或黑暗适应性变化。这表明VIT增加的需求最有可能是由于慢性炎症，VIT摄入量低以及可能的粪便或尿液损失。 VIT A的剂量A在患有SCD-SS的受试者中优化VIT A的状态所需的剂量尚不清楚。拟议的研究将建立补充剂量（3000和5000 IU/d）的安全性和功效，而安慰剂在66名SCD-SS，9至18岁的儿童中与安慰剂相比，并测试了VIT对关键功能和临床结果的影响。关键的安全措施同时升高血清视网膜（特定年龄）和肝功能测试（特定于3倍年龄）。通过使用最先进的同位素方法的状态对肝脏VT A商店的补充来评估功效。在SCD-SS中，使用氘化 - 续航醇稀释技术在三个月干预之前和之后评估了总体vit池大小和肝脏vit。基线VIT将在类似的健康受试者中评估状态作为比较组。 VIT疗法有很大的希望，可以安全，经济改善SCD患者的并发症和生活质量。迫切需要精心设计的试验来确定VIT补充的临床影响，这项研究是下一步。