Patient-Oriented Research in Arginine Deficiency Syndromes

以患者为导向的精氨酸缺乏综合征研究

• 批准号: 10468085
• 负责人: Claudia R Morris
• 金额: $ 17.78万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-24 至 2023-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10468085
• 关键词: Absence of pain sensation; Academy; Accident and Emergency department; Acute; Acute Pain; Address; American; Amino Acids; Area; Arginine; Award; Blood; Child; Childhood; Clinical; Clinical Nutrition; Clinical Research; Clinical Sciences; Clinical Trials; Committee Members; Critical Care; Data; Death Rate; Development; Discipline; Drug Kinetics; Ear Acupuncture; Educational Curriculum; Educational workshop; Emergency Medicine; Emergency department visit; Enrollment; Environment; Event; Extramural Activities; Faculty; Fellowship; Follow-Up Studies; Fostering; Funding; Future; Goals; Grant; Hematology; Hospitalization; Hospitals; Hour; Hydration status; Infrastructure; Inpatients; Institutes; Integrative Medicine; International; Intervention; Lead; Leadership; Length of Stay; Master of Science; Medical Students; Medicine; Mentors; Mentorship; Mid-Career Clinical Scientist Award (K24); Narcotics; National Center for Complementary and Integrative Health; National Heart, Lung, and Blood Institute; Nephrology; Nitric Oxide; Nutritional; Nutritional Science; Nutritional Study; Pain; Patient Care; Patients; Pediatric Research; Pediatrics; Phase; Placebos; Postdoctoral Fellow; Product Approvals; Production; Program Development; Publications; Pulmonology; Randomized; Research; Research Activity; Research Personnel; Research Support; Resolution; Resources; Role; Safety; Schools; Scientist; Sickle Cell; Sickle Cell Anemia; Supplementation; Syndrome; TNFSF15 gene; Time; Training; Translational Research; Universities; Vasodilator Agents; acute care; arginine treatment; base; career; career development; certificate program; clinical practice; clinically relevant; dietary supplements; double-blind placebo controlled trial; evidence base; graduate student; improved; interest; leadership development; metabolome; mortality; neglect; new therapeutic target; next generation; novel therapeutics; opioid use; pain score; patient oriented research; pediatric department; pediatric emergency; phase III trial; product development; programs; randomized placebo-controlled clinical trial; recruit; skills; success; trend; undergraduate student; ward; willingness; women faculty

This K24 application entitled “Patient-Oriented Research (POR) in Arginine (Arg) Deficiency Syndromes” seeks 5 years of support for protected time to expand the principle investigator's (PI) mentoring activities, promote her career development & provide momentum to advance the applicant's research evaluating Arg therapy in sickle cell disease (SCD) and beyond. Arg is a nutritional supplement & obligate substrate for the production of nitric oxide, a potent vasodilator that becomes depleted during episodes of SCD-related pain and contributes to vaso- occlusion. The PI has completed a single-center randomized, double-blinded, placebo-controlled trial (RCT) of Arg therapy in 54 children with pain requiring hospitalization. She observed a reduction in opioid usage by over 54%, lower pain scores, and a clinically relevant trend towards decreased length of hospital stay in children who received 5 days of Arg therapy compared to placebo. She has an active research program that includes a FDA- sponsored Phase 2 RCT and a NHLBI-supported pharmacokinetics study of Arg therapy to treat SCD-related pain that is currently enrolling patients. The PI proposes to extend these studies to a definitive multi-center Phase 3 trial. Pain in SCD is the leading cause of hospitalizations, emergency room (ED) visits, missed school & is associated with an increased mortality rate. There are no current therapies to treat the underlying mechanisms of pain, with interventions limited to hydration and analgesia. The PI hypothesizes that Arg is a safe & inexpensive nutritional supplement with narcotic-sparing effects in pediatric SCD patients and pain. Her current and future study aims will determine the safety & efficacy of arginine therapy to reduce time to pain crisis resolution and total parenteral opioid use (mg/kg) in children with SCD & pain. This proposal will provide essential data for product development and will ultimately help gain FDA product approval for SCD if benefits of Arg therapy are confirmed in follow-up studies. Acute care of patients with SCD & pain in the ED is a neglected area of research. The results of this proposal may ultimately lead to a change in clinical practice for patients with SCD in both the ED & inpatient hospital wards. ED-based studies and novel therapies that target mechanisms of pain are needed in SCD. In addition, the PI is highly committed to performing POR focused on nutrition science & in growing her mentorship reach to include a diverse group of undergraduate's, graduate & medical students, post- doctoral fellows & junior faculty in clinical nutrition research, having mentored scholarly activity for over 35 mentees already during the course of her career. During the 5-year grant, the candidate will also participate in a number of mid-career leadership & mentorship courses, choosing curriculums that will help advance the candidate as an educational leader & mentor within academic medicine. The environment at Emory University is ideal to foster these goals, and will enhance the career development of the applicant as a mentor champion in integrative medicine in partnership with the Atlanta Clinical and Translational Science Institute, thereby enabling her to train mentees in the field and increase the pool of evidence-based integrative clinical scientists.

本 K24 申请题为“精氨酸 (Arg) 缺乏综合症的患者导向研究 (POR)”，旨在寻求 5 年受保护时间支持，以扩大首席研究员 (PI) 的指导活动，促进她的发展 职业发展并为推进申请人评估镰状精氨酸疗法的研究提供动力 精氨酸是一种营养补充剂和产生硝酸的必需底物。 氧化物，一种有效的血管扩张剂，在 SCD 相关疼痛发作期间会耗尽，并导致血管 PI 已完成一项单中心随机、双盲、安慰剂对照试验 (RCT)。 她观察到 54 名因疼痛需要住院治疗的儿童使用 Arg 疗法后，阿片类药物的使用量减少了超过 10%。 54%，疼痛评分较低，并且临床相关趋势是儿童住院时间缩短 与安慰剂相比，她接受了 5 天的 Arg 治疗，她有一个积极的研究计划，其中包括 FDA-。 赞助的 2 期 RCT 和 NHLBI 支持的 Arg 疗法治疗 SCD 相关的药代动力学研究 目前正在招募患者，PI 建议将这些研究扩展到确定的多中心阶段。 3 试验中，SCD 疼痛是导致住院、急诊 (ED) 就诊、缺课的主要原因。 与死亡率增加相关，目前没有治疗方法可以治疗潜在的机制。 疼痛，干预措施仅限于水合和镇痛。 廉价的营养补充剂，对儿科 SCD 患者具有节省麻醉作用和缓解疼痛的作用。 未来的研究目标将确定精氨酸疗法的安全性和有效性，以缩短疼痛危机的时间 患有 SCD 和疼痛的儿童的分辨率和父母阿片类药物的总使用量（毫克/千克）该提案将提供必要的信息。 产品开发的数据，如果 Arg 的益处，最终将有助于获得 FDA 对 SCD 产品的批准 后续研究证实了 SCD 和急诊室疼痛患者的紧急护理是一个被忽视的领域。 该提案的结果可能最终会导致 SCD 患者的临床实践发生变化。 在急诊科和住院病房进行基于急诊科的研究和针对疼痛机制的新疗法。 此外，PI 高度致力于执行专注于营养科学和领域的 POR。 扩大她的指导范围，涵盖本科生、研究生和医学生、研究生等不同群体 临床营养研究领域的博士研究员和初级教师，指导了超过 35 名学术活动 在为期 5 年的资助期间，候选人还将参加一个项目。 职业中期领导力和指导课程的数量，选择有助于推进职业发展的课程 埃默里大学学术医学领域的教育领导者和导师候选人。 是实现这些目标的理想选择，并将促进申请人作为导师冠军的职业发展 与亚特兰大临床和转化科学研究所合作，获得综合医学博士学位，从而 使她能够在该领域培训学员并增加循证综合临床科学家的人才库。