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: 10737718
• 负责人: Claudia R Morris
• 金额: $ 14.46万
• 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 2028-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10737718
• 关键词: Absence of pain sensation; Academy; Accident and Emergency department; Acute; Acute Pain; Address; American; Amino Acids; Analgesics; Applied Research; Arginine; Award; Blood; Cardiopulmonary; Child; Childhood; Clinical; Clinical Nutrition; Clinical Research; Clinical Sciences; Clinical Trials; Committee Members; Data; Death Rate; Development; Development Plans; Dose; Education; Educational Curriculum; Educational workshop; Emergency Care; Emergency Medicine; Emergency department visit; Environment; Event; Extramural Activities; Faculty; Fellowship; Fostering; Funding; Goals; Grant; Hospitalization; Hydration status; Infrastructure; Institution; Integrative Medicine; International; Intervention; Investments; Leadership; Length of Stay; Manuscripts; Master of Science; Medical Students; Medicine; Mentors; Mentorship; Mid-Career Clinical Scientist Award (K24); Mitochondria; National Center for Complementary and Integrative Health; National Heart, Lung, and Blood Institute; Nigeria; Nitric Oxide; Nutritional; Nutritional Science; Nutritional Study; Nutritional Support; Opioid; Oxidative Stress; Pain; Pain management; Patient Admission; Patients; Pediatrics; Peer Review; Phase; Physicians; Placebos; Postdoctoral Fellow; Product Approvals; Production; Productivity; Publications; Publishing; Randomized; Replacement Therapy; Research; Research Activity; Research Personnel; Resolution; Resource-limited setting; Role; Safety; Schools; Scientist; Sickle Cell; Sickle Cell Anemia; Supplementation; Syndrome; TNFSF15 gene; Therapy trial; Time; Training; Translational Research; Universities; Vasodilator Agents; Visit; Woman; arginine treatment; career; career development; clinical practice; dietary supplements; double-blind placebo controlled trial; efficacy evaluation; evidence base; graduate student; improved; interest; matriculation; metabolome; mortality; next generation; novel therapeutics; opioid sparing; opioid use; pain score; patient oriented research; pediatric emergency; phase III trial; product development; randomized placebo-controlled clinical trial; skills; success; undergraduate student; willingness

This K24 renewal application entitled “Patient-Oriented Research (POR) in Arginine (ARG) Deficiency Syndromes” seeks 5 years of additional support for protected time to maintain the principle investigator’s (PI) mentoring activities, promote her career development & provide ongoing 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. The PI & her mentees have completed several randomized, double-blinded, placebo- controlled trials (RCT) of ARG therapy in children with SCD & pain requiring hospitalization in both the US & Nigeria. These studies combined found that ARG replacement therapy (ART) has opioid-sparing effects, improved pain scores & cardiopulmonary function, decreased pain medication use & time-to-crisis-resolution and was associated with a shorter hospital stay compared to placebo. The PI and colleagues also observed a dose-dependent impact of ART that improved mitochondrial function & decreased oxidative stress in children with SCD-pain. With recent NHLBI funding for a multicenter Phase 3 RCT utilizing the Pediatric Emergency Care Applied Research Network (PECARN), the PI plans to perform the definitive study - Sickle Cell Disease Treatment with Arginine Therapy (STArT) to determine the efficacy & safety of ART. Pain in SCD is the leading cause of emergency room (ED) visits & hospitalizations, associated with an increased mortality rate. There are no current therapies to treat the underlying mechanisms of acute pain, with interventions limited to hydration & analgesia. The PI hypothesizes that ARG is a safe & inexpensive nutritional supplement with opioid-sparing effects in children with SCD & pain, with potential value in low-resource environments. The STArT trial will provide essential data for product development & will ultimately help gain FDA product approval for SCD if benefits of ART are confirmed. The results of this proposal may ultimately lead to a change in clinical practice for patients with SCD and targets an NCCIH strategic priority of non-pharmacologic management of pain. The PI is highly committed to performing POR focused on nutrition science & in growing her mentorship reach to include a diverse group of undergraduates, medical students, post-doctoral fellows & junior faculty, particularly women & underrepresented physicians in clinical nutrition research, having mentored over 40 trainees throughout her career. During the 5-year grant renewal, the candidate will also participate in a number of leadership & mentorship courses, choosing curricula 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 Georgia Clinical & Translational Science Alliance, enabling her to train mentees in the field & increase the pool of evidence-based integrative clinical scientists.

这项K24更新申请题为“精氨酸（ARG）缺乏症的患者导向研究（POR）” Syntax”寻求5年的额外支持，以保护主要研究者（PI）的时间 辅导活动，促进她的职业发展，并提供持续的动力，以提高申请人的 评估ARG治疗镰状细胞病（SCD）及其他疾病的研究。ARG是一种营养补充剂& 一氧化氮生成的专性底物，一氧化氮是一种有效的血管扩张剂，在发作期间耗尽 与SCD相关的疼痛PI和她的学员已经完成了几个随机，双盲，安慰剂- ARG治疗需要住院治疗的SCD和疼痛儿童的对照试验（RCT）， 尼日利亚。这些研究结合起来发现，ARG替代疗法（ART）具有阿片类药物节省作用， 改善疼痛评分和心肺功能，减少止痛药使用和危机解决时间 并且与安慰剂相比住院时间更短。PI及其同事还观察到 ART改善儿童线粒体功能并降低氧化应激的剂量依赖性影响 SCD疼痛NHLBI最近资助了一项利用儿科急诊护理的多中心III期随机对照试验 应用研究网络（PECARN），PI计划进行确定性研究-镰状细胞病 精氨酸治疗（STArT），以确定ART的疗效和安全性。SCD的疼痛是主要的 急诊室（艾德）就诊和住院的原因，与死亡率增加有关。有 目前没有治疗急性疼痛的潜在机制的疗法，干预措施仅限于水合作用和 analgesia. PI假设ARG是一种安全廉价的营养补充剂， 对患有SCD和疼痛的儿童的影响，在低资源环境中具有潜在价值。STArT试验将 为产品开发提供必要的数据，并最终帮助SCD获得FDA产品批准， ART的益处得到证实。这一提议的结果可能最终导致临床实践的改变 用于SCD患者，目标是NCCIH疼痛非药物管理的战略优先事项。的 PI高度致力于执行POR，专注于营养科学，并将她的指导范围扩大到 包括本科生、医学生、博士后研究员和初级教师，特别是 临床营养研究中的妇女和代表性不足的医生，指导了40多名受训人员 在她的职业生涯中。在5年的资助更新期间，候选人还将参加一些 领导力和导师课程，选择课程，这将有助于提高候选人作为一个教育 学术医学领域的领导者和导师。埃默里大学的环境非常适合培养这些目标 并将促进申请人的职业发展，作为一个导师冠军在综合医学， 与格鲁吉亚临床和转化科学联盟合作，使她能够在该领域培训学员 增加循证综合临床科学家的数量。

项目成果

Mobile phone virtual reality game for pediatric home burn dressing pain management: a randomized feasibility clinical trial.

• DOI: 10.1186/s40814-022-01150-9
• 发表时间: 2022-08-18
• 期刊: PILOT AND FEASIBILITY STUDIES
• 影响因子: 1.7
• 作者: Armstrong, Megan;Lun, Jonathan;Groner, Jonathan, I;Thakkar, Rajan K.;Fabia, Renata;Noffsinger, Dana;Ni, Ai;Keesari, Rohali;Xiang, Henry
• 通讯作者: Xiang, Henry

Pediatric firearm and motor vehicle collision injuries in the United States: Diverging trends.

美国的儿童枪支和机动车辆碰撞伤害：不同的趋势。

• DOI: 10.1016/j.ajem.2021.12.029
• 发表时间: 2022
• 期刊: The American journal of emergency medicine
• 作者: Doh,KieshaFraser;Sheline,EricaK;Wetzel,Martha;Xiang,Yijin;Morris,ClaudiaR;Simon,HaroldK
• 通讯作者: Simon,HaroldK

Resolution of Acute Priapism in Two Children With Sickle Cell Disease Who Received Nitrous Oxide.

两名接受一氧化二氮治疗的镰状细胞病儿童的急性阴茎勃起得到解决。

• DOI: 10.1111/acem.13822
• 发表时间: 2019
• 期刊: Academic emergency medicine : official journal of the Society for Academic Emergency Medicine
• 作者: Greenwald,MichaelH;Gutman,ColleenK;Morris,ClaudiaR
• 通讯作者: Morris,ClaudiaR

Utility of Point-of-Care Lung Ultrasonography for Evaluating Acute Chest Syndrome in Young Patients With Sickle Cell Disease.

床旁肺部超声检查在评估镰状细胞病年轻患者的急性胸部综合征中的实用性。

• DOI: 10.1016/j.annemergmed.2020.08.012
• 发表时间: 2020
• 期刊: Annals of emergency medicine
• 影响因子: 6.2
• 作者: Cohen,StephanieG;Malik,ZayirM;Friedman,Sam;Russell,Stephen;Hagbom,Robert;Alazraki,Adina;McCracken,CourtneyE;Figueroa,Janet;Adisa,OlufolakeA;Mendis,ReshikaD;Manoranjithan,Shaminy;Simon,HaroldK;Morris,ClaudiaR
• 通讯作者: Morris,ClaudiaR

Arginine Therapy and Cardiopulmonary Hemodynamics in Hospitalized Children with Sickle Cell Anemia: A Prospective, Double-blinded, Randomized Placebo-controlled Clinical Trial.

镰状细胞性贫血住院儿童的精氨酸治疗和心肺血流动力学：一项前瞻性、双盲、随机安慰剂对照临床试验。

• DOI: 10.1164/rccm.202108-1930oc
• 发表时间: 2022
• 期刊: American journal of respiratory and critical care medicine
• 影响因子: 24.7
• 作者: Onalo,Richard;Cilliers,Antoinette;Cooper,Peter;Morris,ClaudiaR
• 通讯作者: Morris,ClaudiaR