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.

此K24更新申请名为“精氨酸（ARG）缺乏症的“面向患者的研究（POR）” 综合症”为维持原则研究者（PI）的保护时间寻求5年的额外支持 指导活动，促进她的职业发展并提供持续的势头，以推动申请人的 研究评估镰状细胞疾病（SCD）及以后的ARG疗法的研究。 ARG是一种营养补充剂 强制性底物生产一氧化氮，这是一种潜在的血管扩张剂，在发作中加深了 与SCD相关的疼痛。 Pi＆她的男性已经完成了几个随机，双盲的安慰剂 - SCD和疼痛儿童的ARG疗法对照试验（RCT），在美国都需要住院 尼日利亚。这些研究结合在一起发现，ARG替代疗法（ART）具有阿片类药物的影响， 改善疼痛评分和心肺功能，改善止痛药物使用和危机时间分辨率 与安慰剂相比，与较短的医院住院相关。 PI及其同事也观察到 剂量依赖性的ART影响改善了线粒体功能并改善儿童的氧化应激 与scd-pain。随着NHLBI的最新资金，用于多中心阶段3 RCT，利用小儿急诊护理 应用研究网络（PECARN），PI计划进行确定的研究 - 镰状细胞疾病 用精氨酸治疗（开始）来确定艺术的效率和安全性。 SCD疼痛是领先的 急诊室（ED）访问和住院的原因，与死亡率提高有关。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和 镇痛。 PI假设ARG是一种安全且廉价的营养补充剂 SCD和疼痛儿童的影响，在低资源环境中具有潜在价值。开始审判将 提供产品开发的基本数据，并最终将有助于获得SCD的FDA产品批准 确认艺术的好处。该提案的结果最终可能导致临床实践的变化 对于患有SCD的患者，并针对非药物管理疼痛的NCCIH战略优先级。这 Pi高度致力于表演专注于营养科学的POR，并将她的精神职责发展到 包括一群潜水员的本科生，医学生，博士后研究员和初级教师，尤其是 临床营养研究中的妇女和代表性不足的医生在指导了40多名学员 在她的职业生涯中。在5年的赠款续签期间，候选人还将参加多个 领导力与心态课程，选择课程，可以帮助候选人作为教育 学术医学领导者和导师。埃默里大学的环境非常适合促进这些目标 并将提高申请人的职业发展，成为综合医学的心理拥护者 与佐治亚州临床与转化科学联盟的合作伙伴关系，使她能够在现场训练月经 并增加基于证据的综合临床科学家。

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

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

Upward Trends of Parotitis and Mumps in Atlanta over a Decade.

• DOI: 10.1177/2333794x20968676
• 发表时间: 2020
• 期刊: Global pediatric health
• 影响因子: 2.2
• 作者: Reddy LM;Bloch D;Mallino A;Kumari P;Figueroa J;Kendrick L;Chahroudi A;Tuttle J;Thomas E;Morris CR
• 通讯作者: Morris CR

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