Next generation ORS: Randomized controlled trial comparing ORS with calcium vs standard ORS in reducing severity of adults with acute watery diarrhea

下一代 ORS：比较 ORS 加钙与标准 ORS 在降低成人急性水样腹泻严重程度方面的随机对照试验

• 批准号: 10593311
• 负责人: Sam X Cheng
• 金额: $ 28.54万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-01-06 至 2024-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10593311
• 关键词: Acquired Immunodeficiency Syndrome; Acute; Acute Diarrhea; Adopted; Adult; Affect; Africa; Age; Animals; Antibiotics; Antidiarrheals; Azithromycin; Back; Bangladesh; Bicarbonates; Body Weight; COVID-19; Calcium; Calcium-Sensing Receptors; Cause of Death; Cessation of life; Child; Childhood; Cholera; Clinical; Control Groups; Country; Data; Defect; Dehydration; Diarrhea; Dysentery; Ebola; Electrolytes; Emergency department visit; Enrollment; Equilibrium; Facilities and Administrative Costs; Failure; Family; Feces; Florida; Gastrointestinal tract structure; Hospital Costs; Hour; Human; Hydration status; Infant; Infection; Intestines; Intravenous; Ions; Laboratories; Laboratory Animals; Liquid substance; Malaria; Measles; Metabolic; Minerals; Morbidity - disease rate; Oral; Oral Examination; Outcome; Outpatients; Output; Patients; Policies; Public Health; Randomized; Randomized, Controlled Trials; Recommendation; Recovery; Rehydration Solutions; Rehydrations; Replacement Therapy; Reporting; Role; Safety; Severities; Symptoms; Testing; Time; UNICEF; United States; Universities; Vibrio cholerae; Visit; Weight; diarrheal disease; emerging pathogen; mortality; next generation; novel; pandemic disease; participant enrollment; pediatric patients; receptor; restoration; treatment group; trial comparing

Project Summary / Abstract Diarrhea causes monovalent (e.g., Na+, K+, Cl- and HCO3-) and divalent (e.g., Zn2+, Ca2+) ion losses. Unlike the losses of monovalent ions which are large and are therefore replaced through rehydration therapy, the losses of divalent ions are relatively small in osmoles and are often overlooked during diarrheal treatment. Studies now suggest that despite divalent ions contributing relatively few osmoles in the stool, their effects are large due to the presence of divalent ion-sensing receptors (e.g., Zn2+-sensing receptor, ZnSR; Ca2+-sensing receptor, CaSR) and their amplifying effects in the gut. As a result, losses of these divalent ions without replacement may affect the magnitude of, or recovery from acute diarrheal illnesses. Without replacement of Zn2+ and restoration of ZnSR anti-diarrheal function, diarrhea is more severe and protracted; adding back Zn2+ and correcting ZnSR defect reduce the severity and duration of diarrhea. This is well documented. However, information on the role of Ca2+ and CaSR in diarrhea is limited. The PI’s laboratory at the University of Florida was the first to report the presence of a potent Ca2+/CaSR-based antidiarrheal mechanism in the gastrointestinal tract. After demonstrating Ca2+/CaSR action in childhood diarrhea in laboratory animals, the PI and his coworkers presented clinical evidence in few cases of children with diarrheal diseases. These preliminary studies in humans show that, like Zn2+, without correcting negative Ca2+ balance, diarrheal symptoms were more severe or more protracted and that, with replacement of Ca2+, diarrhea was both promptly and dramatically reduced in both animals and humans. Based on this, it is hypothesized that an ideal diarrhea replacement therapy will be a solution that replaces both monovalent ions and divalent minerals, particularly Ca2+. However, so far, no formal randomized controlled trials (RCTs) on Ca2+ replacement in diarrheal patients have been performed. This proposed study represents the first of such efforts. In this initial study, we propose to obtain pilot data to demonstrate the safety and effect size of Ca2+ replacement on clinical outcomes (stool output and diarrhea duration) in adults with acute infectious diarrhea before more powerful and expensive RCTs are conducted, including in infants and young children. We anticipate that prompt replacement of Ca2+ will significantly reduce the severity and shorten the duration of diarrhea symptoms.

项目概要/摘要 与腹泻不同，腹泻会导致单价（例如 Na+、K+、Cl- 和 HCO3-）和二价（例如 Zn2+、Ca2+）离子损失。 一价离子的损失很大，因此可以通过补液疗法补充，二价离子的损失 渗透压相对较小，并且在腹泻治疗期间经常被忽视。现在的研究表明，尽管是二价的。 离子在粪便中贡献的渗透压相对较少，但由于二价离子感应的存在，其影响很大 受体（例如 Zn2+ 敏感受体，ZnSR；Ca2+ 敏感受体，CaSR）及其在肠道中的放大作用。 结果，这些二价离子的损失而不补充可能会影响急性腹泻的严重程度或恢复。 如果不补充 Zn2+ 并恢复 ZnSR 的抗腹泻功能，腹泻会更加严重。 延长；添加 Zn2+ 并纠正 ZnSR 缺陷可以减少腹泻的严重程度和持续时间。 然而，关于 Ca2+ 和 CaSR 在腹泻中的作用的信息有限。 佛罗里达大学率先报道了基于 Ca2+/CaSR 的有效止泻机制 在实验动物中证明了 Ca2+/CaSR 对儿童腹泻的作用后，PI 和他的同事 同事们提供了一些患有腹泻病的儿童的临床证据，这些初步研究是针对人类的。 表明，与 Zn2+ 一样，如果不纠正 Ca2+ 负平衡，腹泻症状会更严重或更持久 并且，通过补充 Ca2+，动物和人类的腹泻都迅速显着减少。 对此，人们再次认识到，腹泻理想的替代疗法将是替代两种单价离子的解决方案 和二价矿物质，特别是 Ca2+ 然而，到目前为止，还没有关于 Ca2+ 的正式随机对照试验 (RCT)。 这项拟议的研究是此类研究中的第一项。 研究中，我们建议获得试点数据来证明 Ca2+ 替代的安全性和对临床结果的影响大小 在更强大和更昂贵的随机对照试验出现之前，对患有急性感染性腹泻的成人进行（粪便排出量和腹泻持续时间） 进行，包括在婴儿和幼儿中，我们预计及时补充 Ca2+ 将显着减少。 腹泻症状的严重程度并缩短其持续时间。