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.

项目总结/摘要 腹泻引起单价（例如，Na+、K+、Cl-和HCO 3-）和二价（例如，Zn 2+、Ca 2+）离子损失。不像 单价离子的损失很大，因此通过再水化治疗得到补充，二价离子的损失 渗透压摩尔浓度相对较小，在治疗中经常被忽视。研究表明，尽管二价 离子在粪便中贡献相对较少的渗透压摩尔，由于二价离子传感的存在， 受体（例如，Zn 2+敏感受体，ZnSR; Ca 2+敏感受体，CaSR）及其在肠道中的放大作用。作为 结果，这些二价离子的丢失而不被替换可能影响急性腹泻的程度或从急性腹泻中恢复 疾病。如果不补充Zn 2+和恢复ZnSR的抗腹泻功能，腹泻会更严重， 延长;补充Zn 2+和纠正ZnSR缺陷降低腹泻的严重程度和持续时间。这是非常 记录在案。然而，关于Ca 2+和CaSR在腹泻中的作用的信息是有限的。PI的实验室在 佛罗里达大学是第一个报道在人的大脑中存在一种有效的基于Ca 2 +/CaSR的抗衰老机制的人。 胃肠道在实验室动物中证明了Ca 2 +/CaSR在儿童腹泻中的作用后，PI和他的 同事们提出了少数儿童牙周病病例的临床证据。这些对人类的初步研究 表明，像Zn 2+一样，在不纠正负Ca 2+平衡的情况下，腹泻症状更严重或更持久， 并且，随着Ca 2+的替代，动物和人类的腹泻都迅速而显著地减少。基于 基于此，假设理想的腹泻替代疗法将是替代两种单价离子的溶液， 和二价矿物质，特别是Ca 2+。然而，到目前为止，还没有关于钙离子的正式随机对照试验（RCT）。 已在牙周炎患者中进行了更换。这项拟议的研究是这种努力的第一次。在该初始 研究，我们建议获得初步数据，以证明钙离子替代对临床结局的安全性和有效性 （粪便排出量和腹泻持续时间）在成人急性感染性腹泻之前，更强大和昂贵的RCT是 包括在婴儿和幼儿中进行。我们预计，钙离子的迅速取代将显着减少 严重程度和缩短腹泻症状的持续时间。