ENDEAVOR TO STOP NAUSEA/VOMITING ASSOCIATED WITH PREGNANCY (E-SNAP)

努力停止与怀孕相关的恶心/呕吐 (E-SNAP)

• 批准号: 10390898
• 负责人: KATHERINE L WISNER
• 金额: $ 24万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-06-13 至 2024-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10390898
• 关键词: Advisory Committees; Affect; Antidepressive Agents; Antiemetics; Area; Body Weight decreased; Brain; Case Series; Chemotherapy-Oncologic Procedure; Clinical Trials; Cognitive; Congenital Abnormality; Data; Dehydration; Development; Discipline of obstetrics; Dose; Drug Kinetics; Drug Prescriptions; Electrolytes; Enrollment; Exhibits; Formulation; Frequencies; Gastroparesis; General Population; Grant; Hospitalization; Hyperemesis Gravidarum; Impairment; Lactation; Lead; Mental Depression; Mirtazapine; Monitor; Mothers; National Institute of Child Health and Human Development; Nausea; Nausea and Vomiting; Neurodevelopmental Deficit; New Agents; Newborn Infant; Norepinephrine; Ondansetron; Operative Surgical Procedures; Oral; Paper; Parenteral Nutrition; Pathway interactions; Pharmaceutical Preparations; Pharmacogenetics; Pharmacotherapy; Phase; Phase II Clinical Trials; Physiological; Placebos; Plasma; Pregnancy; Pregnancy Outcome; Pregnant Women; Premature Birth; Property; Quality of life; Randomized Controlled Trials; Regimen; Reporting; Research; Research Support; Resolution; Resources; Risk; Safety; Sample Size; Serotonin; Small for Gestational Age Infant; Structure; Symptoms; Therapeutic; Third Pregnancy Trimester; Time; Translational Research; Vomiting; Woman; clinical practice; daily functioning; depressive symptoms; design; drug repurposing; drug standard; effective therapy; efficacy evaluation; experience; improved; inhibitor; multidisciplinary; neonatal outcome; novel; novel therapeutics; offspring; pediatric pharmacology; phase 2 study; prevent; receptor; reduce symptoms; reproductive outcome; reuptake; serotonin receptor; side effect; standard care; systematic review; treatment duration; treatment research; week trial

PROJECT SUMMARY/ABSTRACT ENDEAVOR TO STOP NAUSEA/VOMITING ASSOCIATED WITH PREGNANCY (E-SNAP) Up to 85% of pregnant women experience nausea and vomiting of pregnancy (NVP), which impairs daily function and reduces quality of life. A severe form, hyperemesis gravidarum (HG), affects 0.3-3% of pregnant women and is the most common reason for hospitalization in the first half of pregnancy. Although NVP and HEG usually resolve by mid-pregnancy, symptoms persist into the third trimester in 15--20% of women. HG is associated with preterm birth and small-for gestational age infants as well as termination of desired pregnancies in 14.4% of affected women. Recent studies show that women with severe NVP (sNVP), defined by weight loss or continuation of symptoms beyond 20 weeks gestation, have offspring at risk for structural brain changes and cognitive developmental problems. Despite the frequency and complications of sNVP, only low-quality evidence is available to direct treatment. The NICHD report from the Task Force on Research Specific to Pregnant Women and Lactating Women stated that the drug pipeline for conditions specific to pregnancy is “minimal at best” and listed hyperemesis as an area of need for treatment research. This exploratory/developmental Clinical Trial Planning Grant is a Phase 2 study that will provide data on the acceptability, dose regimen, tolerability and safety of mirtazapine (Remeron®) for the treatment of sNVP that has not responded to at least two standard medications. We will to determine whether a larger randomized controlled trial to evaluate mirtazapine’s efficacy for sNVP is warranted. An FDA application for an IND will be submitted and a DSMB will be constituted. Mirtazapine is prescribed for nausea and vomiting during cancer chemotherapy. Rapid reduction of NVP during mirtazapine treatment has been reported in case series of pregnant women who have not responded to other medications. Mirtazapine impacts the serotonin receptor (similar to ondansetron) as well as three additional receptors involved in the physiologic cascade that results in nausea and emesis. It is a compelling candidate to consider for repurposing to expand therapeutic options for sNVP. Reproductive outcome data for mirtazapine do not indicate an increased risk for birth defects, although the number of women studied is relatively small (≈500). Additionally, pharmacogenetic factors that affect mirtazapine plasma concentrations and thereby affect its tolerability and safety will be considered in the proposed project.

项目摘要/摘要 努力阻止与怀孕相关的恶心/呕吐（E-SNAP） 多达85％ 功能并降低生活质量。严重的形式，过时的妊娠（Hg），影响了0.3-3％的孕妇 妇女，是怀孕上半年住院的最常见原因。虽然NVP和 HEG通常是在怀孕中期解决的，符号在15--20％的女性中持续到三个月。 HG是 与早产和小胎龄相关以及所需的终止 14.4％的受影响妇女的怀孕。最近的研究表明，患有严重NVP（SNVP）的女性定义 通过体重减轻或症状的延续超过20周妊娠，后代有结构性的风险 大脑变化和认知发展问题。 尽管SNVP频率和并发症，但只有低质量的证据可以直接指导 治疗。特定于孕妇的研究小组的NICHD报告和哺乳 妇女说，针对怀孕特定疾病的药物管道“充其量最少”，并列出 高温生是需要治疗研究的领域。 这项探索性/发展性临床试验计划赠款是一项第二阶段研究，将提供有关的数据 Mirtazapine（Remeron®）治疗SNVP的可接受性，剂量方案，耐受性和安全性 这尚未对至少两种标准药物做出反应。我们将确定较大的随机 有必要评估Mirtazapine的SNVP效率的对照试验。 IND的FDA申请将是 已提交，将构成DSMB。 在癌症化学疗法期间，米氮平是针对恶心和呕吐的。快速减少NVP 据报道，在没有回应的孕妇的病例中，已经报道了 其他药物。 Mirtazapine影响5-羟色胺受体（类似于Ondansetron），三个 涉及生理级联反应的其他受体会导致恶心和呕吐。这是一个引人注目的 候选人考虑重新利用以扩展SNVP的治疗选择。生殖结果数据 Mirtazapine并不表示出生缺陷的风险增加，尽管Studiod的女性数量是 相关的小（≈500）。此外，影响米氮平血浆浓度的药物遗传因素 因此，将在拟议的项目中考虑影响其耐受性和安全性。