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

项目摘要/摘要 努力停止妊娠相关的恶心/呕吐(E-SNAP) 高达85%的孕妇会经历妊娠恶心和呕吐(NVP)，这会对日常生活造成损害 功能和降低生活质量。一种严重的形式，妊娠剧吐(HG)，影响0.3-3%的孕妇 这是孕妇在怀孕前半段住院的最常见原因。尽管NVP和 HEG通常在怀孕中期消失，15%-20%的妇女症状会持续到晚期。HG是 与早产和小于胎龄儿以及所需终止有关 14.4%的受影响妇女怀孕。最近的研究表明，患有严重NVP(SNVP)的女性 体重减轻或症状持续超过20周，会使后代面临结构性疾病的风险 大脑变化和认知发育问题。 尽管sNVP的频率和并发症很多，但只有低质量的证据可以用来指导 治疗。NICHD专门针对孕妇和哺乳期的研究工作组的报告 妇女们表示，针对特定怀孕情况的药物供应“充其量是最低限度的”，并列出了 作为治疗研究需要的领域之一的剧吐。 这项探索性/开发性临床试验计划拨款是一项第二阶段研究，将提供以下数据 米氮平治疗sNVP的可接受性、给药方案、耐受性和安全性 至少有两种标准药物对此没有反应。我们将确定一个更大的随机化 评价米氮平治疗sNVP疗效的对照试验是必要的。FDA的IND申请将是 提交，并将组成一个dsmb。 米氮平是用来治疗癌症化疗期间的恶心和呕吐的。NVP的快速降低 在米氮平治疗期间，已有一系列病例报道对米氮平没有反应的孕妇 其他药物。米氮平影响5-羟色胺受体(类似于恩丹西酮)以及三种 更多的受体参与导致恶心和呕吐的生理学级联反应。这是一个令人信服的 考虑重新调整用途以扩大sNVP的治疗选择的候选人。年的生殖结果数据 米氮平并不表明出生缺陷的风险增加，尽管研究的女性人数是 相对较小(≈500)。此外，影响米氮平血药浓度的药物遗传因素 并由此影响其耐久性和安全性，将在拟建项目中予以考虑。

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.