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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)

基本信息

批准号：
10643818
负责人：
KATHERINE L WISNER
金额：
$ 20万
依托单位：
NORTHWESTERN UNIVERSITY AT CHICAGO
依托单位国家：
美国
项目类别：
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/10643818
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 Marketing Mental Depression Mirtazapine Monitor Morning Sickness Mothers National Institute of Child Health and Human Development Nausea Nausea and Vomiting Neurodevelopmental Deficit New Agents Newborn Infant Norepinephrine Ondansetron 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 patient population pediatric pharmacology phase 2 study prevent receptor reduce symptoms reproductive outcome reuptake serotonin receptor side effect standard care systematic review treatment duration treatment research trial planning week trial

项目摘要

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.

项目总结/摘要奋进终止妊娠相关恶心/呕吐（E-SNAP）高达85%的孕妇经历恶心和呕吐的怀孕（NVP），这损害了每天功能，降低生活质量。妊娠剧吐（HG）是一种严重的形式，影响0.3-3%的孕妇。这是怀孕前半期住院的最常见原因。虽然NVP和 HEG通常在妊娠中期消退，15- 20%的女性症状持续到妊娠晚期。汞与早产和小于胎龄儿以及终止所需的 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妊娠20周，使后代有结构性大脑变化和认知发展问题。尽管sNVP的频率和并发症很高，但只有低质量的证据可供指导治疗NICHD关于孕妇和哺乳期妇女研究特别工作组的报告妇女们表示，针对怀孕特定条件的药物管道“充其量是最少的”，并列出了作为一个需要治疗研究的领域。这项探索性/开发性临床试验计划资助是一项2期研究，将提供以下数据：米氮平（Remeron®）治疗sNVP的可接受性、剂量方案、耐受性和安全性对至少两种标准药物都没有反应我们将确定是否有更大的随机需要进行对照试验来评估米氮平对sNVP的疗效。FDA的IND申请将提交并组建DSMB。米氮平用于治疗癌症化疗期间的恶心和呕吐。NVP快速降低在对米氮平治疗无反应的孕妇的病例系列中，其他药物。米氮平影响血清素受体（类似于昂丹司琼）以及三种参与导致恶心和呕吐的生理级联反应的其他受体。而且是一个引人注目的考虑重新利用以扩大sNVP的治疗选择的候选人。生殖结局数据米氮平并不表明出生缺陷的风险增加，尽管研究的妇女人数是相对较小（约500）。此外，影响米氮平血药浓度的药物遗传学因素从而影响其耐受性和安全性。