CLINICAL TRIAL: MOTHER

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 尽管美沙酮显然是有益的，但在怀孕期间使用美沙酮仍然存在争议，部分原因是很大比例的新生儿有阿片类药物戒断的迹象，需要医疗干预和延长住院时间。美国食品和药物管理局(FDA)批准了一种名为丁丙诺啡的新药，用于治疗非怀孕的阿片依赖患者，在突然停药后只会产生轻微的戒断综合征。约翰斯·霍普金斯医学院(JHUSOM)的一项双盲随机试验的初步数据显示，与美沙酮相比，丁丙诺啡可以改善分娩结局，减少新生儿禁欲症状(NAS)。目前的随机平行分组研究是第一个评估丁丙诺啡相对于美沙酮在阿片类药物依赖孕妇中减少NAS疗效的多点试验。佛蒙特州大学(UVM)的网站将与其他四个美国网站和两个国际网站一起参加由JHUSOM牵头的多站点试验。为此，我们汇集了一支在精神病学、成瘾医学、产科、新生儿科学和研究方法方面接受过培训的多学科团队，他们具有专业知识，为参与者提供全面的护理和严谨的科学知识，以进行研究。UVM现场的阿片依赖孕妇将被纳入我们的综合临床研究中心(GCRC)，为期约三天，以进行资格筛选。符合参加条件的患者将随机接受美沙酮(n=24)或丁丙诺啡(n=24)治疗。在GCRC住院约三天的情况下，也将引入双盲、双模拟研究药物，以提供严格的科学控制并最大限度地提高参与者的安全性。在研究的其余部分，药物管理和其他治疗服务将在我们的门诊治疗诊所进行。参与者将在整个怀孕期间接受跟踪，治疗组将在以下主要结果指标上进行比较：NAS总分最高；接受NAS治疗的新生儿数量；接受NAS治疗的新生儿服用的抗戒断药物总量；头围；以及新生儿住院时间。二次新生儿/胎儿结局测量包括其他生理、行为和安全参数。次要的孕产妇结果包括治疗保留、药物使用、用药安全性、心理社会功能和剂量充分性。UVM网站拥有独特的专业知识、经验、设施和资源，包括GCRC，为这一新的潜在网络做出贡献，该网络旨在在难以招募的人群(即吸毒孕妇)中进行临床试验。总体而言，这项研究将为FDA提供关键数据，以支持孕期使用丁丙诺啡的适应症，并可能优化安全有效地治疗怀孕阿片依赖妇女的策略。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Though clearly beneficial, the use of methadone during pregnancy remains controversial due in part to the large percentage of newborns having signs of opioid withdrawal requiring medical intervention and extended hospitalization. A new medication, buprenorphine, is approved by the Food and Drug Administration (FDA) for the treatment of non-pregnant opioid-dependent patients and produces only a mild abstinence syndrome following abrupt withdrawal. Promising preliminary data from a double-blind randomized trial at the Johns Hopkins School of Medicine (JHUSOM) suggest that buprenorphine results in improved birth outcomes and fewer neonatal abstinence signs (NAS) relative to methadone. The current randomized, parallel group study is the first multi-site trial to assess the efficacy of buprenorphine for reducing NAS relative to methadone in opioid-dependent pregnant women. The University of Vermont (UVM) site will participate in the multi-site trial lead by JHUSOM along with four other U.S. and two international sites. To do so, we have brought together a multidisciplinary team trained in psychiatry, addiction medicine, obstetrics, neonatology and research methodology with the professional expertise to provide comprehensive care for the participants and rigorous scientific expertise to conduct the study. Opioid-dependent pregnant women at the UVM site will be admitted to our General Clinical Research Center (GCRC) for approximately three days to be screened for eligibility. Those eligible to participate will be randomized to receive either methadone (n=24) or buprenorphine (n=24). Induction onto double-blind, double-dummy study medications will also occur as inpatient admissions to the GCRC for approximately another three days to provide rigorous scientific control and maximize participant safety. For the remainder of the study, medication administration and other treatment services will occur at our outpatient treatment clinic. Participants will be followed throughout pregnancy and treatment groups will be compared on the primary outcome measures of peak total NAS score; number of neonates treated for NAS; total amount of anti-withdrawal medication given to neonates treated for NAS; head circumference; and neonatal length of hospital stay. Secondary neonatal/fetal outcome measures include other physical, behavioral and safety parameters. Secondary maternal outcomes include treatment retention, drug use, medication safety, psychosocial functioning and dose adequacy. The UVM site has unique expertise, experience, facilities and resources, including the GCRC, to contribute to this new potential network designed to conduct clinical trials in a difficult to recruit population (i.e., drug-abusing pregnant women). Overall, this study will provide pivotal data to the FDA to support an indication for the use of buprenorphine during pregnancy and potentially optimize strategies for safe and effective treatment of pregnant opioid-dependent women.