MOTHER

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。尽管在怀孕期间使用美沙酮明显有益，但仍存在争议，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）批准了一种新的药物丁丙诺啡，用于治疗非怀孕的阿片类药物依赖患者，在突然停药后只会产生轻微的戒断综合征。约翰霍普金斯医学院（JHUSOM）的一项双盲随机试验的初步数据表明，丁丙诺啡与美沙酮相比，可以改善分娩结果，减少新生儿戒断症状（NAS）。目前的随机、平行组研究是第一个评估丁丙诺啡相对于美沙酮降低阿片类药物依赖孕妇NAS疗效的多站点试验。佛蒙特大学（UVM）将与其他四个美国和两个国际站点一起参加JHUSOM领导的多站点试验。为此，我们汇集了一支在精神病学、成瘾医学、产科、新生儿学和研究方法方面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，并具有严谨的科学知识来开展这项研究。UVM站点的阿片类药物依赖孕妇将进入我们的一般临床研究中心（GCRC）进行大约三天的资格筛选。符合条件的参与者将被随机分配接受美沙酮（n=24）或丁丙诺啡（n=24）。GCRC的住院患者也将接受双盲、双假研究药物的诱导，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。在剩余的研究中，药物管理和其他治疗服务将在我们的门诊治疗诊所进行。参与者将在整个妊娠期间进行随访，并对治疗组的主要结局指标NAS总评分进行比较；新生儿NAS治疗人数；新生儿NAS治疗的抗戒断药物总用量；头围;以及新生儿的住院时间。继发性新生儿/胎儿结局测量包括其他身体、行为和安全参数。产妇的次要结局包括治疗保留、药物使用、用药安全、社会心理功能和剂量充足。UVM站点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。总的来说，这项研究将为FDA提供关键数据，以支持怀孕期间使用丁丙诺啡的适应症，并有可能优化安全有效治疗怀孕阿片类药物依赖妇女的策略。

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.