Maternal Opioid Treatment: Human Experimental Research

描述（由申请人提供）： 大约三分之一的阿片类药物成瘾者是育龄女性。阿片类药物依赖期间的妊娠提出了一系列复杂的治疗挑战。美沙酮是目前推荐用于妊娠阿片类药物依赖妇女的唯一维持药物疗法。美沙酮相对于持续未经治疗的海洛因成瘾或药物戒毒提供了许多好处，但其在怀孕期间的使用仍然存在争议，部分原因是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。与非药物暴露婴儿相比，阿片类药物暴露婴儿的新生儿住院时间更长，费用更高，并显示神经生理和行为障碍。据估计，55%-94%在子宫内暴露于阿片类药物的婴儿会出现阿片类药物戒断的迹象。丁丙诺啡是一种正在接受FDA审查的用于治疗阿片类药物依赖的新药，据报道，在成人突然停药后仅产生轻度戒断综合征。与美沙酮相比，丁丙诺啡在新生儿中产生较少新生儿戒断体征（NAS）的功效将在阿片类药物依赖的孕妇中采用随机、平行组、多中心设计进行评估。范德比尔特大学医学中心和中田纳西治疗中心的多学科小组的专业知识在成瘾医学，精神病学，儿科学，产科学，妇科学和对照临床试验方面得到了培训，为受试者提供了全面的护理，并为研究提供了严格的科学诚信。约翰霍普金斯研究中心将作为本多中心试验的牵头研究中心，涉及6家美国研究中心和2家国际研究中心。将对随机分配至等效阿片类药物剂量美沙酮（N=30）或丁丙诺啡（N=30）的受试者进行妊娠期随访。主要结局指标为NAS、给予的抗戒断药物总量和接受治疗的新生儿数量。次要胎儿/新生儿结局指标为：标准产前测量、无应激试验、生物物理学特征和住院时间（天）。次要孕产妇结局指标包括：治疗保留率、药物使用（包括酒精）的客观和主观指标、总体评估以及剂量充足性和安全性数据。这将是第一项研究，以发展一个基础设施和网络的网站，专门知识进行对照试验与药物滥用和依赖孕妇。利用该网络将确保在难以招募的人群中成功招募研究受试者（即，孕妇）。

DESCRIPTION (provided by applicant): Approximately 1/3 of opioid addicts are women of childbearing age. Pregnancy during opioid dependence presents a complex array of therapeutic challenges. Methadone is the only maintenance pharmacotherapy currently recommended for use in pregnant opioid-dependent women. Methadone offers many benefits relative to continued untreated heroin addiction or medical detoxification, but its use during pregnancy continues to be controversial due in part to the large percentage of newborns having signs of opioid withdrawal requiring medical intervention and extended hospitalization. Compared to nondrug exposed infants, opioid exposed infants have longer and more costly neonatal hospitalizations and display neurophysiological and behavioral disruptions. It is estimated that 55%-94% of infants exposed to opioids in utero will show signs of opioid withdrawal. Buprenorphine, a new medication under FDA review for the treatment of opioid dependence, is reported to produce only a mild abstinence syndrome following abrupt withdrawal in adults. The efficacy of buprenorphine to produce less neonatal abstinence signs (NAS) in the neonate, compared to methadone, will be assessed in opioid-dependent pregnant women utilizing a randomized, parallel group, multi-site design. The professional expertise of a multi-disciplinary group at Vanderbilt University Medical Center and Middle Tennessee Treatment Center trained in addiction medicine, psychiatry, pediatrics, obstetrics, neonatology, and controlled clinical trials has been brought together to provide comprehensive care for the subjects and rigorous scientific integrity for the study. The Johns Hopkins site will act as the Lead Site of this multi-site trial involving six US sites and two International. Subjects randomized to equivalent opioid doses of methadone (N=30) or buprenorphine (N=30) will be followed through pregnancy. Primary outcome measures are NAS, total anti-withdrawal medication given, and number of neonates treated. Secondary fetal/neonatal outcome measures are: standard antenatal measures, non-stress test, biophysical profile, and length (days) of hospital stay. Secondary maternal outcome measures include: treatment retention, objective and subjective measures of drug use including alcohol, global assessments, and dose-adequacy and safety data. This will be the first study to develop an infrastructure and network of sites with expertise in conducting controlled trials with pharmacotherapies for substance abusing and dependent pregnant women. Utilization of this network will ensure the successful accrual of study participants in a difficult to recruit population (i.e., pregnant women).