Maternal Opioid Treatment: Human Experimental Research

母亲阿片类药物治疗：人体实验研究

• 批准号: 6953116
• 负责人: PETER ROBERT MARTIN
• 金额: $ 52.99万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-27 至 2009-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6953116
• 关键词: blood tests; buprenorphine; clinical research; clinical trials; drug /alcohol abstinence; drug abuse chemotherapy; drug addiction; drug withdrawal; embryo /fetus; embryo /fetus drug adverse effect; female; human fetus tissue; human pregnant subject; human subject; human therapy evaluation; methadone; newborn human (0-6 weeks); opiate alkaloid; outcomes research; patient oriented research; pregnancy; prenatal care; urinalysis; women' s health

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).

描述(由申请人提供)： 大约三分之一的阿片成瘾者是育龄妇女。阿片类药物依赖期间怀孕带来了一系列复杂的治疗挑战。美沙酮是目前推荐用于怀孕阿片依赖妇女的唯一维持药物疗法。与持续的未经治疗的海洛因成瘾或药物戒毒相比，美沙酮提供了许多好处，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迹象，需要医疗干预和延长住院时间。与未接触药物的婴儿相比，暴露于阿片类药物的婴儿住院时间更长，费用更高，并表现出神经生理和行为障碍。据估计，在子宫内接触阿片类药物的婴儿中，55%-94%会出现阿片类药物戒断的迹象。丁丙诺啡是FDA审查的一种治疗阿片类药物依赖的新药，据报道，在成年人突然戒断后，它只会产生轻度戒断综合征。丁丙诺啡与美沙酮相比，在新生儿中产生较少新生儿禁欲迹象(NAS)的疗效将使用随机、平行组、多点设计在阿片类药物依赖孕妇中进行评估。范德比尔特大学医学中心和田纳西州中部治疗中心的多学科小组在成瘾医学、精神病学、儿科、产科、新生儿学和受控临床试验方面接受过培训，他们的专业知识被整合在一起，为受试者提供全面的护理，并为研究提供严格的科学诚信。约翰霍普金斯大学的网站将作为这项涉及6个美国网站和2个国际网站的多网站试验的牵头网站。随机接受同等剂量阿片类药物美沙酮(N=30)或丁丙诺啡(N=30)的受试者将在整个怀孕期间进行跟踪观察。主要的观察指标是NAS、给予的总的抗戒断药物以及接受治疗的新生儿数量。二次胎儿/新生儿结局指标包括：标准产前检查、非应激试验、生物物理指标和住院天数。次级孕产妇结果衡量标准包括：治疗保留、包括酒精在内的药物使用的客观和主观衡量标准、全球评估以及剂量充分性和安全性数据。这将是建立基础设施和网站网络的第一项研究，这些网站具有对药物滥用和依赖孕妇进行药物治疗的对照试验的专门知识。利用这一网络将确保在难以招募的人群(即怀孕妇女)中成功地积累研究参与者。