Safety, pharmacokinetics and efficacy of extended-release naltrexone in pregnant women with opioid use disorder

缓释纳曲酮对阿片类药物使用障碍孕妇的安全性、药代动力学和疗效

• 批准号: 10178062
• 负责人: Elisha Wachman
• 金额: $ 62.44万
• 依托单位: BOSTON MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-17 至 2023-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10178062
• 关键词: Adverse effects; Aftercare; Age-Months; Agonist; Alleles; Animals; Biological Assay; Birth; Blood; Boston; Brain; Breast Feeding; Buprenorphine; Caring; Cohort Studies; DNA Methylation; Data; Development; Dose; Drug Kinetics; Effectiveness; Enrollment; Epigenetic Process; Excretory function; Exposure to; Female of child bearing age; Fetal Development; Fetal Distress; Fetus; Future; Genes; Genetic; Genomics; Growth; Hour; Human; Human Milk; Hydrocortisone; Infant; Investigation; Kidney; Knowledge; Lactation; Left; Life; Measures; Medical Societies; Medical center; Metabolism; Methadone; Methylation; Modification; Monitor; Mothers; Naltrexone; Names; Neonatal Abstinence Syndrome; Neurodevelopmental Impairment; North Carolina; Opiate Addiction; Opioid; Opioid Antagonist; Opioid agonist; Outcome; Overdose; Patients; Pharmaceutical Preparations; Pharmacogenetics; Pharmacogenomics; Placenta; Plasma; Policy Maker; Postpartum Period; Postpartum Women; Pregnancy; Pregnancy Outcome; Pregnant Women; Premature Labor; Prospective cohort study; Provider; Public Health; Receptor Gene; Relapse; Risk; Safety; Saliva; Single Nucleotide Polymorphism; Special Population; Time; Umbilical Cord Blood; Uncertainty; Universities; Urine; Woman; addiction; buprenorphine treatment; common treatment; comparative; effective therapy; fetal; genetic variant; genome wide methylation; genome-wide; human data; improved; individualized medicine; infant outcome; maternal outcome; medication-assisted treatment; mu opioid receptors; neonatal outcome; neurodevelopment; novel; opioid agonist therapy; opioid epidemic; opioid use disorder; optimal treatments; patient population; placental transfer; pre-clinical; pregnant; prenatal exposure; prepregnancy; promoter; prospective; safety study; social; standard of care; success

PROJECT ABSTRACT Opioid use disorders (OUDs) in pregnancy are a US public health crisis; current standard of care is treatment with an opioid agonist such as buprenorphine (BPH), shown to improve pregnancy outcomes however with an associated risk for neonatal abstinence syndrome (NAS) and possible long-term neurodevelopmental consequences. The opioid antagonist naltrexone represents a novel treatment option for OUD in pregnancy which would not expose the developing fetus to opioids, greatly reducing the risk for NAS and potentially improving maternal and infant outcomes. Preliminary animal and human studies demonstrate minimal impact on pregnancy and fetal outcomes with naltrexone exposure, however there is an overall lack of prospective human data fully evaluating safety, efficacy, and the full-range of maternal and infant outcomes. In addition, the pharmacokinetics, pharmacogenomics, placental transfer, breast milk transfer and safety of naltrexone when used during pregnancy and the postpartum period are unknown. We propose to fill these gaps in knowledge by studying the safety, efficacy, pharmacokinetics, and pharmacogenomics of naltrexone for pregnant women with OUDs, evaluating comprehensive mother-infant outcomes throughout the pregnancy and first year after birth. We will enroll 50 pregnant women stabilized pre-pregnancy on extended-release naltrexone (XR-NTX) and 50 comparison women on BPH from Boston Medical Center and the University of North Carolina in this multi-centered prospective comparative cohort study. The specific aims of this project are: 1) Safety and Efficacy: To compare maternal outcomes (safety, relapse, retention in care), fetal outcomes (growth, fetal distress), and infant outcomes (NAS, growth, neurodevelopment) during pregnancy until 12 months post- delivery; 2) Pharmacokinetics: To determine the pharmacokinetics of XR-NTX in pregnant and postpartum women; 3) Genomics: To examine the association between genetic variants and epigenetic modification in the mu-opioid receptor (OPRM1) gene, as well as global DNA methylation changes after treatment with XR-NTX and BPH within the mother, placenta, and infant; and 4) Breast milk: To measure breast milk concentrations of XR-NTX and corresponding infant relative dose to determine safety for lactating women. We hypothesize that XR-NTX will be demonstrated to be a safe and effective treatment option for pregnant and postpartum women with OUD, with improved maternal and infant outcomes in comparison with opioid agonist treatment. The results of this study hold the promise to guide planned future studies examining the use of both XR-NTX and other agonist medications in the context of best practice treatment for OUD in pregnancy in order to improve long-term maternal and infant outcomes.

项目摘要