Pharmacologically-based Strategies for Opioid Substitution Therapy During Pregnancy

Pregnancy Clinical Trial

Official title: Pharmacologically-based Strategies for Opioid Substitution Therapy During Pregnancy

Status Recruiting

Clinical Trial Summary

This study will evaluate maternal tolerance to several BUP dose reduction strategies.

Clinical Trial Description

Opioid use has reached a staggering level and the associated deaths, neonatal consequences and economic impact are devastating. Pregnancy provides a window of opportunity for women with an opioid use disorder (OUD) to seek assistance by participating in a program that offers medication-assisted treatment (MAT), most commonly with buprenorphine (BUP) or methadone. BUP offers advantages over methadone including ease of administration and less severe neonatal abstinence syndrome (NAS) but has a higher discontinuation rate, especially during induction. The high discontinuation rate may be due to an inadequate dosing as the current dosing strategies are not informed by pharmacokinetic (PK) or pharmacodynamic (PD) data in pregnancy. The lack of BUP PD data hampers development of an effective dosing strategy and challenges the validity of the primary tools used to gauge maternal and infant withdrawal. Neither the Clinical Opioid Withdrawal Scale (COWS) nor the Finnegan score for the diagnosis of NAS considers the pharmacology of BUP and therefore may not provide a valid representation of opioid withdrawal. BUP PD data are critically necessary to address these issues and are also necessary to develop detoxification regimens. Creation of safe and effective detoxification regimens requires a pharmacological basis and must be developed in the context that the brain requires time to adjust to opioid induced changes. In this proposal, investigators hypothesize that determination of BUP pharmacodynamics will improve care for the pregnant opioid dependent mother and her baby and will fill the critical knowledge gaps needed for safe and effective management of women with an OUD. For opioid using women, the diagnosis of NAS is viewed as one of the key outcomes to be identified since those infants will need treatment for their perceived withdrawal. Neonatal withdrawal, however, is likely a surrogate for fetal exposure to opioids and not an optimal means of identifying the long-term effects of opioid exposure. The focus on the diagnosis of NAS ignores the importance and risks of opioid exposure on the brain of the infant without NAS. Neuroimaging of the fetal and neonatal brain and neurodevelopmental studies of all infants exposed to opioids, whether or not they are diagnosed as having NAS, will provide tangible long-term measures of the effect of opioids. The relationship between fetal in utero exposure and neonatal outcomes will be explored using maternal and baby hair, placenta, cord and meconium as indicators of chronic maternal and fetal exposure as these are unaffected by maternal truthfulness or acute dosing at the time of delivery. We will relate these indicators of opioid exposure to NAS, as well as to the neuroanatomic and neurodevelopmental outcomes of opioid exposed infants. As part of the dose reduction clinical trial, investigators will compare dose reduction strategies for BUP in pregnancy that are based on the pharmacodynamic and pharmacokinetic characteristics of BUP. The dose reduction strategies that will be evaluated in this clinical trial are part of a larger project including an observational study. ;

Related Conditions & MeSH terms

• Opiate Addiction
• Opioid-Related Disorders
• Pregnancy

• NCT number: NCT03831113
• Study type: Interventional
• Source: University of Pittsburgh
• Contact: Donna DeAngelis, BS
• Phone: 4126414258
• Email: deangelisd@UPMC.edu
• Status: Recruiting
• Phase: Phase 2
• Start date: April 13, 2019
• Completion date: May 31, 2024