Fetal and Infant Effects of Maternal Buprenorphine Treatment

NCT ID: NCT01561079

Last Updated: 2017-09-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 127 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-02-29
• Study Completion Date: 2016-06-30

Brief Summary

This research will track the longitudinal neurobehavioral development of the buprenorphine-exposed fetus across gestation through 1 month of age in an effort to determine the safety of this medication for use during gestation, the relationship between maternal physiologic changes due to buprenorphine administration and newborn functioning, and to determine potential fetal neurobehavioral markers that may predict Neonatal Abstinence Syndrome expression and infant neurobehavioral outcome. Comparisons to results from a similar project in methadone-exposed pregnancies will be made. This proposal seeks to advance the way the investigators inform the treatment of the opioid dependent woman during pregnancy and her infant after birth.

Detailed Description

There is an increase in the prevalence of illicit opiate use among women of childbearing age in many countries today. Methadone is the treatment of choice for opioid dependency during pregnancy in the US because it markedly diminishes withdrawal symptoms and craving and blocks opioid effects, however, in utero exposure results in significant depression of fetal neurobehaviors such as fetal heart rate and heart rate variability and fetal motor activity, and significant neonatal abstinence syndrome (NAS) in the majority of exposed infants. Since its approval in 2002, the prescription of buprenorphine for opioid dependence has increased dramatically but, as with methadone, this mediation is not approved for use during pregnancy. Currently, women treated with buprenorphine prior to pregnancy are transitioned to methadone treatment due to a lack of information regarding the effects of buprenorphine on the developing fetus and infant. Pilot work by this research team suggests that buprenorphine- as compared to methadone-exposed fetuses display more optimal neurobehavioral functioning in the second and third trimesters of pregnancy. Although these results are encouraging, there is a critical need to explore fully the effects of this medication on the fetus and infant to adequately advise care providers and patients regarding its use. This is particularly true given the imminent publication of a pivotal study comparing buprenorphine to methadone treatment during pregnancy which has suggested the optimality of buprenorphine for the treatment of opioid dependence during pregnancy, and is likely to result in increasing numbers of women being treated with off-label buprenorphine during pregnancy. This proposal seeks to explore the effect of buprenorphine on maternal physiology and fetal neurobehavioral functioning longitudinally as a measure of the development of the fetal nervous system. Additionally, the neurobehavioral profile and NAS of the buprenorphine-exposed infant up to one month will be delineated in an effort to provide information necessary to provide optimal pharmacologic and non-pharmacologic treatment of NAS. Furthermore, this group has previously explored similar parameters in methadone-exposed fetuses and infants, and results of this study can be compared to those historical data. These parameters will advance our understanding of the way the investigators view and implement the future pharmacologic treatment of the opiate dependent woman during pregnancy and her infant after birth, and inform clinicians, health insurance companies and regulatory agencies in the provision of optimal care to the opioid dependent pregnant woman and her offspring before and after birth.

Conditions

Neonatal Abstinence Syndrome

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Maternal buprenorphine treatment

Buprenorphine maintenance during pregnancy

Group Type: EXPERIMENTAL

Buprenorphine

Intervention Type: DRUG

Daily sublingual buprenorphine treatment of pregnant, opioid dependent women from up to 34 weeks gestation through one month of infant age.

Interventions

Buprenorphine

Daily sublingual buprenorphine treatment of pregnant, opioid dependent women from up to 34 weeks gestation through one month of infant age.

Intervention Type: DRUG

Other Intervention Names

Subutex

Eligibility Criteria

Inclusion Criteria

• Current opioid dependence as defined by Diagnostic and Statistical Manual of Mental Disorders (DSM) IV-R criteria
• 18-40 years of age with uncomplicated singleton pregnancies
• Accurate gestational age dating verified by ultrasound
• Gestation of less than 34 weeks
• Stabilization on buprenorphine for one week prior to study procedures

Exclusion Criteria

• Complications of pregnancy, including gestational diabetes, polyhydramnios, hypertension, placenta previa or significant risk of preterm delivery (i.e. incompetent cervix)
• Evidence of fetal malformation detected by prenatal ultrasound
• Significant general maternal health problems that can affect fetal functioning, including Type I or gestational diabetes, alterations in thyroid functioning, HIV infection or hypertension.
• Significant maternal psychopathology that would preclude informed consent (i.e. schizophrenia)
• Alcohol dependency per DSM IV R criteria (see ascertainment methods below)
• Women stable on methadone maintenance (defined as more than 3 days of methadone dosing)
• Women entering drug treatment reporting using "street" methadone (for more than 3 days)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 40 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Johns Hopkins University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Lauren M Jansson, MD

Role: PRINCIPAL_INVESTIGATOR

Johns Hopkins University

Locations

Center for Addiction and Pregnancy

Baltimore, Maryland, United States

Johns Hopkins Bayview Medical Center

Baltimore, Maryland, United States

Countries

United States

References

Jansson LM, Dipietro JA, Velez M, Elko A, Williams E, Milio L, O'Grady K, Jones HE. Fetal neurobehavioral effects of exposure to methadone or buprenorphine. Neurotoxicol Teratol. 2011 Mar-Apr;33(2):240-3. doi: 10.1016/j.ntt.2010.09.003. Epub 2010 Sep 22.

Reference Type: BACKGROUND

PMID: 20868741 (View on PubMed)

Velez ML, McConnell K, Spencer N, Montoya L, Tuten M, Jansson LM. Prenatal buprenorphine exposure and neonatal neurobehavioral functioning. Early Hum Dev. 2018 Feb;117:7-14. doi: 10.1016/j.earlhumdev.2017.11.009. Epub 2017 Dec 7.

Reference Type: DERIVED

PMID: 29223912 (View on PubMed)

Other Identifiers

00051600

Identifier Type: -

Identifier Source: org_study_id