Maternal Buprenorphine-naloxone Treatment and the Infant

Overview

The purpose of this mechanistic study is to evaluate the effects that maternal buprenorphine-naloxone maintenance have on the neurobehavioral development of the fetus and infant. To accomplish this, the investigators will study a sample of 120 opioid dependent pregnant women that will receive buprenorphine-naloxone as part of substance abuse treatment at a comprehensive care treatment facility for pregnant and parenting women with substance use disorders. Fetal neurobehavior and maternal physiology will be assessed, via an established maternal-fetal data acquisition system, at 4 points during gestation: 24, 28, 32 and 36 weeks. Infant birth parameters and Neonatal Abstinence Syndrome (NAS) spectrum display will be evaluated at birth, and infant neurodevelopment will be assessed during the first month of life. The investigators will compare the neurodevelopment of the buprenorphine-naloxone-exposed fetuses and infants to that of methadone and buprenorphine-only exposed fetuses and infants.

Full Title of Study: “Maternal Buprenorphine-naloxone Treatment During the Perinatal Period: Fetal and Infant Effects”

Study Type

• Study Type: Interventional
• Study Design
  • Allocation: Non-Randomized
  • Intervention Model: Parallel Assignment
  • Primary Purpose: Basic Science
  • Masking: None (Open Label)
• Study Primary Completion Date: December 27, 2022

Detailed Description

The project population will be 80 pregnant women with opioid use disorder, 40 inducted as outpatients to buprenorphine-naloxone maintenance, and 40 matched methadone controls. Subject treatment data, including medical and obstetric histories, drug use histories, demographic information and psychosocial information will be extracted from patient charts. Weekly urine toxicology testing will provide information regarding other substance use/misuse during the time of study participation. Study participants will undergo 2 60 minute maternal and fetal neurophysiologic monitoring sessions on one day at 4 points during gestation: 24, 28, 32 and 36 weeks, at times of trough (just before sublingual buprenorphine-naloxone or methadone daily dose) and peak (2 1/2 hours after dosing) maternal drug levels. Fetal cardiac (heart rate, heart rate variability, heart rate accelerations) and movement (total fetal movement, number and duration of movement bouts) and the correlation between the two (fetal heart rate-movement coupling) will be determined. Maternal physiologic measures will include heart period and variability, vagal tone, skin conductance and respiratory data. All maternal and fetal measures, with the exception of blood pressure, will be computed in 1-minute intervals and averaged over the 60 min recording. Infant birth data and birth parameters, and neonatal abstinence syndrome scores will be extracted from patient charts. Infants will undergo neurobehavioral testing using the Neonatal Intensive Care Unit (NICU) Network Neurobehavioral Scale, a 30 minute harmless assessment of infant functioning, on days 3, 14 and 30 of life.

Interventions

• Device: fetal monitoring
  • Maternal fetal monitoring
• Drug: Buprenorphine Naloxone
  • Treatment for opioid use disorder
• Drug: Methadone
  • Treatment for opioid use disorder

Arms, Groups and Cohorts

• Experimental: Buprenorphine-naloxone treated
  • Participants receiving buprenorphine-naloxone treatment for opioid use disorder during pregnancy
• Active Comparator: Methadone treated
  • Participants receiving methadone treatment for opioid use disorder during pregnancy

Clinical Trial Outcome Measures

Primary Measures

• Fetal Heart Rate (FHR) 24
  • Time Frame: 24 weeks of gestation
  • Fetal heart rate in msec, mean over 60 minutes gestation
• FHR28
  • Time Frame: 28 weeks of gestation
  • Fetal heart rate in msec, mean over 60 minutes gestation
• FHR32
  • Time Frame: 32 weeks of gestation
  • Fetal heart rate in msec, mean over 60 minutes
• FHR36
  • Time Frame: 36 weeks of gestation
  • Fetal heart rate in msec, mean over 60 minutes

Secondary Measures

• Neonatal abstinence syndrome severity score (NAS)1
  • Time Frame: day 1 of life
  • NAS lists 21 symptoms most frequently observed in opiate-exposed infants. Baseline score is recorded two hours after birth or admission to the nursery. If the infant’s score at any scoring interval is ≥ 8, scoring is increased to 2-hourly and continued for 24 hours from the last total score of 8 or higher. If the 2-hourly score is ≤ 7 for 24 hours then 4-hourly scoring intervals may be resumed. If pharmacotherapy is not needed the infant is scored for the first 4 days of life at 4-hourly intervals. If pharmacotherapy is required the infant is scored at 2- or 4-hourly intervals, depending on whether the abstinence score is less than or greater than 8 throughout the duration of therapeutic period. If after cessation of pharmacotherapy the score is less than 8 for the following 3 days, scoring may be discontinued.
• NAS2
  • Time Frame: day 2 of life
  • Neonatal abstinence syndrome severity score
• NAS3
  • Time Frame: day 3 of life
  • Neonatal abstinence syndrome severity score
• NAS4
  • Time Frame: day 4 of life
  • Neonatal abstinence syndrome severity score

Participating in This Clinical Trial

Inclusion Criteria

• Current opioid use disorder (OUD) as defined by DSM V criteria – singleton pregnancies, generally uncomplicated by conditions that jeopardize pregnancy outcome – Gestation less than 24 weeks Exclusion Criteria:

• Complications of pregnancy, including gestational diabetes, polyhydramnios, hypertension, placenta previa or significant risk of preterm delivery; – 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; – Alcohol use disorder per DSM V criteria (see ascertainment methods below) – Women stable on methadone maintenance (defined as more than 3 consecutive days of dosing) – Women coming to treatment reporting "street" methadone use (for more than 3 consecutive days – Women not planning to receive obstetric care at the Center for Addiction and Pregnancy; – Women not planning to deliver their infants at Johns Hopkins Bayview Medical center – Women planning for adoption of their infant.

Gender Eligibility: Female

Pregnant women with opioid use disorder

Minimum Age: 18 Years

Maximum Age: 44 Years

Are Healthy Volunteers Accepted: No

Investigator Details

• Lead Sponsor
  • Johns Hopkins University
• Collaborator
  • National Institute on Drug Abuse (NIDA)
• Provider of Information About this Clinical Study
  • Sponsor
• Overall Official(s)
  • Lauren M Jansson, MD, Principal Investigator, Johns Hopkins University
• Overall Contact(s)
  • Lauren M Jansson, MD, 410-550-5438, ljansson@jhmi.edu