Maternal Buprenorphine-naloxone Treatment and the Infant

Sponsor

Johns Hopkins University (Other)

Overall Status

Recruiting

CT.gov ID

NCT03291847

Collaborator

National Institute on Drug Abuse (NIDA) (NIH)

Enrollment

Location

Arms

Anticipated Duration (Months)

1.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Maternal Opioid Use Disorder Opioid Exposed Infant	Device: fetal monitoring Drug: Buprenorphine Naloxone Drug: Methadone	Phase 2

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

80 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

One group of n=40 study participants will receive buprenorphine-naloxone medication assisted therapy for the treatment of opioid use disorder during pregnancy, a second group of n=40 will receive methadone as standard of care. Subjects will undergo identical study procedures.One group of n=40 study participants will receive buprenorphine-naloxone medication assisted therapy for the treatment of opioid use disorder during pregnancy, a second group of n=40 will receive methadone as standard of care. Subjects will undergo identical study procedures.

Masking:

None (Open Label)

Primary Purpose:

Basic Science

Official Title:

Maternal Buprenorphine-naloxone Treatment During the Perinatal Period: Fetal and Infant Effects

Actual Study Start Date :

Jun 1, 2018

Anticipated Primary Completion Date :

Dec 1, 2022

Anticipated Study Completion Date :

Dec 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Buprenorphine-naloxone treated Participants receiving buprenorphine-naloxone treatment for opioid use disorder during pregnancy	Device: fetal monitoring Maternal fetal monitoring Other Names: maternal physiology monitoring Drug: Buprenorphine Naloxone Treatment for opioid use disorder Other Names: Suboxone
Active Comparator: Methadone treated Participants receiving methadone treatment for opioid use disorder during pregnancy	Device: fetal monitoring Maternal fetal monitoring Other Names: maternal physiology monitoring Drug: Methadone Treatment for opioid use disorder

Arm

Intervention/Treatment

Experimental: Buprenorphine-naloxone treated

Participants receiving buprenorphine-naloxone treatment for opioid use disorder during pregnancy

Device: fetal monitoring

Maternal fetal monitoring

Other Names:

maternal physiology monitoring

Drug: Buprenorphine Naloxone

Treatment for opioid use disorder

Other Names:

Suboxone

Active Comparator: Methadone treated

Participants receiving methadone treatment for opioid use disorder during pregnancy

Device: fetal monitoring

Maternal fetal monitoring

Other Names:

maternal physiology monitoring

Drug: Methadone

Treatment for opioid use disorder

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

Neonatal abstinence syndrome severity score (NAS)1 [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 [day 2 of life]
Neonatal abstinence syndrome severity score
NAS3 [day 3 of life]
Neonatal abstinence syndrome severity score
NAS4 [day 4 of life]
Neonatal abstinence syndrome severity score

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 44 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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.