Clinical trial NCT03718104: MOM NEST Study: Maternal Opioid Medication: Naltrexone Efficacy Study
Official title: Safety, Efficacy, Pharmacokinetics, and Pharmacogenomics of Extended-Release Naltrexone in Pregnant Women
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Opioid-use Disorder
Neonatal Abstinence Syndrome
Pregnancy, High Risk
Alcohol Use Disorder
Keywords: naltrexone
buprenorphine/naloxone
maternal relapse
retention in care
pharmacokinetics
pharmacogenetics
Lead sponsor: Boston Medical Center
Sponsor class: OTHER
Collaborators: name: University of North Carolina
name: University of California, San Diego
name: Boston University
name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
First posted: 2018-10-24
Enrollment: 46
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Pregnant women with opioid use disorder or alcohol use disorder on prescribed naltrexone, or those with opioid use disorder on buprenorphine/naloxone and their infants.

Brief summary: This is a multi-center prospective comparative cohort study examining the safety, efficacy, pharmacokinetics, and pharmacogenomics of naltrexone for pregnant women with opioid use disorder. Pregnancy, delivery, and maternal and infant outcomes to 12 months post-delivery will be examined and compared with a cohort treated with buprenorphine/naloxone.

Detailed description: Fifty pregnant women stabilized pre-pregnancy on oral or extended-release naltrexone (XR-NTX) and 50 comparison women on buprenorphine/naloxone (BPH) from Boston Medical Center and the University of North Carolina will be enrolled in this multi-center 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 (neonatal abstinence syndrome, growth, neurodevelopment) during pregnancy until 12 months post- delivery; An exploratory part of this aim is to collect safety and efficacy data on women receiving NTX for alcohol use disorder (AUD). We will collect maternal, fetal and infant outcomes related to prenatal alcohol exposure. 2) Pharmacokinetics: To determine the pharmacokinetics of NTX in pregnant and postpartum women; 3) Genetics and Epigenetics: 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 NTX and BPH within the mother, placenta, and infant; and 4) Breast milk: To measure breast milk concentrations of NTX and corresponding infant relative dose to determine safety for lactating women.

Eligibility criteria: Inclusion Criteria:

* Pregnant women between 6 - 30 6/7 weeks gestation, receiving prenatal care at Boston Medical Center (BMC) or the University of North Carolina (UNC)
* Plan to deliver infant at BMC or UNC
* Diagnosis of opioid use disorder (OUD) or alcohol use disorder (AUD) in the current pregnancy on prescribed oral or extended-release naltrexone; or buprenorphine/naloxone for the treatment of OUD
* English speaking
* Singleton pregnancy

Exclusion Criteria:

* OUD on prescribed methadone, or no maintenance medication
* OUD on Subutex formulation of buprenorphine
* Severe psychiatric illness or cognitively impairing ability to provide informed consent
* Current maternal incarceration
* Women who present for care \>31 0/7 weeks
* Multiple gestation pregnancy

Primary outcomes:
measure: Maternal drug use relapse
timeFrame: up to 12 months post-delivery
Secondary outcomes:
measure: Naltrexone side effects or adverse events
timeFrame: up to 12 months post-delivery
measure: Fetal heart rate monitoring from NST
timeFrame: 27- 41 weeks gestation
measure: Biophysical profile score calculated from NST
timeFrame: 27 - 41 weeks gestation
measure: Maternal hair cortisol levels
timeFrame: Birth and 4 weeks post-delivery
measure: Infant hair cortisol levels
timeFrame: Birth and 4 weeks post-delivery
measure: Fetal growth based on ultrasound measurements
timeFrame: 18 - 41 weeks gestation
measure: Congenital fetal anomalies by ultrasound
timeFrame: 18 - 41 weeks gestation
measure: Congenital anomalies by physical examination
timeFrame: Birth
measure: Diagnosis of Neonatal Abstinence Syndrome (NAS)
timeFrame: From birth to 30 days
measure: Infant need for pharmacologic treatment
timeFrame: From birth to 30 days
measure: Infant need for adjunctive agent
timeFrame: From birth to 30 days
measure: Infant opioid replacement pharmacologic treatment
timeFrame: From birth to 30 days
measure: Infant birth hospitalization length of stay
timeFrame: From birth to 30 days
measure: Infant weight
timeFrame: Birth, 4 weeks, and 12 months
measure: Infant length
timeFrame: Birth, 4 weeks, and 12 months
measure: Infant head circumference
timeFrame: Birth, 4 weeks, and 12 months
measure: Infant neurobehavior-function assessed by the NNNS
timeFrame: 4 weeks of age
measure: Infant neurodevelopment assessed by Bayley III
timeFrame: 12 months of age
measure: Pharmacokinetic analysis of maternal naltrexone levels
timeFrame: 2nd trimester, 3rd trimester, delivery, 2-4 days after delivery, 4 weeks post-delivery
measure: Pharmacokinetic analysis of infant naltrexone levels
timeFrame: Delivery, 2-4 days after delivery, 4 weeks post-delivery
Other outcomes:
measure: Maternal DNA methylation profile
timeFrame: 36 weeks gestation
measure: Mu opioid receptor (OPRM1) gene single nucleotide (SNP) genotype
timeFrame: 36 weeks gestation
measure: Maternal saliva OPRM1 methylation status
timeFrame: Birth, 4 weeks postpartum
measure: Infant saliva OPRM1 methylation status
timeFrame: Birth, 4 weeks postpartum
measure: Breast milk naltrexone level
timeFrame: 4 weeks postpartum
measure: Retention in addiction treatment
timeFrame: up to 12 months post-delivery
measure: Maternal healthcare utilization
timeFrame: up to 12 months post-delivery
measure: Infant healthcare utilization
timeFrame: up to 12 months post-delivery
Locations:
city: Boston
country: United States
facility: Boston Medical Center
state: Massachusetts
city: Carrboro
country: United States
facility: University of North Carolina Chapel Hill
state: North Carolina
Study officials:
affiliation: Boston Medical Center
name: Elisha Wachman, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Jones HE, Chisolm MS, Jansson LM, Terplan M. Naltrexone in the treatment of opioid-dependent pregnant women: the case for a considered and measured approach to research. Addiction. 2013 Feb;108(2):233-47. doi: 10.1111/j.1360-0443.2012.03811.x. Epub 2012 Apr 4.
citation: Saia KA, Schiff D, Wachman EM, Mehta P, Vilkins A, Sia M, Price J, Samura T, DeAngelis J, Jackson CV, Emmer SF, Shaw D, Bagley S. Caring for Pregnant Women with Opioid Use Disorder in the USA: Expanding and Improving Treatment. Curr Obstet Gynecol Rep. 2016;5(3):257-263. doi: 10.1007/s13669-016-0168-9. Epub 2016 Jul 1.
citation: Wachman EM, Saia K, Miller M, Valle E, Shrestha H, Carter G, Werler M, Jones H. Naltrexone Treatment for Pregnant Women With Opioid Use Disorder Compared With Matched Buprenorphine Control Subjects. Clin Ther. 2019 Sep;41(9):1681-1689. doi: 10.1016/j.clinthera.2019.07.003. Epub 2019 Jul 27.