MOM NEST Study: Maternal Opioid Medication: Naltrexone Efficacy Study

NCT03718104 | Completed DMC

• 2 other identifiers: H-37773R01HD096798-01
• Study Type: observational
• Target: 46
• Locations: 1 country
• Sites: 2

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.

Conditions

Opioid-use Disorder; Neonatal Abstinence Syndrome; Pregnancy, High Risk; Alcohol Use Disorder

Keywords

naltrexone; buprenorphine/naloxone; maternal relapse; retention in care; pharmacokinetics; pharmacogenetics

Outcome Measures

Primary Outcomes (1)

• Maternal drug use relapse

  Maternal relapse of illicit and/or unprescribed drug use from maternal/provider report and or from urine toxicology testing at any point during the pregnancy and up to 12 months after delivery

  up to 12 months post-delivery

Secondary Outcomes (20)

• Naltrexone side effects or adverse events

  up to 12 months post-delivery

• Fetal heart rate monitoring from NST

  27- 41 weeks gestation

• Biophysical profile score calculated from NST

  27 - 41 weeks gestation

• Maternal hair cortisol levels

  Birth and 4 weeks post-delivery

• Infant hair cortisol levels

  Birth and 4 weeks post-delivery

Other Outcomes (8)

• Maternal DNA methylation profile

  36 weeks gestation

• Mu opioid receptor (OPRM1) gene single nucleotide (SNP) genotype

  36 weeks gestation

• Maternal saliva OPRM1 methylation status

  Birth, 4 weeks postpartum

Study Arms (3)

Naltrexone

Pregnant women with opioid use disorder on prescribed oral or extended-release naltrexone and their infants. Biospecimens collected from this group will undergo pharmacokinetic analysis, genetic and epigenetic analysis, and breast milk analysis. This group will also receive safety and efficacy interventions.

Other: Pharmacokinetic analysis; Other: Safety and Efficacy; Genetic: Genetic and epigenetic analysis; Other: Breast milk analysis

Buprenorphine/Naloxone

Pregnant women with opioid use disorder on prescribed buprenorphine/naloxone and their infants. Biospecimens collected from this group will undergo genetic and epigenetic analysis and the group will also receive safety and efficacy interventions.

Other: Safety and Efficacy; Genetic: Genetic and epigenetic analysis

Naltrexone - alcohol use disorder

Pregnant women with alcohol use disorder on prescribed naltrexone (oral or extended-release) and their infants. Biospecimens collected from this group will undergo pharmacokinetic analysis, genetic and epigenetic analysis, and breast milk analysis. This exploratory group will also receive safety and efficacy interventions.

Other: Pharmacokinetic analysis; Genetic: Genetic and epigenetic analysis; Other: Breast milk analysis

Interventions

Pharmacokinetic analysis OTHER

Pharmacokinetic analysis of maternal blood, maternal urine, cord blood, infant blood and urine for dyads in the naltrexone group at various time points in the pregnancy, at delivery, and 4 weeks postpartum.

Naltrexone; Naltrexone - alcohol use disorder

Safety and Efficacy OTHER

Examination of the safety and efficacy of naltrexone and comparison of outcomes with the buprenorphine/naloxone cohort. Outcomes examined will include: 1) maternal outcomes (relapse, retention in care, preterm labor); 2) fetal outcomes (growth, fetal anomalies, fetal distress, cortisol levels); and 3) infant outcomes (NAS, growth, neurodevelopment via NNNS exam at 4 weeks and Bayley exam at 12 months of age).

Buprenorphine/Naloxone; Naltrexone

Genetic and epigenetic analysis GENETIC

Maternal blood and saliva DNA samples will be genotyped for single nucleotide polymorphisms in the mu opioid receptor gene (OPRM1) to look for associations with effectiveness of NTX and BPH. In addition, DNA methylation levels in the OPRM1 promoter within maternal and infant saliva and placenta at delivery and 4 weeks postpartum will be examined. Lastly, we will compare genome-wide DNA methylation levels at delivery and 4 weeks postpartum in mother-infant dyads.

Buprenorphine/Naloxone; Naltrexone; Naltrexone - alcohol use disorder

Breast milk analysis OTHER

Mothers in the naltrexone group will have their breast milk analyzed at 4 weeks post-delivery for naltrexone levels, with corresponding maternal and infant plasma levels.

Naltrexone; Naltrexone - alcohol use disorder

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: Pregnant women
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Boston Medical Center: lead
• University of North Carolina: collaborator
• University of California, San Diego: collaborator
• Boston University: collaborator
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator

Study Sites (2)

Boston Medical Center

Boston, Massachusetts, 02118, United States

Location

University of North Carolina Chapel Hill

Carrboro, North Carolina, 27510, United States

Location

Related Publications (3)

• 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.

  PMID: 22471668 BACKGROUND

• 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.

  PMID: 27563497 BACKGROUND

• 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.

  PMID: 31358302 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

* Maternal and infant blood and urine samples for naltrexone pharmacokinetics * Cord blood for naltrexone pharmacokinetics * Breast milk for naltrexone levels * Maternal blood, saliva, and placental tissue for genotyping and DNA methylation * Maternal and infant samples for cortisol levels

MeSH Terms

Conditions

Opioid-Related Disorders; Neonatal Abstinence Syndrome; Alcoholism

Interventions

Safety

Condition Hierarchy (Ancestors)

Narcotic-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders; Infant, Newborn, Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Alcohol-Related Disorders

Intervention Hierarchy (Ancestors)

Accident Prevention; Accidents; Public Health; Environment and Public Health

Study Officials

• Elisha Wachman, MD

  Boston Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 19, 2018
• First Posted: October 24, 2018
• Study Start: December 1, 2018
• Primary Completion: May 8, 2024
• Study Completion: May 8, 2024
• Last Updated: November 4, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)