MOM NEST Study: Maternal Opioid Medication: Naltrexone Efficacy Study

NCT ID: NCT03718104

Last Updated: 2024-11-04

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

46 participants

Study Classification

OBSERVATIONAL

Study Start Date

2018-12-01

Study Completion Date

2024-05-08

Brief Summary

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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

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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.

Conditions

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

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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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.

Pharmacokinetic analysis

Intervention Type 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.

Safety and Efficacy

Intervention Type 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).

Genetic and epigenetic analysis

Intervention Type 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.

Breast milk analysis

Intervention Type 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.

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.

Safety and Efficacy

Intervention Type 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).

Genetic and epigenetic analysis

Intervention Type 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.

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.

Pharmacokinetic analysis

Intervention Type 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.

Genetic and epigenetic analysis

Intervention Type 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.

Breast milk analysis

Intervention Type 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.

Interventions

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Pharmacokinetic analysis

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.

Intervention Type OTHER

Safety and Efficacy

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).

Intervention Type OTHER

Genetic and epigenetic analysis

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.

Intervention Type GENETIC

Breast milk analysis

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.

Intervention Type OTHER

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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University of North Carolina

OTHER

Sponsor Role collaborator

University of California, San Diego

OTHER

Sponsor Role collaborator

Boston University

OTHER

Sponsor Role collaborator

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

NIH

Sponsor Role collaborator

Boston Medical Center

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Elisha Wachman, MD

Role: PRINCIPAL_INVESTIGATOR

Boston Medical Center

Locations

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Boston Medical Center

Boston, Massachusetts, United States

Site Status

University of North Carolina Chapel Hill

Carrboro, North Carolina, United States

Site Status

Countries

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United States

References

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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.

Reference Type BACKGROUND
PMID: 22471668 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 27563497 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 31358302 (View on PubMed)

Other Identifiers

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R01HD096798-01

Identifier Type: NIH

Identifier Source: secondary_id

View Link

H-37773

Identifier Type: -

Identifier Source: org_study_id

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