Medication Treatment for Opioid Use Disorder in Expectant Mothers (MOMs)

Medication Treatment for Opioid Use Disorder in Expectant Mothers (MOMs): a Pragmatic Randomized Trial Comparing Extended-release and Daily Buprenorphine Formulations

The primary objective of this study is to evaluate the impact of treating opioid use disorder (OUD) in pregnant women with extended-release buprenorphine (BUP-XR), compared to sublingual buprenorphine (BUP-SL), on mother and infant outcomes. The primary hypothesis is that the BUP-XR group will not have greater illicit opioid use than the BUP-SL group during pregnancy (non-inferiority).

Study Overview

• Status: Completed
• Conditions: Pregnancy Related; Opioid-Related Disorders; Substance Abuse; Drug Abuse; Drug Addiction; Neonatal Abstinence Syndrome; Drug Abuse in Pregnancy; Neonatal Opioid Withdrawal Syndrome
• Intervention / Treatment: Drug: Buprenorphine Injection; Drug: Buprenorphine Sublingual Product

Detailed Description

This is an intent-to-treat, two-arm, open-label, pragmatic randomized controlled trial. Eligible participants will be randomized in a 1:1 ratio to BUP-XR or BUP-SL, balancing on site, estimated gestational age (EGA) at time of randomization (6 weeks-18 weeks vs. 19 weeks-30 weeks), and whether they are on BUP-SL at the time of randomization (yes vs. no). Participants will be provided with study medication and attend weekly medication visits through 12 months postpartum.

• Study Type: Interventional
• Enrollment (Actual): 140
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Florida
    • Jacksonville, Florida, United States, 32204
      • Gateway Community Services
  • Massachusetts
    • Boston, Massachusetts, United States, 02118
      • Boston Medical Center
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital HOPE Clinic
  • New Mexico
    • Albuquerque, New Mexico, United States, 87106
      • University of New Mexico Milagro Clinic
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • University of Cincinnati Health Perinatal Addictions Program
  • Oregon
    • Portland, Oregon, United States, 97214
      • CODA, Inc.
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • Pregnancy Recovery Center at Magee-Womens Hospital of UPMC
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center
  • Utah
    • Salt Lake City, Utah, United States, 84108
      • University of Utah SUPeRAD Clinic
  • Washington
    • Seattle, Washington, United States, 98107
      • Addiction Recovery Services (ARS), Swedish Medical Center
  • West Virginia
    • Huntington, West Virginia, United States, 25701
      • Marshall Health MARC Program

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 37 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Potential participants must:

1. be 18-41 years of age
2. be pregnant with an estimated gestational age (EGA) of 6 - 30 weeks at randomization, has evidence of a viable intrauterine pregnancy if EGA < 12 weeks and is not planning to terminate the pregnancy
3. have a single fetus pregnancy (can be based on self-report if an objective assessment is unavailable)
4. meet Diagnostic and Statistical Manual (DSM)-5 criteria for moderate/severe OUD and be a good candidate for BUP maintenance and/or be currently prescribed BUP for the treatment of OUD
5. be willing to be randomized to BUP-XR or BUP-SL and to comply with study procedures, including weekly Medication Check Visits
6. be planning to deliver at one of the hospitals for which the BORN survey was completed and that: a) has a written protocol for the management of neonatal abstinence syndrome (NAS) / neonatal withdrawal syndrome (NOWS), b) offers rooming-in while infants are being observed for NAS/NOWS; and c) does not send infants home on opioids for the treatment of NAS/NOWS
7. be enrolled in outpatient addiction treatment at a participating site (e.g., have completed intake)
8. be able to understand the study, and having understood, provide written informed consent in English

Exclusion Criteria:

Potential participants must not:

1. have a physiological dependence on alcohol or sedatives requiring medical detoxification

2. have a psychiatric condition that, in the judgment of the site medical clinician (MC), would make study participation unsafe or which would make treatment compliance difficult. Examples include:

   • Suicidal or homicidal ideation requiring immediate attention
   • Severe, inadequately-treated mental health disorder (e.g., active psychosis, uncontrolled bipolar disorder)

3. have a medical condition that, in the judgment of the study MC, would make study participation unsafe or which would make treatment compliance difficult. Medical conditions that may compromise participant safety or study conduct include, but are not limited to, allergy/sensitivity to study medications and the following based on clinical labs:

   • aspartate aminotransferase (AST) / alanine aminotransferase (ALT) greater than 5X upper limit of normal
   • serum creatinine greater than 1.5X upper limit of normal
   • total bilirubin greater than 1.5X upper limit of normal
4. be currently in jail, prison or any inpatient overnight facility as required by court of law or have pending legal action or other situation (e.g., unstable living arrangements) that, in the judgement of the site investigator, could prevent participation in the study or in any study activities;
5. be currently receiving methadone or naltrexone for the treatment of OUD;
6. be enrolled in or planning to enroll in treatment beyond the level 3.3 (Clinically Managed Population-Specific High-Intensity Residential Services) of the American Society of Addiction Medicine criteria; for level 3.3, the participant must have the ability to leave the facility unaccompanied by staff as needed;
7. be enrolled in or planning to enroll in: a) a trial testing medication for managing OUD during pregnancy; b) research testing an intervention for substance use disorder or NOWS in their infant unless they are willing to provide a release for the research records.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BUP-XR; Weekly subcutaneous Buprenorphine Injection (CAM2038) during pregnancy. During the 12-month postpartum phase, participants who are breastfeeding will continue receiving subcutaneous Buprenorphine Injection weekly; participants who are not breastfeeding will receive subcutaneous Buprenorphine Injection monthly. The target doses will be 24 mg for the weekly formulation and 96 mg for the monthly formulation, but the actual dose may be lower or higher as determined by the prescribing clinician (e.g., based on craving/withdrawal experienced by the participant, etc.).	Drug: Buprenorphine Injection; Weekly and monthly formulations of injectable, extended-release buprenorphine (BUP-XR).; Other Names: CAM2038
Active Comparator: BUP-SL; Daily sublingual buprenorphine, with or without naloxone, based on site preference, during pregnancy and during the 12-month postpartum phase. The target dose will be 16 mg daily, but the actual dose may be lower or higher as determined by the prescribing clinician (e.g., based on craving/withdrawal experienced by the participant, etc.).	Drug: Buprenorphine Sublingual Product; Sublingual buprenorphine (BUP-SL), administered daily.; Other Names: Subutex; Suboxone

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Illicit Opioid-negative Urine Samples During Pregnancy	Weekly urine samples are shipped to a central laboratory, where they are analyzed for presence of illicit opioids and/or their metabolites. Participants were randomized when they were 6-30 weeks estimated gestational age and, thus, the number of scheduled assessments varied between participants.	From screening (at 6-30 weeks estimated gestational age) to delivery, an average of 10-34 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Opioid Medication for Neonatal Opioid Withdrawal Syndrome (NOWS) Symptoms	Use of opioid medication for NOWS symptoms will be abstracted from the medical record.	Neonate discharge from hospital, typically within 1 month postpartum
Percentage of Illicit Opioid-negative Urine Samples Postpartum	Weekly urine samples are shipped to a central laboratory, where they are analyzed for presence of illicit opioids and/or their metabolites.	Delivery through 12 months postpartum
Percentage of Days With Study Medication Adherence During Pregnancy	Adherence to treatment from screening to delivery, checked weekly. Participants were randomized when they were 6-30 weeks estimated gestational age and, thus, the number of scheduled assessments varied between participants.	From screening (at 6-30 weeks estimated gestational age) to delivery, an average of 10-34 weeks
Percentage of Days With Study Medication Adherence - Postpartum	Adherence to treatment from delivery through 12 months postpartum, checked weekly.	Delivery through 12 months postpartum
Percentage of Drug and Alcohol-negative Urine Samples During Pregnancy	Weekly urine samples are shipped to a central laboratory, where they are analyzed for presence of alcohol, illicit drugs and/or their metabolites. Participants were randomized when they were 6-30 weeks estimated gestational age and, thus, the number of scheduled assessments varied between participants.	From screening (at 6-30 weeks estimated gestational age) to delivery, an average of 10-34 weeks
Percentage of Drug and Alcohol-negative Urine Samples - Postpartum Phase	Weekly urine samples are shipped to a central laboratory, where they are analyzed for presence of alcohol, illicit drugs and/or their metabolites, excluding cotinine.	Delivery through 12 months postpartum
Opioid Craving Scale - Pregnancy	The scale consists of 3 items, measuring craving, cue-induced craving, and likelihood of using, rated on a visual analogue scale from 0-10. The total is calculated by averaging the 3 item scores. Higher scores indicate greater levels of opioid craving. Participants were randomized when they were 6-30 weeks estimated gestational age and, thus, the number of scheduled assessments varied between participants. The measure was assessed at randomization (6-30 weeks estimated gestational age), two weeks post randomization and then monthly until delivery, average score reported.	Assessed at randomization (6-30 weeks estimated gestational age), two weeks post randomization and then monthly until delivery
Opioid Craving Scale - Postpartum	The scale measures craving, cue-induced craving, and likelihood of using, rated on a visual analogue scale from 0-10. The total is calculated by averaging the 3 item scores. Higher scores indicate greater levels of opioid craving. The measure was assessed at months 1, 3, 6, 9, and 12 post-delivery, average score reported	Assessed at months 1, 3, 6, 9, and 12 post-delivery
Adequacy of Prenatal Care Utilization Index	The information was derived from either medical records or the birth certificate. Information was not obtained for 74 participants.	At delivery
Short Opiate Withdrawal Scale (SOWS)-Gossop - Pregnancy	Measure of maternal opioid withdrawal symptoms. The Short Opiate Withdrawal Scale-Gossop has scores rated on a scale of 0 (none) to 3 (severe) per question. The total score of the SOWS-Gossop ranges from 0-30. Participants were randomized when they were 6-30 weeks estimated gestational age and, thus, the number of scheduled assessments varied between participants. The measure was assessed at randomization (6-30 weeks estimated gestational age), two weeks post randomization and then monthly until delivery, average score reported.	Assessed at randomization (6-30 weeks estimated gestational age), two weeks post randomization and then monthly until delivery
Short Opiate Withdrawal Scale (SOWS)-Gossop - Postpartum	Measure of maternal opioid withdrawal symptoms. The Short Opiate Withdrawal Scale-Gossop has scores rated on a scale of 0 (none) to 3 (severe) per question. The total score of the SOWS-Gossop ranges from 0-30. The measure was assessed at months 1, 3, 6, 9, and 12 post-delivery, average score reported.	Assessed at months 1, 3, 6, 9, and 12 post-delivery
Total Days of Neonatal Opioid Treatment During the Hospital Stay	Number of days of NOWS treatment for those infants that did receive it, abstracted from the medical record.	Neonate discharge from hospital, typically within 1 month postpartum
Infant Hospital Length of Stay	Infant hospital length of stay (LOS) defined as the infant's age, in days, at discharge will be abstracted from the medical record. (all infants)	Neonate discharge from hospital, typically within 1 month postpartum
Neonatal Opioid Withdrawal Syndrome (NOWS) Peak Score	NOWS peak score will be abstracted from the medical record. The scale used is the Finnegan-modified; the score ranges from 0-46, a score of 8 or higher indicates withdrawal.	Neonate discharge from hospital, typically within 1 month postpartum
Custody at Discharge	For example, whether the infant is discharged in custody of mother, other relative, foster/adoptive family, etc. This will be abstracted from the medical record. Maternal custody - number & percentage.	Neonate discharge from hospital, typically within 1 month postpartum
Child Protective Services Open Case	Whether or not there is an open child protective services at discharge (yes/no) will be abstracted from the medical record. Percentage of cases open with child protective services.	Neonate discharge from hospital, typically within 1 month postpartum
Ages and Stages Questionnaire, Third Edition (ASQ-3)	To screen for developmental issues in the infant. Developmental issues at 12 months - percentage. Developmental issues assessed with The Ages and Stages Questionnaire, third edition scores each item as Yes (10 points), Sometimes (5 points), or Not Yet (0 points), with total scores compared to cutoffs to identify delays.	12 months postpartum

Collaborators and Investigators

• Sponsor: T. John Winhusen, PhD
• Collaborators: National Institute on Drug Abuse (NIDA); The Emmes Company, LLC
• Investigators: Principal Investigator: T. John Winhusen, PhD, University of Cincinnati

Publications and helpful links

General Publications

• Kropp FB, Smid MC, Lofwall MR, Wachman EM, Martin PR, Murphy SM, Wilder CM, Winhusen TJ. Collaborative care programs for pregnant and postpartum individuals with opioid use disorder: Organizational characteristics of sites participating in the NIDA CTN0080 MOMs study. J Subst Use Addict Treat. 2023 Jun;149:209030. doi: 10.1016/j.josat.2023.209030. Epub 2023 Apr 4.
• Winhusen TJ, Lofwall MR, Kropp F, Lewis D, Smid MC, Young JL, Hodgkins C, Krans EE, Hansen Z, Wachman EM, Schiff DM, Guille C, Rudolf V, Chowdhury T, Leeman L, Lewis M, Matthews AG, Cochran G, King J, Wilder C, Rosa C. Extended-Release vs Sublingual Buprenorphine in Pregnancy Through 12 Months Post Partum: A Randomized Clinical Trial. JAMA Intern Med. 2026 May 1;186(5):533-543. doi: 10.1001/jamainternmed.2026.0057.
• Krans EE, Lewis D, Douaihy A, Lofwall MR, Kropp F, Martin PR, Sanghani RS, Cottrell JN, Winhusen TJ. Cigarette use and smoking cessation goals among pregnant women with opioid use disorder. J Subst Use Addict Treat. 2025 Dec 20:209865. doi: 10.1016/j.josat.2025.209865. Online ahead of print.
• Cash E, Cochran G, Smid MC, Charles JE, Humiston G, Wei Y, Mauerman N, Carlston K, Broussard G, Sengpraseut B, Martin PR, Winhusen TJ. Overdose risk profiles in pregnancy: Latent class analysis of pregnant individuals with opioid use disorder. J Subst Use Addict Treat. 2025 Sep 25:209809. doi: 10.1016/j.josat.2025.209809. Online ahead of print.
• Snyder AM, Math S, Campbell K, Schiff DM, Wheeler A, Carlston K, Gordon AJ, Winhusen TJ, Cochran G, Smid MC. Protocol Commentary for the SUCCESS (Successful Recruitment and Retention in a Randomized Controlled Trial of Pregnant Participants with Opioid Use Disorder) Study. Subst Use Addctn J. 2025 Oct;46(4):1040-1046. doi: 10.1177/29767342251334490. Epub 2025 Jul 11.
• Winhusen TJ, Kropp F, Greenfield SF, Krans EE, Lewis D, Martin PR, Gordon AJ, Davies TH, Wachman EM, Douaihy A, Parker K, Xin X, Jalali A, Lofwall MR. Trauma Prevalence and Its Association With Health-related Quality of Life in Pregnant Persons With Opioid Use Disorder. J Addict Med. 2025 Jan-Feb 01;19(1):20-25. doi: 10.1097/ADM.0000000000001366. Epub 2024 Aug 6.

Study record dates

Study Major Dates

• Study Start (Actual): July 21, 2020
• Primary Completion (Actual): January 31, 2025
• Study Completion (Actual): January 31, 2025

Study Registration Dates

• First Submitted: April 9, 2019
• First Submitted That Met QC Criteria: April 16, 2019
• First Posted (Actual): April 18, 2019

Study Record Updates

• Last Update Posted (Actual): June 4, 2026
• Last Update Submitted That Met QC Criteria: May 8, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: CTN-0080; clinical trials network; medication assisted treatment
• Additional Relevant MeSH Terms: Narcotic-Related Disorders; Mental Disorders; Infant, Newborn, Diseases; Chemically-Induced Disorders; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Opioid-Related Disorders; Substance-Related Disorders; Neonatal Abstinence Syndrome; Heterocyclic Compounds; Heterocyclic Compounds, Fused-Ring; Pharmaceutical Preparations; Alkaloids; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds; Heterocyclic Compounds, 4 or More Rings; Drug Combinations; Naloxone; Morphinans; Opiate Alkaloids; Heterocyclic Compounds, Bridged-Ring; Phenanthrenes; Buprenorphine, Naloxone Drug Combination; Buprenorphine
• Other Study ID Numbers: 2019-0429-1; UG1DA013732 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Data will be transmitted by the study Data and Statistics Center to the designated party for de-identification, posting, storing, and archiving on NIDA's Data Share website. Data Share is an online repository of data from studies funded by the National Institute on Drug Abuse. All de-identified individual participant data is expected to be made available.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No