Medication Treatment for Opioid Use Disorder in Expectant Mothers: Conceptual Model Assessments Sub-study

Study Overview
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Brief Summary
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This is a sub-study of NIDA CTN Protocol 0080: Medication Treatment for Opioid Use Disorder in Expectant Mothers (MOMs; Unique protocol ID: 2019-0429-1). Participants in MOMs will be offered the opportunity to enroll in this sub-study, which is designed to evaluate conceptual models of the mechanisms by which extended-release buprenorphine (BUP-XR), may improve mother-infant outcomes, compared to sublingual buprenorphine (BUP-SL). The additional data collected in this sub-study will be combined with data from the main MOMs trial. It is hypothesized that: (1) the buprenorphine blood levels will vary, depending on which formulation of buprenorphine was received, (2) the variation in buprenorphine blood levels will be associated with fetal behavior (including fetal heart rate variability) (3) the variation in buprenorphine blood levels will be associated with differences in mother outcomes (including medication adherence and illicit opioid use) (4) the variation in buprenorphine blood levels and in fetal behavior will be associated with infant outcomes (including neonatal opioid withdrawal syndrome and infant development).

Official Title
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NIDA CTN Protocol 0080: Medication Treatment for Opioid Use Disorder in Expectant Mothers (MOMs): a Pragmatic Randomized Trial Comparing Extended-release and Daily Buprenorphine Formulations: Conceptual Model Assessments (CMA) Sub-study

Conditions
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Opioid-Related Disorders, Drug Addiction, Pregnancy Related, Substance Abuse, Drug Abuse, Neonatal Abstinence Syndrome, Neonatal Opioid Withdrawal Syndrome, Drug Abuse in Pregnancy

Intervention / Treatment
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* Drug: Buprenorphine Injection
* Drug: Buprenorphine Sublingual Product


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participating in the MOMs trial (Unique protocol ID: 2019-0429-1) Exclusion Criteria: -

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 41 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BUP-XR<br>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<br>* Weekly and monthly formulations of injectable, extended-release buprenorphine (BUP-XR).<br>* Other names: CAM2038;|
| Active Comparator: BUP-SL<br>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<br>* Sublingual buprenorphine (BUP-SL), administered daily.<br>* Other names: Suboxone;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmin of buprenorphine and metabolites in plasma | A blood draw at the estimated time of minimum drug concentration (trough) to evaluate adequacy of dose for the conceptual model. | 2 weeks post-randomization | 
| Cmin of buprenorphine and metabolites in plasma | A blood draw at the estimated time of minimum drug concentration (trough) to evaluate adequacy of dose for the conceptual model. | 4 weeks post-randomization | 
| Fetal heart rate variability | This is the measure of primary interest from the fetal evaluation (non-stress test and biophysical profile). | Estimated gestational age (EGA) approximately 36 weeks | 
| Cmin of buprenorphine and metabolites in plasma | A blood draw at the estimated time of minimum drug concentration (trough) to evaluate trough-to-peak fluctuation for the conceptual model. | Estimated gestational age (EGA) approximately 36 weeks | 
| Cmax of buprenorphine and metabolites in plasma | A blood draw at the estimated time of maximum drug concentration (peak) to evaluate trough-to-peak fluctuation for the conceptual model. | Estimated gestational age (EGA) approximately 36 weeks | 
| Concentration of buprenorphine and metabolites in maternal plasma | A blood draw around the time of delivery to evaluate the association between drug concentration and neonatal opioid withdrawal syndrome outcomes. | Delivery | 
| Concentration of buprenorphine and metabolites in cord plasma | Cord blood will be collected and used to estimate fetal exposure to buprenorphine. | Delivery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CTN-0080, clinical trials network, medication assisted treatment, pharmacokinetics