Treatment Model for Maternal Opioid Use Disorder and Infant Withdrawal

(SUPPORT Trial)

Recruiting at 2 trial locations

Overseen By Emma Farber, BA

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Pennsylvania

Must be taking: Buprenorphine

Disqualifiers: Severe psychopathology, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

50 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, it mentions that participants should have untreated opioid use disorder, which might imply that you should not be on medication-assisted treatment or buprenorphine when joining the study.

What data supports the effectiveness of this drug for maternal opioid use disorder and infant withdrawal?

Research shows that both buprenorphine and methadone are effective in treating opioid use disorder in pregnant women, with studies indicating positive outcomes for both the mothers and their infants. Buprenorphine, in particular, is associated with lower rates of neonatal abstinence syndrome (withdrawal symptoms in newborns) compared to methadone. ^{1 2 3 4 5}

Is the treatment safe for humans?

Research shows that both methadone and buprenorphine are generally safe for pregnant women with opioid use disorder and their babies. Studies have compared these treatments and found them to be safe for both mothers and newborns. ^{2 6 7 8 9}

How is the Implementation Model for Co-located MOUD Prescription unique for treating maternal opioid use disorder and infant withdrawal?

This treatment model is unique because it co-locates the prescription of medications like methadone and buprenorphine with other supportive therapies, making it easier for pregnant women to access comprehensive care in one place, which can improve outcomes for both mothers and infants. ^{2 10 11 12 13}

What is the purpose of this trial?

The purpose of this study is to address the gap in maternal OUD treatment and infant neonatal opioid withdrawal syndrome care. The research team will develop a treatment model and a set of strategies to provide evidence-based OUD treatment to postpartum mothers in NICUs. First, the investigators will conduct a needs assessment via in-depth qualitative interviews with NICU mothers and clinicians. Then, with the expertise of the advisory board, the the researchers will create a protocol for implementing maternal OUD treatment at the NICU bedside. The researchers will then implement the protocol in two partner NICUs and evaluate the acceptability and feasibility to patients, providers, and clinical, and administrative leaders. The goal of this research study is to integrate maternal mental health and substance abuse treatment in pediatric settings and to refine, test, and examine the acceptability and feasibility of applying the adapted model.

Research Team

Sara Kornfield, PhD

Principal Investigator

University of Pennsylvania

Eligibility Criteria

This trial is for postpartum mothers with Opioid Use Disorder (OUD) who have infants experiencing Neonatal Abstinence Syndrome (NAS) in the NICU. The study aims to help these mothers by providing treatment at their baby's bedside.

Inclusion Criteria

Mothers in Aim 1 should be diagnosed with opioid use disorder

Interview Participants in Aim 1 should be proficient in English language

Interview Participants in Aim 1 should be healthcare providers working within UPHS, who generally treat perinatal women or individuals with OUD (MD, DO, Advanced Practice Practitioner, Nurse, or Social Worker)

Exclusion Criteria

I do not have thoughts of harming myself or severe mental health issues.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Needs Assessment

Conduct in-depth qualitative interviews with NICU mothers and clinicians to assess needs and identify barriers and facilitators for OUD treatment.

Up to 9 months

Multiple interviews (in-person or virtual)

Protocol Development

Develop a protocol for implementing maternal OUD treatment at the NICU bedside with the advisory board.

Up to 9 months

Pilot Implementation

Implement and evaluate the adapted intervention in two partner NICUs to determine feasibility and acceptability.

Up to 1 year

Ongoing participation during NICU stay

Follow-up

Participants are monitored for safety and effectiveness after treatment, including retention in outpatient treatment.

Up to 1 year

Treatment Details

Interventions

• Implementation Model for Co-located MOUD Prescription

Trial Overview The trial is testing a new model where Medications for Opioid Use Disorder (MOUD) are prescribed right in the NICU. It involves assessing needs, creating protocols with experts, and evaluating how well this approach works in two NICUs.

Participant Groups

Group I: Case Series Experimental Treatment 1 Intervention

In Aim 3, all recruited participants will receive the intervention.

Implementation Model for Co-located MOUD Prescription is already approved in United States, European Union for the following indications:

Approved in United States as Methadone for:

• Opioid use disorder in pregnant women

Approved in United States as Buprenorphine for:

• Opioid use disorder in pregnant women

Approved in European Union as Methadone for:

• Opioid dependence

Approved in European Union as Buprenorphine for:

• Opioid dependence

Who Is Running the Clinical Trial?

University of Pennsylvania

Lead Sponsor

Trials

2,118

Recruited

45,270,000+

Findings from Research

In a study of 108 pregnant women and mothers with young children undergoing buprenorphine maintenance treatment for opioid use disorder, 73.2% retained treatment after 12 months, indicating a relatively high retention rate.

Patients with a history of psychiatric treatment or misdemeanor convictions were less likely to remain in treatment, suggesting that these factors may require more intensive support and tailored interventions to improve outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A retrospective analysis of treatment and retention outcomes of pregnant and/or parenting women with opioid use disorder. Lopian, KM., Chebolu, E., Kulak, JA., et al.[2020]

Buprenorphine shows better or similar safety outcomes compared to methadone for treating neonatal abstinence syndrome (NAS), with fewer infants requiring treatment and shorter hospital stays, based on a review of 5 critical studies.

Both medications are effective for pregnant women with opioid dependence, but buprenorphine may be a preferable option due to its improved outcomes, although more extensive studies are needed to confirm its safety and advantages.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Buprenorphine Versus Methadone for Opioid Dependence in Pregnancy. Noormohammadi, A., Forinash, A., Yancey, A., et al.[2018]

In a study of 62 mother-neonate pairs, neonates born to mothers treated with buprenorphine and naloxone had a significantly lower prevalence of neonatal abstinence syndrome (25.1%) compared to those born to mothers treated with methadone (51.6%).

Neonates exposed to buprenorphine and naloxone also experienced lower peak neonatal abstinence syndrome scores and shorter hospital stays, indicating a potentially safer and more effective treatment option during pregnancy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Buprenorphine and naloxone compared with methadone treatment in pregnancy. Wiegand, SL., Stringer, EM., Stuebe, AM., et al.[2022]

Women with opioid use disorder (OUD) who were on opioid maintenance therapy (OMT) were more likely to continue treatment and maintain custody of their children, highlighting the effectiveness of OMT in supporting recovery.

In contrast, women enrolled in residential treatment programs during pregnancy were less likely to continue treatment or keep custody, suggesting that the type of treatment setting can significantly impact outcomes for mothers with OUD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Continuation in Treatment and Maintenance of Custody of Newborns After Delivery in Women With Opioid Use Disorder. Schauberger, CW., Borgert, AJ., Bearwald, B.[2021]

In a study of 89 infants born to mothers on buprenorphine, 43.8% required morphine treatment for neonatal abstinence syndrome (NAS), with an average of 15.9 days on morphine and a 20-day hospital stay.

The study found that higher doses of buprenorphine did not increase the severity of NAS, and exclusive breastfeeding significantly reduced the likelihood of needing morphine treatment, indicating it is a safe and beneficial practice for these infants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Does Maternal Buprenorphine Dose Affect Severity or Incidence of Neonatal Abstinence Syndrome? Wong, J., Saver, B., Scanlan, JM., et al.[2019]

Buprenorphine treatment for pregnant women with opioid use disorder is associated with a lower risk of preterm birth and results in greater birth weight and larger head circumference compared to methadone, based on a review of 18 studies involving 2,146 participants.

There were no significant differences in rates of fetal death or congenital anomalies between the two treatments, suggesting that buprenorphine does not pose greater risks than methadone for these outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Buprenorphine compared with methadone to treat pregnant women with opioid use disorder: a systematic review and meta-analysis of safety in the mother, fetus and child. Zedler, BK., Mann, AL., Kim, MM., et al.[2023]

Infants exposed to buprenorphine alone had a significantly higher rate of neonatal abstinence syndrome (54.6%) compared to those exposed to the buprenorphine and naloxone combination (35.3%), suggesting that the combination product may be safer for fetal outcomes.

The study indicates that while the combined buprenorphine and naloxone product is associated with lower odds of neonatal abstinence syndrome, these results were not statistically significant after adjusting for other factors, indicating that both treatments are acceptable options for managing opioid use disorder during pregnancy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Buprenorphine and Naloxone Versus Buprenorphine for Opioid Use Disorder in Pregnancy: A Cohort Study. Mullins, N., Galvin, SL., Ramage, M., et al.[2021]

In a study of 609 opioid-dependent pregnant women, those treated with buprenorphine had better outcomes, including starting treatment earlier, longer gestation periods, and larger infants compared to those treated with methadone.

Newborns from mothers on buprenorphine required significantly less treatment for neonatal abstinence syndrome and for shorter durations, suggesting that buprenorphine may be a safer and more effective option for treating opioid dependence during pregnancy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Methadone and buprenorphine for opioid dependence during pregnancy: a retrospective cohort study. Meyer, MC., Johnston, AM., Crocker, AM., et al.[2022]

Infants born to mothers treated with buprenorphine/naloxone during pregnancy experienced neonatal abstinence syndrome less frequently (64%) compared to those born to mothers treated with methadone (80%), suggesting a potential safety advantage for buprenorphine/naloxone.

Both treatment groups showed similar neonatal outcomes in terms of gestational age, birth weight, and need for neonatal intensive care, indicating that neither medication led to significant adverse effects on newborns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neonatal outcomes following in utero exposure to buprenorphine/naloxone or methadone. Gawronski, KM., Prasad, MR., Backes, CR., et al.[2022]

Maternal opioid use disorder (OUD) is increasingly common due to the opioid epidemic, and effective management typically includes opioid agonist treatments like methadone or buprenorphine, along with therapy and counseling.

Neonatal opioid withdrawal syndrome can occur in newborns of mothers with OUD, impacting their neurobehavioral functioning, and effective treatment relies heavily on nonpharmacologic comforting measures that require maternal involvement.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk Factors Associated with Perinatal Relapse to Opioid Use Disorder. Nawaz, N., Hester, M., Oji-Mmuo, CN., et al.[2022]

In a study of 588 mother-neonate pairs, neonates born to mothers treated with buprenorphine/naloxone had a significantly lower prevalence of neonatal opioid withdrawal syndrome (NOWS) compared to those treated with methadone, with 38.7% versus 65.8% requiring treatment.

Buprenorphine/naloxone treatment was associated with a reduced need for multiple medications for NOWS and lower rates of fetal growth restriction, suggesting it may be a safer option for treating opioid use disorder during pregnancy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of neonatal outcomes in pregnant women undergoing medication-assisted treatment of opioid use disorder with methadone or buprenorphine/naloxone. Petrich, M., Battin, M., Walker, E., et al.[2023]

A study of 32 pregnant women undergoing buprenorphine treatment for opioid dependence revealed medium risk of abuse in their parenting skills, indicating potential issues like inappropriate expectations and low empathy towards their children.

Despite showing deficits in parenting skills, these women did not express significant concerns about their ability to parent, highlighting the need for targeted educational interventions to improve their parenting knowledge and address concerns about neonatal abstinence syndrome (NAS).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Parenting and concerns of pregnant women in buprenorphine treatment. Rizzo, RA., Neumann, AM., King, SO., et al.[2021]

In Illinois, a total of 89 treatment resources for opioid use disorder (OUD) in pregnant women were identified, but these resources were concentrated in only 36% of the counties, highlighting significant geographic disparities.

Counties with limited OUD treatment resources had higher rates of neonatal abstinence syndrome (NAS), with 66% of NAS cases in rural areas occurring in counties lacking any OUD treatment options, indicating a critical need for improved access to medication-assisted treatment (MAT) in these regions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The interaction of neonatal abstinence syndrome and opioid use disorder treatment availability for women insured by medicaid. Reising, VA., Horne, A., Bennett, AC.[2021]

References

1. United States pubmed.ncbi.nlm.nih.gov

A retrospective analysis of treatment and retention outcomes of pregnant and/or parenting women with opioid use disorder. [2020]

2. United States pubmed.ncbi.nlm.nih.gov

Buprenorphine Versus Methadone for Opioid Dependence in Pregnancy. [2018]

3. United States pubmed.ncbi.nlm.nih.gov

Buprenorphine and naloxone compared with methadone treatment in pregnancy. [2022]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Continuation in Treatment and Maintenance of Custody of Newborns After Delivery in Women With Opioid Use Disorder. [2021]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Does Maternal Buprenorphine Dose Affect Severity or Incidence of Neonatal Abstinence Syndrome? [2019]

6. England pubmed.ncbi.nlm.nih.gov

Buprenorphine compared with methadone to treat pregnant women with opioid use disorder: a systematic review and meta-analysis of safety in the mother, fetus and child. [2023]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Buprenorphine and Naloxone Versus Buprenorphine for Opioid Use Disorder in Pregnancy: A Cohort Study. [2021]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Methadone and buprenorphine for opioid dependence during pregnancy: a retrospective cohort study. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Neonatal outcomes following in utero exposure to buprenorphine/naloxone or methadone. [2022]

10. United States pubmed.ncbi.nlm.nih.gov

Risk Factors Associated with Perinatal Relapse to Opioid Use Disorder. [2022]

11. England pubmed.ncbi.nlm.nih.gov

Comparison of neonatal outcomes in pregnant women undergoing medication-assisted treatment of opioid use disorder with methadone or buprenorphine/naloxone. [2023]

12. United States pubmed.ncbi.nlm.nih.gov

Parenting and concerns of pregnant women in buprenorphine treatment. [2021]

13. United States pubmed.ncbi.nlm.nih.gov

The interaction of neonatal abstinence syndrome and opioid use disorder treatment availability for women insured by medicaid. [2021]