Pharmacologically-based Strategies for Opioid Substitution Therapy During Pregnancy

Phase 2

Terminated

• Conditions: Pregnancy; Opiate Addiction
• Interventions: Drug: Frequency Group; Drug: Magnitude Group

• Registration Number: NCT03831113
• Lead Sponsor: Steve N. Caritis, MD

Brief Summary

This study is a pharmacodynamic study in pregnant women evaluating the relationship between buprenorphine concentration and outcome such as opioid withdrawal symptoms , NAS scores, neurodevelopmental and neuroanatomic outcomes. Strategies to reduce opioid exposure will be explored. There are 4 specific aims but only specific aim 4 is a clinical trial and reported here. In specific aim 4, eligible consenting women on buprenorphine in an MAT clinic will be assigned to 2 dose reduction regimens and their response to dose reduction will be measured using a visual analog scale.

Detailed Description

Opioid use has reached a staggering level and the associated deaths, neonatal consequences and economic impact are devastating. Buprenorphine and methadone are the two most commonly used medications for pregnant women in a Medication Assisted Treatment (MAT) program. Yet, the target concentration of these agents is not clearly identified. Furthermore, the relationship between drug exposure and adverse effects such as Neonatal Abstinence Syndrome and neurodevelopmental outcomes is unclear but contemporary thinking is that exposure (defined by maternal dose) is unrelated to adverse outcomes. The benefit of an MAT strategy is based on strong clinical data that demonstrates an improvement in perinatal outcomes in women participating in an MAT program. However, some women prefer to stop opioid medications entirely , but are not afforded this option in many MAT programs. The possibility that MAT is associated with some harms has received little attention but there are data that suggest that opioids adversely affect the fetal brain. If MAT is indeed associated with potential harms, then the option of Medically Supervised Withdrawal could be considered.

This study will assess two dose reduction strategies in a cohort of women who desire a reduction or elimination of their opioid exposure. The magnitude group will reduce the dose by either 1 or 2 mg weekly. The frequency group will reduce their dose by 2 mg alternately in one or 2 weeks

Study Timeline

• Study First Submitted: 2019-01-22
• Study First Submitted QC: 2019-02-04
• Study First Posted: 2019-02-05
• Study Start: 2019-04-13
• Primary Completion: 2022-12-22
• Study Completion: 2022-12-22
• Results First Submitted: 2024-07-30
• Status Verified: 2024-08
• Results First Submitted QC: 2024-08-23
• Last Update Submitted: 2024-08-23
• Results First Posted: 2024-08-29
• Last Update Posted: 2024-08-29

Recruitment & Eligibility

• Status: TERMINATED
• Sex: Female
• Target Recruitment: 13

Inclusion Criteria

1. On a stable dosing regimen of BUP for at least 2 weeks as part of an established medication- assisted treatment (MAT) program.
2. Willingness to undergo supervised dose reduction
3. Subject willingness to be assigned to either the Magnitude, or Frequency group.
4. Single gestation between 14-30 weeks at the initiation of the dose reduction
5. On a BUP dose between 6- 24 mg daily (lower doses will not provide sufficient data points)
6. Willingness to have urine samples tested for drugs of abuse and blood samples tested for BUP+M concentrations during the Medical Supervised Withdrawal (MSW) clinic appointments
7. Willingness to attend weekly or biweekly MSW clinic appointments and to have daily contact via text messaging and to complete daily logs of sleep quality, withdrawal symptoms and symptoms of craving.
8. Willingness to attend psychosocial support meetings as needed.

Exclusion Criteria

1. Current use of cocaine, heroin, benzodiazepines, barbiturates, phencyclidine (PCP), or opioids other than BUP.
2. Currently taking more than two mental health medications
3. Active moderately severe depression (PHQ-9 score ≥15 or suicidal ideation)
4. Current incarceration
5. Lack of a phone or transportation to and from clinic
6. Major fetal malformation
7. Mother with significant vaginal bleeding or serious medical or obstetrical complication that could adversely affect the study
8. Planned delivery at another institution
9. HIV or AIDS
10. Diagnosis of schizoaffective disorder or psychosis

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Frequency Group	Frequency Group	Subjects will receive dose reductions of 2 mg on alternating intervals of 1 and 2 weeks.
Magnitude Group	Magnitude Group	Subjects will receive alternating reductions of 1 mg or 2 mg weekly.

Primary Outcome Measures

Name	Time	Method
Visual Analog Scale (VAS) Scores	36 weeks	The VAS questionnaire consists of 4 questions related to cravings (0 = not at all to 10 = very much), withdrawal (0 = no symptoms to 10 = symptoms all day), sleep quality (0 = best to 10 = worst), and sleep duration (0 = longest ever to 10 = shortest ever). The 4 component questions are summed to provide a single VAS score for that day. The daily scores are averaged over the week or for two weeks depending on how often the dose was changed. The average VAS scores for each reduction regimen are averaged and compared to the alternative dosing group.

Trial Locations

Locations (2)

Univerity of Pittsburgh Magee-Womens Hospital; 🇺🇸 Pittsburgh, Pennsylvania, United States

High Risk Obstetrical Consultants; 🇺🇸 Knoxville, Tennessee, United States