Pharmacologically-based Strategies for Opioid Substitution Therapy During Pregnancy

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.

Study Overview

• Status: Terminated
• Conditions: Pregnancy; Opiate Addiction
• Intervention / Treatment: Drug: Magnitude Group; Drug: Frequency Group

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 Type: Interventional
• Enrollment (Actual): 13
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • Univerity of Pittsburgh Magee-Womens Hospital
  • Tennessee
    • Knoxville, Tennessee, United States, 39720
      • High Risk Obstetrical Consultants

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Magnitude Group; Subjects will receive alternating reductions of 1 mg or 2 mg weekly.	Drug: Magnitude Group; Dose reductions will alternate between 1mg or 2 mg weekly until the subject is no longer taking buprenorphine or is at the lowest tolerable dose.; Other Names: magnitude
Active Comparator: Frequency Group; Subjects will receive dose reductions of 2 mg on alternating intervals of 1 and 2 weeks.	Drug: Frequency Group; Dose reductions of 2 mg will occur alternate between once weekly to biweekly until the subject is no longer taking buprenorphine or is at the lowest tolerable dose.; Other Names: frequency

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Visual Analog Scale (VAS) Scores	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.	36 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Urine toxicology screen	Urine toxicology screens will be performed during the weekly clinic visits to confirm that the subject is compliant with the study requirements.	4.5 years

Collaborators and Investigators

• Sponsor: Steve N. Caritis, MD
• Collaborators: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
• Investigators: Principal Investigator: Steve Caritis, MD, University of Pittsburgh

Study record dates

Study Major Dates

• Study Start (Actual): April 13, 2019
• Primary Completion (Actual): December 22, 2022
• Study Completion (Actual): December 22, 2022

Study Registration Dates

• First Submitted: January 22, 2019
• First Submitted That Met QC Criteria: February 4, 2019
• First Posted (Actual): February 5, 2019

Study Record Updates

• Last Update Posted (Actual): August 29, 2024
• Last Update Submitted That Met QC Criteria: August 23, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Keywords: Buprenorphine; medication-assisted treatment (MAT) programs
• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Substance-Related Disorders; Narcotic-Related Disorders; Opioid-Related Disorders; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Opioid; Narcotics; Narcotic Antagonists; Buprenorphine
• Other Study ID Numbers: STUDY19100128; R01HD096796 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No