Pharmacologically-based Strategies for Opioid Substitution Therapy During Pregnancy

NCT ID: NCT03831113

Last Updated: 2024-08-29

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 13 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-04-13
• Study Completion Date: 2022-12-22

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

Conditions

Opiate Addiction; Pregnancy

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Magnitude Group

Subjects will receive alternating reductions of 1 mg or 2 mg weekly.

Group Type: ACTIVE_COMPARATOR

Magnitude Group

Intervention Type: DRUG

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.

Frequency Group

Subjects will receive dose reductions of 2 mg on alternating intervals of 1 and 2 weeks.

Group Type: ACTIVE_COMPARATOR

Frequency Group

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: 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.

Intervention Type: DRUG

Other Intervention Names

magnitude; frequency

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

NIH

Sponsor Role: collaborator

Steve N. Caritis, MD

OTHER

Sponsor Role: lead

Responsible Party

Steve N. Caritis, MD

Professor, Department of OB/Gyn/RS

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Steve Caritis, MD

Role: PRINCIPAL_INVESTIGATOR

University of Pittsburgh

Locations

Univerity of Pittsburgh Magee-Womens Hospital

Pittsburgh, Pennsylvania, United States

High Risk Obstetrical Consultants

Knoxville, Tennessee, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

R01HD096796

Identifier Type: NIH

Identifier Source: secondary_id

View Link

STUDY19100128

Identifier Type: -

Identifier Source: org_study_id