Pharmacologically-based Strategies for Opioid Substitution Therapy During Pregnancy

• Status: Recruiting
• Trial end date: 2023-05-31
• Target enrollment: 0
• Participant gender: Female

Summary

This study will evaluate maternal tolerance to several BUP dose reduction strategies.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Steve N. Caritis, MD; University of Pittsburgh
• Collaborator: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
• Treatments: Buprenorphine

Criteria

Specific Aim 1:

Inclusion Criteria:

1. Singleton gestation between 14-35 weeks

2. On a stable BUP dose (for at least 2 weeks) through a MAT program or just starting BUP therapy through a MAT program.

3. Willingness to consent to the study and for those on a stable BUP dose, willingness to experience mild, temporary withdrawal symptoms

Exclusion Criteria:

1. Multifetal gestation, major fetal malformation

2. Urine drug screen results positive for benzodiazepines, cocaine, heroin, barbiturates, phencyclidine (PCP), or opioids other than BUP

1. Subjects already enrolled in a MAT program must have negative urine drug screens at the Pre-Study Screening and again on the day of the PD study.

2. Subjects initiating BUP therapy will have a comprehensive drug screen performed on the day of the PD study. Results that are positive for the presence of cocaine, heroin, benzodiazepines, barbiturates, phencyclidine (PCP) or opioids other than BUP will be documented, but will not be used to determine eligibility for the study.

3. Currently taking more than one mental health medication

4. Active moderately severe depression (PHQ-9 score ≥15 or suicidal ideation)

5. Clinical signs of intoxication or mental disorientation at time of study

6. Uncontrolled hypertension

7. HIV or AIDS

8. Diagnosis of schizoaffective disorder or psychosis

Specific Aim 2:

Inclusion Criteria:

1. Singleton gestation greater than 37 0/7 weeks

2. Mother on BUP for at least 8 weeks prior to delivery.

3. Mother in a MAT program.

4. Infant with 5 minute Apgar scores >/= 6.

5. No maternal cocaine, heroin, benzodiazepines, barbiturates, phencyclidine (PCP), or opioids other than BUP in last 8 weeks of pregnancy, based on the urine drug screen results from the MAT clinic.

Exclusion Criteria:

1. Major fetal/neonatal malformation.

2. Delivery at non-study hospital.

3. Fetal growth restriction - BW < 10th percentile

4. Known fetal renal or hepatic disease that affects drug metabolism or elimination

5. Infant on ventilator support

6. HIV or AIDS

Specific Aim 3:

Part 1:

Inclusion Criteria:

1. Singleton gestation greater than 37 0/7 weeks

2. Mother on BUP for at least 12 weeks prior to delivery and compliant with clinic policies

3. Willingness to consent to the collection of biological samples; at a minimum, she must consent to a maternal hair sample, as well as a neonate hair sample and/or meconium.

4. Availability of prenatal records from Ob care provider and BUP dosing records

5. Infant with 5 minute Apgar scores ≥ 6

Exclusion Criteria:

1. Multifetal gestation

2. Major fetal malformation

3. HIV or AIDS

4. Planned delivery at another institution

5. Medical or obstetrical complications in current pregnancy including: preeclampsia, poorly controlled diabetes or hypertension, or fetal growth restriction

6. Use of cocaine, heroin, benzodiazepines, barbiturates, phencyclidine (PCP), or opioids other than BUP in the last 12 weeks of pregnancy, based on urine drug screen results from the MAT clinic

7. Currently taking more than one mental health medication

8. Active moderately severe depression (PHQ-9 score ≥15 or suicidal ideation)

9. Alcohol abuse anytime during the current pregnancy

Specific Aim 3:

Part 2:

Inclusion Criteria

1. Single gestation between 35 0/7 and 38 0/7 weeks at the time of fetal imaging

2. Mother on BUP or methadone for at least 12 weeks prior to delivery and compliant with clinic policies

3. Willingness to consent to study requirements; at a minimum, she must consent to a fetal and neonatal MRI, maternal hair sample, as well as a neonate hair sample and/or meconium.

4. Availability of prenatal records from Ob care provider and BUP or methadone dosing records

Exclusion Criteria

1. Multifetal gestation

2. Major fetal malformation

3. HIV or AIDS

4. Medical or obstetrical complications in current pregnancy including: preeclampsia, poorly controlled diabetes or hypertension, or fetal growth restriction

5. Current use of cocaine, heroin, benzodiazepines, barbiturates, phencyclidine (PCP), or opioids other than BUP or methadone based on the comprehensive urine drug screen performed within 1-2 weeks prior to the fetal MRI exam.

Use of cocaine, heroin, benzodiazepines, barbiturates, phencyclidine (PCP), or opioids other than BUP or methadone in last 12 weeks prior to the fetal MRI exam, based on urine drug screen results from the MAT clinic

6. Currently taking more than one mental health medication

7. Active moderately severe depression (PHQ-9 score ≥15 or suicidal ideation)

8. Alcohol abuse anytime during the current pregnancy

9. Any contraindication to MRI such as a pacemaker, claustrophobia, or any metallic implant

10. Current or recent (last 2 years) history of incarceration

Specific Aim 4:

Inclusion Criteria:

1. On a stable BID, TID or QID 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. Subjects on BID, TID or QID dosing, willingness to be assigned to either the Magnitude, Interval/Frequency, or Dosing group, depending on their current dosing.

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