Opiate Addiction, Pregnancy
Conditions
Keywords
Buprenorphine, medication-assisted treatment (MAT) programs
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
Interventions
DRUGMagnitude 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.
DRUGFrequency 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.
Sponsors
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Steve N. Caritis, MD
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
dose reductions will alternate between 1 or 2 mg weekly (magnitude group) or 2 mg reductions every 1 or 2 weeks (frequency group)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 45 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Participant flow
Recruitment details
Recruitment occurred in two Medication Assisted Treatment clinics either in Pittsburgh or in Knoxville.Recruitment started on 4/13/2019 and ended on 12/22/2022. All participants at the Tennessee site were assigned to the frequency group
Participants by arm
| Arm | Count |
|---|---|
| Magnitude Group Subjects will receive alternating reductions of 1 mg and then 2 mg weekly. Dose reductions will continue until the subject is no longer taking buprenorphine or is at the lowest tolerable dose. | 1 |
| Frequency Group Subjects will receive dose reductions of 2 mg on alternating intervals of 1 and 2 weeks. Dose reductions will continue until the subject is no longer taking buprenorphine or is at the lowest tolerable dose. | 12 |
| Total | 13 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Protocol Violation | 0 | 9 |
| Overall Study | Withdrawal by Subject | 0 | 2 |
Baseline characteristics
| Characteristic | Frequency Group | Total | Magnitude Group |
|---|---|---|---|
| Age, Continuous | 32.4 years STANDARD_DEVIATION 6.1 | 31.8 years STANDARD_DEVIATION 6.1 | 26 years STANDARD_DEVIATION 0 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1 Participants | 2 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 1 Participants | 2 Participants | 1 Participants |
| Sex: Female, Male Female | 1 Participants | 2 Participants | 1 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 1 | 0 / 12 |
| other Total, other adverse events | 0 / 1 | 0 / 12 |
| serious Total, serious adverse events | 0 / 1 | 0 / 12 |
Outcome results
Primary
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.
Time frame: 36 weeks
Population: only those compliant with protocol were analyzed
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Magnitude Group | Visual Analog Scale (VAS) Scores | 1 mg or 1 week cycle | 2.11 score on a scale | Standard Deviation 0.12 |
| Magnitude Group | Visual Analog Scale (VAS) Scores | 2 mg or 2 week cycle | 1.94 score on a scale | Standard Deviation 0.23 |
| Frequency Group | Visual Analog Scale (VAS) Scores | 1 mg or 1 week cycle | .43 score on a scale | Standard Deviation 0.13 |
| Frequency Group | Visual Analog Scale (VAS) Scores | 2 mg or 2 week cycle | .43 score on a scale | Standard Deviation 0.13 |