Neuroplasticity in Maternal Opioid Use Disorder (OUD)

NCT05495984 | Recruiting DMC

• 1 other identifier: 2000033065
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

Opioid use disorder (OUD) remains a major public health problem particularly for mothers in the perinatal period, for whom stress, relapse rates, and risk for overdose are elevated. The perinatal period is characterized by significant neural reorganization that determines outcomes for mothers and infants. OUD is also associated with neural reorganization, specifically neural circuitry implicated in stress regulation and reward processes. Interventions should therefore take advantage of this changing perinatal biology to enhance treatment response by targeting the aberrant neural circuitry compromised by maternal OUD. The investigators have developed and refined an evidence-based intervention for mothers with OUD designed to target these neural mechanisms and enhance the reward of caregiving; however, this has yet to be formally tested. Therefore, the investigators will examine maternal neuroplasticity using high-dense array electroencephalography (EEG) in mothers with OUD in response to our intervention. There will be 1 laboratory visit at pre-treatment, followed by 12 sessions of the evidence-based parenting intervention, and 1 laboratory visit at post-treatment. This study will attempt to validate the importance of taking advantage of the neuroplasticity in the perinatal period to optimize outcomes for mothers with OUD.

Conditions

Opioid Use Disorder

Outcome Measures

Primary Outcomes (5)

• Change in mothers' Event-related potentials (ERPs) elicited by unknown infant face and cry stimuli

  E-Prime 2.0 software will present visual and auditory stimuli in an experimental paradigm lasting approximately 30 minutes. Continuous electroencephalography (EEG) will be recorded using Net Station 4.2.1. Net Station 4.5 will be used to pre-process EEG data (first be digitally filtered, then segmented into 1-second epochs (100ms pre- and 900ms post-stimulus onset). Net Station artifact detection will be set to detect artifact. Spline interpolation will be used to replace channels with artifacts in more than 40% of trials. Ocular Artifact Removal (OAR), using a blink slope threshold of 14µV/ms, will be applied to data for all participants. EEG data will next be re-referenced to the average reference of all electrodes and baseline corrected to the 100ms interval pre-stimulus onset. Lastly, the EEG data will be averaged across stimulus conditions for each participant. The N170, N100, and P300 will be visually inspected in the grand-averaged data and verified for each participant.

  Week 1 and Week 14

• Change in maternal mentalization measured by coding of reflective functioning (RF) on the one-hour Parent Development Interview (PDI)

  The PDI is a semi-structured interview with 19 questions eliciting a parent's verbal narrative about common emotionally-challenging aspects of parenting. The interview is recorded, transcribed, and each of the 19 responses is rated on a 10-point scale where: a score of 1 indicates complete absence of recognition of mental states (events are described solely in terms of behavior) and scores above 5 indicate increasingly elaborate and sophisticated understanding of how mental states function and influence behavior. Reliable coders assign an Overall Score to the protocol that represents the parent's modal level of response. The PDI requires approximately 60 minutes to complete.

  Week 1 and Week 14

• Change in mothers' reflective functioning assessed using the self-report Parental Reflective Functioning Questionnaire (PRFQ)

  The PRFQ is an 18-item self-report questionnaire to quantify levels of 3 key components of parental RF: Interest \& Curiosity surrounding their child's mental states, Certainty in the recognition of their child's mental states, and Pre-Mentalizing or difficulty in considering the child's mental states. Optimal RF is indicated by higher scores on the interest and curiosity subscale, moderate scores on the certainty subscale, and lower scores on the pre-mentalizing subscale. Participants rate their responses on a 7-point likert scale ranging from 1 (strongly disagree) to 7 (strongly agree). The PRFQ requires approximately 10 minutes to complete.

  Week 1 and Week 14

• Change in mothers' certainty about mental states assessed using the self-report Certainty about Mental States Questionnaire (CAMSQ)

  The CAMSQ is a psychometrically sound 20-item self-report questionnaire. The CAMSQ assesses two maladaptive variants of subjective certainty about mental states that can be linked to hypomentalizing and hypermentalizing. The CAMSQ yields two subscales representing certainty about one's own metal states, and certainty about others' mental states. Items are scored by taking the mean of item responses (never = 1, almost never = 2, sometimes = 3, half of the time = 4, often = 5, almost always = 6, always = 7). The CAMSQ requires approximately 15 minutes to complete.

  Week 1 and Week 14

• Change in mothers' mind-mindedness assessed using the Five-Minute Speech Sample (MM)

  On the five-minute speech sample, mothers will be asked to describe their child for five minutes; responses will be recorded, transcribed, and coded using the representational MM coding manual. Descriptions that refer to mental states (e.g., cognitions, emotions, desires, interests) are identified as mind-minded. The frequency of mind-minded comments will be calculated, as will the proportion of mind-minded to non- mind-minded comments, to control for verbosity.

  Week 1 and Week 14

Secondary Outcomes (9)

• Mothers' baseline substance use assessed using the Addiction Severity Index (ASI-Lite)

  Week 1

• Change in mothers' depression assessed using the Edinburgh Postnatal Depression Scale (EPDS)

  Week 1 and Week 14

• Change in mothers' depression assessed using the Patient Health Questionnaire-2 (PHQ-2)

  Week 1 and Week 14

• Change in mothers' anxiety assessed using the Generalized Anxiety Disorder-7 (GAD-7)

  Week 1 and Week 14

• Change in mothers' stress assessed using the Parenting Stress Index- Short Form (PSI-SF)

  Week 1 and Week 14

Study Arms (2)

Primary Objective: Event-Related Potentials (ERPs)

EXPERIMENTAL

Use ERPs elicited by unknown infant face and cry stimuli to determine whether neural markers translate to maternal mentalization in mothers with opioid use disorder (OUD) at 4-12 months postpartum

Behavioral: ERPs with electroencephalography (EEG)

Secondary Objective: ERPs + Mothering from the Inside Out (MIO)

EXPERIMENTAL

Use Event-Related Potentials (ERPs) elicited by unknown infant face and cry stimuli to determine whether neural response changes with participation in an evidence-based parenting intervention designed specifically for mothers with OUD: Mothering from the Inside Out (MIO).

Behavioral: ERPs with electroencephalography (EEG); Behavioral: MIO

Interventions

ERPs with electroencephalography (EEG) BEHAVIORAL

E-Prime 2.0 software will present visual and auditory stimuli in an experimental paradigm lasting approximately 30 minutes (ERPs). Visual stimuli will include photographs of color photographs of unfamiliar infants (aged 5- 10 months) balanced for ethnicity (Black/White) and gender (male/female) displaying happy neutral, and sad affective expressions. Auditory stimuli will include 2-second audio clips of high-distress and low-distress infant cries. Experimental procedure: Trials will consist of a central fixation cross (jittered 400-600ms), stimulus presentation (500ms faces, 2000ms cries), and blank screen (1000ms). Continuous electroencephalography (EEG) will be recorded using Net Station 4.2.1. A 128 Ag/Silver Chloride (AgCl) electrode net will be soaked in a warm potassium chloride solution, and net electrodes will be spaced evenly and symmetrically on each participant's head to cover the scalp.

Primary Objective: Event-Related Potentials (ERPs); Secondary Objective: ERPs + Mothering from the Inside Out (MIO)

MIO BEHAVIORAL

A 12-week, manualized, individual parenting psychotherapy developed specifically for mothers with addictions administered by the Principal Investigator. It is designed to foster a mother's capacity for mentalization or reflective functioning (RF). MIO is offered in conjunction with standard addiction treatment.

Secondary Objective: ERPs + Mothering from the Inside Out (MIO)

Eligibility Criteria

• Age: 21 Years - 45 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Biological mother of infants between 4-months and 12-months of age
• years of age at time of recruitment
• Enrolled in substance use treatment and on mediation for opioid use disorder (MOUD).

You may not qualify if:

• Incapable of giving informed consent
• Child spends less than 50% of time in mother's custody.
• Non-English-speaking
• Unable to complete the study because of pending legal cases or unable to supply two forms of contact for the purpose of follow-up
• Physiological addiction to a substance that requires detoxification, defined as difficulties with physiological withdrawal from substances (e.g. delirium tremens, shaking, nausea).

Sponsors & Collaborators

• Yale University: lead
• Alkermes, Inc.: collaborator

Study Sites (1)

Yale Child Studies Center

New Haven, Connecticut, 06520, United States

RECRUITING

MeSH Terms

Conditions

Opioid-Related Disorders

Interventions

Evoked Potentials

Condition Hierarchy (Ancestors)

Narcotic-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Cortical Excitability; Electrophysiological Phenomena; Physiological Phenomena; Nervous System Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena

Study Officials

• Amanda Lowell, Ph.D.

  Yale University

  PRINCIPAL INVESTIGATOR

• Helena Rutherford, PhD

  Yale University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Amanda Lowell, PhD

CONTACT

321-277-2516; amanda.lowell@yale.edu

Helena Rutherford, PhD

CONTACT

203-737-3408; helena.rutherford@yale.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: All participants (n=15) will complete Study Visit 1 for the Primary Objective, and Study Visits 2-14 for the Secondary Objective.

Study Record Dates

• First Submitted: August 8, 2022
• First Posted: August 10, 2022
• Study Start: January 1, 2023
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): June 1, 2026
• Last Updated: October 29, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)