Longitudinal Neural Fingerprinting of Opioid-use Trajectories

This project aims to collect a densely sampled neuroimaging dataset among individuals receiving medications for opioid use disorder (MOUD). MOUD is multiphasic, comprised of medication induction, stabilization, ongoing treatment, and eventual dis-continuation phases. However, with a few small exceptions, existing neuroimaging efforts are almost exclusively single time-point assessments which, by definition, fail to capture these clinically relevant transitions and thus also do not capture individual risk and resilience trajectories. The investigators innovation, the characterization of neurocomputational trajectories during clinically relevant phases of MOUD treatment, will provide unprecedented mechanistic insight into the neurobiological basis of recovery. Once characterized, such trajectories may be used in the identification of specific therapeutic windows for additional intervention (e.g., times of increased neural plasticity) and in the design of novel tailored interventions based on known brain mechanisms (e.g., behavioral therapy, neurostimulation, neurofeedback).

Study Overview

• Status: Recruiting
• Conditions: Opioid Use Disorder
• Intervention / Treatment: Diagnostic test: fMRI

Detailed Description

MOUD individuals between the ages of 18 and 50 who recently enrolled in methadone treatment at APT Foundation clinics in the greater New Haven area. Investigators will aim to recruit individuals as early as possible in treatment, but individuals may be within the first 6 months of treatment at the time of screening, as this may be necessary to ensure that they are on a stable dose of methadone.

AIM 1 - Longitudinal neural fingerprinting of MOUD to repeatedly characterize neural trajectories of individuals in early methadone treatment.

AIM 2 - Complementary, longitudinal computational phenotyping of MOUD to repeatedly characterize behavioral, computational trajectories of individuals in early methadone treatment.

After participation in the main study, participants will be asked to complete a 15-minute follow up every month for an additional three months.

• Study Type: Interventional
• Enrollment (Estimated): 10
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Sarah Yip, PhD, MSc; Phone Number: 203 704 7588; Email: sarah.yip@yale.edu

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06520
      • Recruiting
      • MRRC at The Anlyan Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• within the first 6 months of methadone treatment for OUD and on a stable dose of methadone
• eligibility for MRI scanning
• willing to commit to longitudinal study visits

Exclusion Criteria:

• current psychosis, mania, or suicidal ideation with intent, as assessed during screening with the SCID-5
• current co-occurring severe substance-use disorders (excluding nicotine and opioids), as assessed during screening with the SCID-5
• current intoxication or acute withdrawal at time of study visit sufficient to prevent participation based on: behavioral observation, breathalyzer, and SOWS assessment (these individuals will be allowed to enroll at a later date once stable)
• severe cognitive impairment (determined through consent process conducted by trained clinical research staff and during consent quiz or as indicated by a PROMIS Cognitive Function t-score <30 (i.e., score indicating severe impairment)
• Past or present history of intellectual disability or developmental disorder
• Neurological disease (including seizures or epilepsy) as assessed by self-report and by consulting clinic records
• Head trauma with loss of consciousness of more than 30 minutes
• Organ dysfunction or any unstable or untreated medical conditions that may alter cerebral function or interfere with study participation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: neural fingerprinting of MOUD; Study participants will have one in-person screening (2 hours), 6 in-person visits for fMRI scans conducted biweekly (4 hours), and will be computationally assessed 12 times, once per week for 12 weeks. After participation in the main study, participants will be asked to complete a 15-minute follow up every month for an additional three months	Diagnostic test: fMRI; Participants will be performing tasks while undergoing fMRI. Tasks include Stroop task, Emotion-regulation task and an Ambiguity reward task. There will also be a Resting state: Participants are not presented with any specific stimulus.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Relationship between functional connectivity within canonical neural networks and within the 'opioid abstinence network' and opioid use	Relationship between functional connectivity within canonical neural networks and within the 'opioid abstinence network' and opioid use over 6 biweekly sessions. Functional connectivity is computed as the Pearson's correlation between two brain regions, or 'nodes'. This will be done in a pairwise manner to obtain connectivity values for all possible node pairs in the Shen atlas, a 268-node atlas covering the cortex, subcortex and cerebellum. Correlation coefficients are transformed to Z-scores using Fisher's r-to-z transformation. Connectivity within a given network is defined as the mean of the Z values for all of the edges (connection between two node pairs) within the network.	up to 12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Presence or absence of opioid use	Relationship between performance on the risk and ambiguity task and opioid use over 12 weekly sessions. Parameters are computed from the participant's choice data during task performance at each weekly time point. The primary task parameter is α. This is a participant-specific known-risk tolerance parameter.	up to 12 weeks

Collaborators and Investigators

• Sponsor: Yale University
• Collaborators: National Institute on Drug Abuse (NIDA)
• Investigators: Principal Investigator: Sarah Yip, PhD, MSc, Yale University

Study record dates

Study Major Dates

• Study Start (Actual): October 10, 2024
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): January 1, 2027

Study Registration Dates

• First Submitted: December 19, 2023
• First Submitted That Met QC Criteria: January 10, 2024
• First Posted (Actual): January 16, 2024

Study Record Updates

• Last Update Posted (Actual): May 27, 2026
• Last Update Submitted That Met QC Criteria: May 21, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Medication for Opioid Use Disorder (MOUD)
• Additional Relevant MeSH Terms: Narcotic-Related Disorders; Mental Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Opioid-Related Disorders; Diagnostic Techniques and Procedures; Diagnosis; Tomography; Diagnostic Imaging; Magnetic Resonance Imaging
• Other Study ID Numbers: 2000036564; 1R21DA058415-01A1 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: This study will submit and share data with OpenNeuro. This will include de-identified demographic data, neuropsychological assessment data, clinical assessment data, and fMRI data (raw).
• IPD Sharing Time Frame: All data will be deposited to OpenNeuro starting 24 months after data collection begins and will be deposited every six months thereafter. OpenNeuro policy states that any data uploaded to their repository becomes publicly available under a Creative Commons CC0 license after a 36-month period beginning from first successful version of the dataset.
• IPD Sharing Access Criteria: OpenNeuro policy states that any data uploaded to their repository becomes publicly available under a Creative Commons (CC) license after a 36-month period beginning from first successful version of the dataset. Users create an account with OpenNeuro account in order to download BIDS formatted files and any associated metadata.

Drug and device information, study documents

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