Adversity, Brain and Opioid Use Study

A Mechanistic Investigation of Risk Factors for Opioid Use Disorder: Examining Hippocampal-based Context-dependent Learning and Memory Associated With Adverse Childhood Experiences

The way people process and remember information may be related to adverse childhood experiences and Opioid Use Disorder symptoms. The purpose of this project is to examine brain function and performance during learning and memory tasks in adults. The study will compare measures of learning and memory across three groups of participants: those with an Opioid Use Disorder (OUD) that take buprenorphine for opioid replacement therapy, adults without an Opioid Use Disorder taking buprenorphine, and healthy adults that do not have an Opioid Use Disorder and are not taking buprenorphine.

Study Overview

• Status: Not yet recruiting
• Conditions: Healthy; Opioid Use Disorder
• Intervention / Treatment: Other: Magnetic Resonance Imaging (MRI); Behavioral: Computer Tasks

• Study Type: Interventional
• Enrollment (Estimated): 315
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Mariya Churina; Phone Number: 734-232-0190; Email: AdversityBrainOUD@med.umich.edu

Study Locations

• United States
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan
      • Contact: Mariya Churina; Email: AdversityBrainOUD@med.umich.edu
      • Principal Investigator: Elizabeth Duval, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria for all groups:

• Right handed
• Able to give informed consent
• Normal/corrected-to-normal vision and hearing

Inclusion Criteria for Opioid Use Disorder (OUD) group:

• Diagnosis of OUD
• Be actively receiving buprenorphine (BUP) for opioid agonist therapy
• Be free from illicit substance use for at least 2 weeks
• The study will allow stable dose (> 3 months) of commonly prescribed psychiatric medications and some sleep aids (per protocol)

Inclusion Criteria for the BUP control group:

• Taking BUP for chronic pain
• Never had a Substance Use Disorder (including OUD)
• The study will allow stable dose (> 3 months) of commonly prescribed psychiatric medications and some sleep aids (per protocol)

Inclusion Criteria for Healthy participant group:

• Not taking BUP
• Free of any psychiatric or major medical conditions

Exclusion Criteria for all groups:

• Significant medical or neurologic conditions (e.g., stroke, seizures, multiple sclerosis)
• Actively suicidal
• Contraindication for MRI
• Life history of schizophrenia, bipolar disorder, learning disability, attention deficit disorder, or pervasive developmental disorder
• Illicit substance use (past 2 weeks)
• Prescription medications that could interfere with measures of interest (per protocol)
• Unable to provide informed consent.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Opioid use disorder (OUD) group; This group takes buprenorphine and has OUD.	Other: Magnetic Resonance Imaging (MRI); Enrolled participants will have one MRI during the study on day 2 after having Day 1 visit. During the MRI the participants will complete various tasks.; Behavioral: Computer Tasks; Eligible participants will complete computer tasks (cognitive tasks, spatial navigation tasks, context dependent fear learning, etc.) at visit 1 and then during the MRI.
Other: Buprenorphine (BUP) control group: This group takes BUP and does not have OUD.	Other: Magnetic Resonance Imaging (MRI); Enrolled participants will have one MRI during the study on day 2 after having Day 1 visit. During the MRI the participants will complete various tasks.; Behavioral: Computer Tasks; Eligible participants will complete computer tasks (cognitive tasks, spatial navigation tasks, context dependent fear learning, etc.) at visit 1 and then during the MRI.
Other: Healthy Controls group; This group does not take BUP and does not have OUD.	Other: Magnetic Resonance Imaging (MRI); Enrolled participants will have one MRI during the study on day 2 after having Day 1 visit. During the MRI the participants will complete various tasks.; Behavioral: Computer Tasks; Eligible participants will complete computer tasks (cognitive tasks, spatial navigation tasks, context dependent fear learning, etc.) at visit 1 and then during the MRI.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Differences in Blood Oxygen Level Dependent (BOLD) signal in the hippocampus	BOLD signal during functional magnetic resonance imaging (fMRI) will be used as a measure of hippocampus activation when remembering common objects and scenes. The study team will examine differences between participants with Opioid Use Disorder (OUD) and those without OUD.	Day 2 (MRI task visit)
Differences in Hippocampal (Hpc) volume	T-1 weighted structural images for each participant will be used to compute the volume of the hippocampus in people with OUD compared to those without OUD.	Day 2 (MRI task visit)
Differences in hippocampal circuit connectivity	Functional connectivity, measured with BOLD signal will be used to examine functional connectivity between the hippocampus, amygdala, and prefrontal cortex. The study team will examine differences in connectivity between participants with OUD and those without OUD.	Day 2 (MRI task visit)
Differences in performance	Number of correct responses will be used to assess memory for common objects and scenes. Differences in memory will be examined in between participants with OUD and those without OUD.	Day 1 (computer tasks visit)
Differences in performance	Number of correct responses will be used to assess memory for common objects and scenes. Differences in memory will be examined in between participants with OUD and those without OUD.	Day 2 (MRI task visit)
Differences in threat reactivity measured via skin conductance response (SCR)	Electrodermal activity collected with a bioamplifier will be used to quantify physiological reactivity to threat. Event related SCR will be measured as a baseline corrected response (peak minus baseline) to cues that predict threat compared to cues that do not predict threat. Differences in SCR between participants with OUD and participants without OUD will be examined.	Day 1 (computer tasks visit)
Differences in threat reactivity measured via skin conductance response (SCR)	Electrodermal activity collected with a bioamplifier will be used to quantify physiological reactivity to threat. Event related SCR will be measured as a baseline corrected response (peak minus baseline) to cues that predicted threat on the previous day compared to cues that did not predict threat. Differences in SCR between participants with OUD and participants without OUD will be examined.	Day 2 (MRI task visit)

Collaborators and Investigators

• Sponsor: University of Michigan
• Collaborators: National Institute on Drug Abuse (NIDA)
• Investigators: Principal Investigator: Elizabeth Duval, University of Michigan

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2024
• Primary Completion (Estimated): April 1, 2028
• Study Completion (Estimated): April 1, 2028

Study Registration Dates

• First Submitted: April 4, 2024
• First Submitted That Met QC Criteria: April 4, 2024
• First Posted (Actual): April 9, 2024

Study Record Updates

• Last Update Posted (Actual): April 9, 2024
• Last Update Submitted That Met QC Criteria: April 4, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Memory; Magnetic Resonance Imaging (MRI); Adverse Childhood Experiences; Fear Learning; Hippocampal function
• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Substance-Related Disorders; Narcotic-Related Disorders; Opioid-Related Disorders
• Other Study ID Numbers: HUM00234185; 1R01DA056415 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: It is NIH policy that the results and accomplishments of the activities that it funds should be made available to the public. The principal investigator (PI) will ensure all mechanisms used to share data will include proper plans and safeguards for the protection of privacy, confidentiality, and security for data dissemination and reuse (e.g., all data will be thoroughly de-identified and will not be traceable to a specific study participant). Plans for archiving and long-term preservation of the data will be implemented, as appropriate.
• IPD Sharing Time Frame: When the study is completed, access to study data will be provided by the PI as requested.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No