rTMS, Stress and Opioid Use Disorder

NCT04920864 | Active Not Recruiting FDA Device

• 1 other identifier: IRB-21-01-3111
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

Opioid agonist treatments are the gold standard for treating opioid use disorder (OUD). Yet, even effective treatments average only 50% six-month retention. Despite extensive research into treatment options, it remains important to improve understanding of factors that contribute to relapse and identify interventions to mitigate these risks. Stress-exposure is problematic for people trying to recover from substance use disorders (SUDs) because it weakens inhibition of automatic behaviors and increases drug craving and likelihood of relapse. However, paths through which stress affects behavior are incompletely understood and current SUD treatments do not target effects of stress on drug use. This project will explore whether repetitive transcranial magnetic stimulation (rTMS) might improve treatment outcomes for people with OUD entering methadone treatment. The investigators will examine the impact of rTMS treatment over one of two theoretically-driven neural targets on substance use and cognitive outcomes associated with treatment success (executive function and emotional arousal).

Conditions

Opioid Use Disorder

Outcome Measures

Primary Outcomes (4)

• Wisconsin Card Sorting Task perseverance score

  Wisconsin Card Sorting Task perseverance measures cognitive flexibility as an index of executive function. Higher scores reflect better outcome.

  change from pre-intervention (day 0) to post-intervention (day 5) in the sham and active conditions

• Emotional Arousal task rating

  Average unpleasantness and arousal ratings in response to aversive pictures from the International Affective Picture System (IAPS). Lower unpleasantness and arousal scores reflect better outcome.

  change from pre-intervention (day 0) to post-intervention (day 5) in the sham and active conditions

• Opioid progressive ratio breakpoint

  Opioid ($10 unit dose) vs. money ($2) hypothetical 10-trial choice task progressive ratio breakpoint is the highest response requirement completed for the drug on an exponentially increasing schedule of reinforcement, where the subject has to click the mouse an increasing number of times to earn drug or money. Lower breakpoint scores reflect better outcome.

  change from pre-intervention (day 0) to post-intervention (day 5) in the sham and active conditions

• Treatment success

  Number of days of opioid use (based on timeline followback interview) during the 7 days following each 5-day rTMS (active and sham) period. Fewer days of opioid use reflect better outcome.

  change from sham to active condition (randomized to occur on days 6-12 and 18-24, respectively)

Secondary Outcomes (4)

• Digit Span total score

  change from pre-intervention (day 0) to post-intervention (day 5) in the sham and active conditions

• Monetary delay discounting

  change from pre-intervention (day 0) to post-intervention (day 5) in the sham and active conditions

• State-Trait Anxiety Inventory state anxiety total score

  change from pre-intervention (day 0) to post-intervention (day 5) in the sham and active conditions

• Positive and Negative Affect Scale total score

  change from pre-intervention (day 0) to post-intervention (day 5) in the sham and active conditions

Study Arms (4)

Active 10 Hz dlPFC rTMS

EXPERIMENTAL

10 Hz dorsolateral prefrontal cortex stimulation for 10 sessions (2 sessions/day X 5 days)

Device: rTMS

Sham dlPFC rTMS

SHAM COMPARATOR

inactive dorsolateral prefrontal cortex stimulation for 10 sessions (2 sessions/day X 5 days)

Device: rTMS

Active 1 Hz mPFC rTMS

EXPERIMENTAL

1 Hz medial prefrontal cortex stimulation for 10 sessions (2 sessions/day X 5 days)

Device: rTMS

Sham mPFC

SHAM COMPARATOR

inactive medial prefrontal cortex stimulation for 10 sessions (2 sessions/day X 5 days)

Device: rTMS

Interventions

rTMS DEVICE

Repetitive transcranial magnetic stimulation

Active 1 Hz mPFC rTMS; Active 10 Hz dlPFC rTMS; Sham dlPFC rTMS; Sham mPFC

Eligibility Criteria

• Age: 21 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Meet DSM-5 criteria for OUD;
• In methadone or buprenorphine treatment
• Age 21-70 yr;
• Right handed;
• Males and non-pregnant/non-lactating females;
• Cognitively intact (total IQ score \>80);
• Use alcohol and/or marijuana \<4 times per week; each "time" should consist of \<2 marijuana "joint" equivalent and \<4 alcoholic drinks.

You may not qualify if:

• Acutely under the influence of any substance (except methadone or buprenorphine) during session;
• Current, regular (\>2 times/week) use of illicit drugs other than opioids (except cannabis);
• Any past 24 hour use of drugs other than opioids or nicotine;
• Urinalysis positive for pregnancy;
• Medical conditions prohibiting use of rTMS;
• Lifetime psychotic, bipolar, or potentially antisocial personality disorder;
• Untreated or uncontrolled past-year diagnosis of major depression, generalized anxiety disorder, obsessive compulsive disorder, or post traumatic stress disorder;
• Past-month SUD other than OUD or tobacco use disorder;
• Acute/unstable illness making it unsafe for participation;
• Any prohibited medications including: medications that lower seizure threshold, certain psychiatric medications, or prescription pain medications;
• Chronic head or neck pain;
• Past-month participation in a research study.

Sponsors & Collaborators

• Wayne State University: lead

Study Sites (1)

Tolan Park Medical Building

Detroit, Michigan, 48201, United States

Location

MeSH Terms

Conditions

Opioid-Related Disorders

Condition Hierarchy (Ancestors)

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

Study Officials

• Mark K Greenwald, PhD

  Wayne State University

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Sham rTMS will consist of inactive figure of 8 coil. The participant, rTMS administrator, and assessors will all be blind to coil type.
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Psychiatry and Behavioral Neurosciences; and Director, Substance Abuse Research Division

Model Details: A mixed design study will be used to examine the effects of active rTMS vs. sham (within subject) over one of two locations: 10 Hz dlPFC rTMS (group 1) or 1 Hz mPFC rTMS (group 2) in subjects receiving methadone treatment for OUD. The general rTMS treatment protocol will be the same for both groups and will consist of 2 stimulation sessions per day, separated by \~30min, for 5 days (10 total stimulation sessions per treatment protocol). The sham protocol will be the same except the sham rTMS coil will be used. Participants will be randomly assigned to groups and complete the 2 conditions (active vs. sham rTMS) in random order.

Study Record Dates

• First Submitted: May 30, 2021
• First Posted: June 10, 2021
• Study Start: April 1, 2022
• Primary Completion: August 8, 2024
• Study Completion (Estimated): December 1, 2026
• Last Updated: December 30, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)