TOTS: rTMS, Stress and Opioid Use Disorder
Study Details
Study Description
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).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
N/A |
Detailed Description
The Competing Neurobehavioral Decisions Systems (CNDS) model of addiction suggests that people with SUDs have altered function and connectivity in fronto-cortical executive control regions (e.g. dorsolateral prefrontal cortex [dlPFC]) and fronto-cortical limbic control regions (e.g. medial prefrontal cortex [mPFC]). Namely, elevated activity in limbic circuitry results in hypersensitivity to drug cues and stress, and decreased executive control impairs the ability to resist drug urges. The CNDS theoretical framework can guide selection and testing of rTMS targets that could improve understanding of the mechanisms of SUDs and stress-induced drug use. Results from previous research suggest that therapeutic effects of rTMS for SUD could occur via excitation of dlPFC or inhibition of mPFC.
The investigators will administer excitatory (10Hz) dlPFC rTMS and inhibitory (1Hz) mPFC rTMS (through an electromagnetic coil placed against the scalp) coupled with tasks of executive function and emotional arousal during stress and neutral conditions (guided imagery task using personalized scripts) in adults with OUD early in methadone treatment. The investigators will examine and compare how strengthening dlPFC activity or reducing mPFC activity may reverse stress-induced executive and emotional dysfunction, respectively, and improve treatment outcomes in persons with OUD seeking to abstain from opioid use.
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. Immediately prior to and after each 5-day rTMS treatment protocol, participants will attend an assessment visit when they will complete multiple tasks during both stress (guided imagery stressor) and neutral conditions. These tasks are designed to measure executive function, emotional arousal, and drug-seeking behavior.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Active 10 Hz dlPFC rTMS 10 Hz dorsolateral prefrontal cortex stimulation for 10 sessions (2 sessions/day X 5 days) |
Device: rTMS
Repetitive transcranial magnetic stimulation
|
| Sham Comparator: Sham dlPFC rTMS inactive dorsolateral prefrontal cortex stimulation for 10 sessions (2 sessions/day X 5 days) |
Device: rTMS
Repetitive transcranial magnetic stimulation
|
| Experimental: Active 1 Hz mPFC rTMS 1 Hz medial prefrontal cortex stimulation for 10 sessions (2 sessions/day X 5 days) |
Device: rTMS
Repetitive transcranial magnetic stimulation
|
| Sham Comparator: Sham mPFC inactive medial prefrontal cortex stimulation for 10 sessions (2 sessions/day X 5 days) |
Device: rTMS
Repetitive transcranial magnetic stimulation
|
Outcome Measures
Primary Outcome Measures
- Wisconsin Card Sorting Task perseverance score [change from pre-intervention (day 0) to post-intervention (day 5) in the sham and active conditions]
Wisconsin Card Sorting Task perseverance measures cognitive flexibility as an index of executive function. Higher scores reflect better outcome.
- Emotional Arousal task rating [change from pre-intervention (day 0) to post-intervention (day 5) in the sham and active conditions]
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.
- Opioid progressive ratio breakpoint [change from pre-intervention (day 0) to post-intervention (day 5) in the sham and active conditions]
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.
- Treatment success [change from sham to active condition (randomized to occur on days 6-12 and 18-24, respectively)]
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.
Secondary Outcome Measures
- Digit Span total score [change from pre-intervention (day 0) to post-intervention (day 5) in the sham and active conditions]
Digit Span (forward and backward) measures the extent of verbal working memory as an index of executive function. Higher scores reflect better outcome.
- Monetary delay discounting [change from pre-intervention (day 0) to post-intervention (day 5) in the sham and active conditions]
Brief version of delay discounting task measures the immediate vs. delayed value of money. Higher area-under-the-curve scores (preference for delayed money) reflect better outcome.
- 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]
State anxiety subscale score of the State-Trait Anxiety Inventory. Lower scores reflect better outcome.
- Positive and Negative Affect Scale total score [change from pre-intervention (day 0) to post-intervention (day 5) in the sham and active conditions]
Positive and Negative Affect Scale measures both positive and negative affect. Lower total negative affect scores reflect better outcome.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Meet DSM-5 criteria for OUD;
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Receiving methadone treatment for 1-3 months
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Age 21-60 yr;
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Right handed;
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Males and non-pregnant/non-lactating females;
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Cognitively intact (total IQ score >80);
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Use alcohol and/or marijuana <3 times per week; each "time" should consist of <1 marijuana "joint" equivalent and <3 alcoholic drinks.
Exclusion Criteria:
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Acutely under the influence of any substance (except methadone) during session;
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Past 7-day use of illicit drugs (not including cannabis) other than opioids;
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Urinalysis positive for cocaine, benzodiazepines, barbiturates, amphetamines, or pregnancy;
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Medical conditions prohibiting use of rTMS;
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Lifetime psychotic, bipolar, generalized anxiety, or obsessive compulsive disorder;
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Major depression or suicidality in the past 5 years
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Past-year SUD other than OUD or tobacco use disorder;
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Acute/unstable illness making it unsafe for participation;
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Any prohibited medications;
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Chronic head or neck pain;
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Past-month participation in a research study.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Tolan Park Medical Building | Detroit | Michigan | United States | 48201 |
Sponsors and Collaborators
- Wayne State University
Investigators
- Study Director: Mark K Greenwald, PhD, Wayne State University
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- IRB-21-01-3111