An Open-Label Trial of Repetitive Transcranial Magnetic Stimulation for Opioid Use Disorder

Study Overview
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Brief Summary
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The purpose of this study is to understand the role of repetitive Transcranial Magnetic Stimulation (rTMS) in reducing opioid and other substance use and craving and improving thinking skills.

Detailed Description
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The overarching goal of this study is to investigate a form of neuromodulation, rTMS, as an adjunctive treatment for OUD by evaluating the impact of rTMS on substance use, craving and inhibitory control, factors which contribute to relapse. The primary outcome will be the assessment of whether rTMS reduces substance use. Additional exploratory outcomes include the assessment of whether rTMS applied to the DLPFC provides neuromodulatory effects through the assessment of craving, inhibitory control, and functional connectivity via MRI. The targeted sample size for this open-label study, where all enrolled subjects will receive 9 sessions of active rTMS over 3 weeks.

Official Title
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An Open-Label Trial of Repetitive Transcranial Magnetic Stimulation for Opioid Use Disorder

Conditions
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Opioid-use Disorder, Substance-Related Disorders, Chemically-Induced Disorders, Mental Disorder

Intervention / Treatment
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* Device: Repetitive Transcranial Magnetic Stimulation (rTMS)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Able to provide written informed consent, and to comply with study procedures. Be actively enrolled in the COAT Program Meet DSM-V criteria for a primary OUD assessed via structured clinical interview Columbia-Suicide Severity Rating Scale score < 4 Be abstinent from opioids (other than prescribed buprenorphine/naloxone) and illicit substances other than marijuana at the time of the enrollment, confirmed via urine drug screen Willing to practice contraception to avoid pregnancy the duration of the study Exclusion Criteria: Medical conditions that preclude rTMS: including vasodepressor syncope, glaucoma, increased intracranial pressure, cardiac disease, migraine disorder, cerebral vascular events (cerebral vascular accident, transient ischemic attack), any brain lesions (such multiple sclerosis), brain injury, seizure disorder (or family history) of any type, and have cardiac pacemakers or implanted medication pumps DSM-V criteria for major psychiatric illness other than depression Major Cognitive Disorder (as evidenced by a score of <21/30 on the Mini Mental Status Exam (MMSE) Pregnancy Positive responses to the TMS Adult Safety Screen or the MRI checklist Intracranial metallic objects (excluding dental fillings) Uncorrected visual acuity problems Mobility limitations Clinically significant EKG abnormalities (including QTc interval prolongation >450 ms in men or >480 ms in women) Unwillingness to abstain from prescribed drugs Prior rTMS treatment Other mental or physical conditions that, in the PI's opinion, would be inappropriate for study participation. Intake of one or a combination of the following drugs forms a 'Strong Potential Hazard' for application of rTMS due to their significant seizure threshold lowering potential: Imipramine, Amitriptyline, Doxepine, Nortriptyline, Maprotiline, Chlorpromazine, Clozapine, Foscarnet, Ganciclovir, Ritonavir, Amphetamines, Cocaine (MDMA, ecstasy), Phencyclidine (PCP, angel's dust), Ketamine, Gamma-hydroxybutyrate (GHB), Alcohol, Theophylline. The inclusion of a patient on any of the above medication will be carefully evaluated and a decision documented by the medically responsible physician. The risk is dependent on the patient's past medical history, drug dose, speed of dose increase (or decrease), history of recent medication changes or duration of treatment, and combination with other CNS active drugs. Recent withdrawal from one of the following drugs forms a 'Strong Relative Hazard' for application of rTMS due to the resulting significant seizure threshold lowering potential: Alcohol, Barbiturates, Benzodiazepines, Meprobamate, Chloral hydrate

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: This is an open-label study for participants who have opioid use disorder (OUD) that are eligible to have repetitive transcranial magnetic stimulation (rTMS) targeting the left dorsolateral prefrontal cortex (DLPFC).
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Study Group<br>Participants will receive a type of TMS called repetitive TMS (rTMS) wherein the magnetic pulses delivered will be close together in a rapid sequence. They will receive excitatory rTMS with a stimulation frequency of 10 Hz or higher. | Device: Repetitive Transcranial Magnetic Stimulation (rTMS)<br>* During the rTMS session, an electromagnetic coil is placed against the subjects scalp. The electromagnet painlessly delivers a magnetic pulse that stimulates nerve cells in the region of the brain involved in memory and thinking.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| rTMS reduces substance use | Opioid use as measured by quantitative urine toxicology via high pressure liquid chromatography at screening, baseline, enrollment (3 times per week for 3 weeks), and follow-up phases (weekly for 4 weeks). | 1 - 7 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| rTMS applied to the DLPFC provides neuromodulatory effects | Participants will complete standardized measures of mood, drug craving, and executive function at screening, baseline, enrollment (3 times per week for 3 weeks), and follow-up phases (weekly for 4 weeks). | 1 - 7 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Transcranial Magnetic Stimulation