rTMS for Stimulant Use Disorders

Study Overview
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Brief Summary
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The purpose of the study is to determine feasibility of repetitive transcranial magnetic stimulation (rTMS) for individuals with moderate to severe cocaine or methamphetamine use disorder (CUD/MUD). Potential participants will be age 18-65, and interested in cutting down or stopping use. Participants will be randomized to one of two groups; groups will receive rTMS or sham rTMS (placebo) over the course of an 8-week treatment period, and complete follow-up assessments at the end of treatment, 12, and 16 weeks post-randomization.

Detailed Description
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The study will be a randomized, double-blind, sham-controlled trial comparing rTMS vs. placebo delivered over an 8-week treatment period. After assessment and inclusion into the study, participants will be randomized to receive up to 30 sessions of either rTMS or placebo treatments. The target minimum number of rTMS/placebo treatments is 20 treatments over 8 weeks. The secondary objective is to gather preliminary data on the efficacy of rTMS for individuals with moderate to severe CUD or MUD. Follow-up visits occur at end of treatment and at 12- and 16-weeks following randomization. Other study procedures: Actigraphy: To assess daily sleep quality during weeks 1-8, the ActiGraph wristband device will record, sleep latency, sleep duration, and intervals of waking during the sleep period. Electroencephalography (EEG): EEG will be obtained after randomization and again at week 4, to explore the potential for EEG to be used as a biomarker of treatment response. Cognitive-Behavioral Educational Intervention: Participants in both conditions (rTMS and placebo) will be encouraged to participate in a mobile app-based educational intervention based on principles of Cognitive Behavioral Therapy (CBT) for Substance Use Disorder (SUD). Daily Assessments: Brief, electronic remote surveys will be administered to participants daily until week 16 follow-up time point and will assess use of primary substance of abuse, craving, ability to resist use, overall mood, and self-rated sleep quality. Urine Drug Screens (UDS): UDS will be collected at screening, randomization, every treatment session, and at follow-up visits. Urine pregnancy tests: Pregnancy testing for all female participants will be performed at screening, randomization, and monthly during the treatment period. Physical exam: A physical exam will be performed at screening. Questionnaires: A battery of study assessments will be completed to further inform findings regarding feasibility and effects of rTMS on individuals with stimulant use disorders.

Official Title
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rTMS for Stimulant Use Disorders (CTN-0108)

Conditions
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Cocaine Use Disorder, Methamphetamine Abuse, Cocaine Dependence, Methamphetamine Dependence, Stimulant Use, Stimulant Abuse, Methamphetamine Use Disorder, Cocaine Abuse, Stimulant Use Disorder

Intervention / Treatment
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* Device: rTMS
* Device: Sham (Placebo)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18-65, inclusive Have a diagnosis of moderate or severe Cocaine or Methamphetamine Use Disorder (CUD/MUD) over the past 12 months (as determined by DSM-5 diagnostic criteria). Have used cocaine or methamphetamine on at least 10 of the last 30 days (based on Timeline Follow-Back). Be interested in decreasing cocaine and/or methamphetamine use. If female, willing to use appropriate birth control method during the treatment phase of the study. Be able to understand the study procedures and provide written informed consent to participate in the study. If prescribed benzodiazepines or anticonvulsants, must be on a stable dose for at least 4 weeks prior to consent. Exclusion Criteria: A Diagnostic and Statistical Manual (DSM-5) diagnosis of moderate or severe SUD of any substance other than cocaine or methamphetamine based on DSM-5. History of a serious medical disorder that, in the opinion of the Medical Clinician, would make it unsafe to participate in the study or may prevent collection of study data. Is currently engaged in formal SUD treatment. Documented history of unprovoked seizure (lifetime) or any seizure in the past 6 months. Documented history of brain lesion(s) and/or tumor(s). Metal implants or non-removable metal objects above the waist. Currently pregnant. Lifetime history of prior clinical treatment with TMS. Current or lifetime bipolar disorder. Current psychotic disorder or psychotic depression. Serious risk of homicide or suicide. Are a prisoner or in police custody at the time of eligibility screening. Previously randomized as a participant in the study. Planned admission to a residential treatment facility or other formal SUD treatment program. Unwilling or unable to follow study procedures.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This is a double-blind, sham-controlled study.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: rTMS<br>Participants will receive up to 30 rTMS sessions within the 8-week treatment period. | Device: rTMS<br>* Each rTMS session will consist of 75 rTMS trains of 10 Hz for 4 seconds (40 pulses per train) with inter-train interval (ITI) of 11 seconds (a total of 3000 stimuli per session) over the left dorsolateral prefrontal cortex (DLPFC).<br>* Other names: TMS;|
| Sham Comparator: Sham (Placebo)<br>Participants will receive up to 30 sham rTMS sessions within the 8-week treatment period. | Device: Sham (Placebo)<br>* Each sham rTMS session will consist of 75 rTMS trains of 10 Hz for 4 seconds (40 pulses per train) with inter-train interval (ITI) of 11 seconds (a total of 3000 stimuli per session) over the left dorsolateral prefrontal cortex (DLPFC). In the placebo condition the magnetic field will be delivered in the opposite direction (away from the brain).<br>* Other names: Sham Repetitive Transcranial Magnetic Stimulation;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of participants who receive at least 20 sessions of rTMS/sham over the treatment period. | Treatment session attendance and completion will be tracked over the course of the study, and this record will constitute the primary feasibility outcome. | From first treatment session (Week 1, first study visit) to end of treatment at 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent of negative UDS from weekly UDS | A negative UDS for participants with cocaine as primary substance would be a UDS absent of cocaine; a negative UDS for participants with methamphetamine as primary substance would be a UDS absent of methamphetamine. | From first treatment week (Week 1) to end of treatment at 8 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Stimulant, Cocaine, Methamphetamine, Repetitive Transcranial Magnetic Stimulation, rTMS