Treating Stimulant Addiction With Repetitive Transcranial Magnetic Stimulation

Study Overview
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Brief Summary
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The purpose of this study is to establish a new treatment (repetitive transcranial stimulation (rTMS)) for Veterans with stimulant use disorder (SUD). Despite the large public health burden imposed by SUD, there is currently no FDA-approved or widely recognized effective somatic treatment. rTMS may be a promising treatment option for SUD. In this study, we will demonstrate the feasibility of applying rTMS to Veterans with SUD, examine the efficacy of rTMS in the treatment of SUD, and explore biomarkers that may guide patient selection for rTMS treatment and predict treatment response.

Official Title
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Treating Stimulant Addiction With Repetitive Transcranial Magnetic Stimulation

Conditions
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Stimulant Use Disorder, Substance-related Disorders

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: SCID confirmed diagnosis of SUD, severe Last use of stimulants >1 and <6 weeks Stable medication regimen (no change in dose or agents between 2 weeks prior to the start of and throughout the treatment phase of the study) Stable social environment and housing to enable regular attendance at clinic visits. Ability to undergo cognitive testing, fMRI scans, and rTMS (no contraindications) IQ > 80 Stable medical health Veteran at Palo Alto VA's Addiction Treatment Services Exclusion Criteria: Pregnant or lactating female History of prior adverse reaction to TMS On medications thought to significantly lower seizure threshold, e.g.: clozapine chlorpromazine clomipramine bupropion > 400 mg/day Use of direct dopaminergic antagonists or agonists History of seizures or conditions known to substantially increase risk for seizures Implants or medical devices incompatible with TMS Acute or unstable chronic medical illness that would affect participation or compliance with study procedures, e.g. unstable angina Unstable psychiatric symptoms that precludes consistent participation in the study, e.g.: active current suicidal intent or plan severe psychosis Inability to undergo fMRI scan, e.g. claustrophobia, presence of ferromagnetic objects in subject's body Other substance use disorder not in sustained remission Chronic or recurring Axis I psychiatric condition preceding SUD other than PTSD

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: Participants will be randomly assigned to one of two groups to receive active or sham rTMS.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Active rTMS<br>Receive active rTMS | Device: Repetitive transcranial magnetic stimulation (rTMS)<br>* rTMS is a non-invasive procedure in which administering a transient magnetic field induces electrical currents in specific, targeted brain regions. The intervention (active and sham) will be administered in 8 sessions across 2 weeks. The brain region targeted is the dorsolateral prefrontal cortex.<br>|
| Sham Comparator: Sham rTMS<br>Receive sham rTMS | Device: Repetitive transcranial magnetic stimulation (rTMS)<br>* rTMS is a non-invasive procedure in which administering a transient magnetic field induces electrical currents in specific, targeted brain regions. The intervention (active and sham) will be administered in 8 sessions across 2 weeks. The brain region targeted is the dorsolateral prefrontal cortex.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Relapse rate | Rate of stimulant use relapse and duration of abstinence compared between active vs. sham rTMS groups | 3 months after last rTMS treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Occupational/role functioning | Occupational/role functioning and changes in functioning compared between active vs. sham rTMS groups | Within 1 week before rTMS treatment, midpoint during rTMS treatment, within 1 week after rTMS treatment, and 3 months following rTMS treatment | 
| Rest/activity cycles | Actigraphy will be conducted to examine rest/activity cycles during and following rTMS treatment. Changes will be compared between active and sham rTMS groups, and correlated with improvements in SUD. | During 2-week rTMS treatment and for 1 month following treatment | 
| Reward circuit function and signaling | Before and after treatment, participants will undergo functional magnetic resonance imaging (fMRI) imaging while completing the Monetary Incentive Delay Task, a validated probe of reward processing circuit function and dysfunction. Signaling in the substantia nigra will be measured in an individual-subject, native space ROI approach as a marker of dopaminergic reward processing function, as well as in voxel-wise, whole-brain exploratory analyses. Changes in reward function and signaling will be compared between active vs. sham rTMS groups | Within 1 week before and after rTMS treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Magnetic resonance imaging, Dopamine, Reward processing, Transcranial magnetic stimulation