aTBS for Treatment of Depression in AUD

Study Overview
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Brief Summary
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This study evaluates an accelerated schedule of theta-burst stimulation using a transcranial magnetic stimulation device for improvement of depressive symptoms and drinking behavior in individuals with alcohol dependence. In this open label study, all participants will receive accelerated theta-burst stimulation.

Detailed Description
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Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive procedure and an established technology. Research utilizing rTMS in patients with alcohol use disorder has shown some promising results. The limitations of this approach include the duration of the treatment (approximately 40 minutes per treatment session). Recently, researchers have aggressively pursued modifying the treatment parameters, such as using accelerated intermittent theta-burst stimulation (aiTBS), to reduce treatment times with possible enhanced efficacy with some preliminary success. This study intends to further modify the parameters to create a more rapid form of the treatment and look at the change in neuroimaging biomarkers.

Official Title
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Accelerated Theta Burst Stimulation for Treatment of Depression in Individuals With Detoxed Alcohol Use Disorder

Conditions
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Alcohol Use Disorder, Depression

Intervention / Treatment
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* Device: Accelerated theta burst treatment


Participation Criteria
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Eligibility Criteria
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Participant aged 18-65 years old with diagnosis of alcohol use disorder. Participant may also choose to or not to take pharmacotherapy during the study period. Participant has tried at least one medication in the past that has not helped the alcohol use disorder. If participants are taking medication, they must be on stable psychotropic medication or psychotherapy for at least 6 weeks prior to the study with plans to continue throughout study enrollment. Participant needs to be at least one week after last alcohol/ substance use and had the last drink within one year of the beginning of the study participation. Participant endorses depressive symptom(s), indicated by a MARDS score >= 20. All participants must be assigned to a psychiatrist and agree to continue to be assigned to a psychiatrist throughout study enrollment. Able to read, understand, and provide written, dated informed consent prior to screening. Participants will be deemed likely to comply with study protocol and communicate with study personnel about adverse events and other clinically important information.

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Accelerated theta burst treatment<br>All participants will receive theta-burst TMS. | Device: Accelerated theta burst treatment<br>* All participants will receive iTBS (intermittent theta burst stimulation) to the left DLPFC. The L-DLPFC will be targeted utilizing the Localite neuronavigation system. Stimulation intensity will be standardized at 80% of resting motor threshold adjust to the skull to cortical surface distance. Stimulation will be delivered to L-DLPFC using the MagPRo stimulator.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline Montgomery Asberg Depression Rating Scale (MADRS) | A ten item diagnostic questionnaire used to measure the severity of depressive episodes in patients with mood disorders. The MADRS uses a 0 to 6 severity scale, scored following the interview. Scoring/Interpretation: Higher scores indicate increasing depressive symptoms. ... Cut-off points include: 0 to 6 - symptom absent, 7 to 19 - mild depression, 30 to 34 - moderate, 35 to 60 - severe depression. | Baseline and immediate post-stimulation | 
| Change from baseline Montgomery Asberg Depression Rating Scale (MADRS) | A ten item diagnostic questionnaire used to measure the severity of depressive episodes in patients with mood disorders. The MADRS uses a 0 to 6 severity scale, scored following the interview. Scoring/Interpretation: Higher scores indicate increasing depressive symptoms. ... Cut-off points include: 0 to 6 - symptom absent, 7 to 19 - mild depression, 30 to 34 - moderate, 35 to 60 - severe depression. | Baseline and 1 month post-stimulation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in functional connectivity from baseline as measured by MR imaging | Pre- and post resting state functional connectivity and structural T1-weighted MRI scans to determine the anti-correlated LDLPFC and SCC treatment location. The identified cluster with the greatest anti-correlation between the LDLPFC and SCC will have been utilized for the targeted aiTBS treatment. This algorithm will have also been applied to the post-imaging sessions to give measurements of voxel-wise blood flow in this anti-correlation targeted brain ROI. | Baseline and immediate post-stimulation | 
| Change in functional connectivity from baseline as measured by MR imaging | Pre- and post resting state functional connectivity and structural T1-weighted MRI scans to determine the anti-correlated LDLPFC and SCC treatment location. The identified cluster with the greatest anti-correlation between the LDLPFC and SCC will have been utilized for the targeted aiTBS treatment. This algorithm will have also been applied to the post-imaging sessions to give measurements of voxel-wise blood flow in this anti-correlation targeted brain ROI. | Baseline and 1 month post-stimulation | 
| Change in alcohol craving and consumption measured by Obsessive Compulsive Drinking Scale (OCDS) | OCDS is a 14-question self-rate tool to measure obsessive thoughts about alcohol and compulsive use of alcohol. The minimum obtainable score is 0, while the maximum obtainable score is 56. Higher scores represent a worse outcome. | Baseline and immediate post-stimulation | 
| Change in alcohol craving and consumption measured by Obsessive Compulsive Drinking Scale (OCDS) | OCDS is a 14-question self-rate tool to measure obsessive thoughts about alcohol and compulsive use of alcohol. The minimum obtainable score is 0, while the maximum obtainable score is 56. Higher scores represent a worse outcome. | Baseline and 1 month post-stimulation | 
| Change in heart rate variability | Heart rate variability will be measured using a NeuroConn device which involves electrodes being placed on the chest to record heart rate. | At the beginning and end of each stimulation day | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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alcohol addiction, depression, TMS, transcranial magnetic stimulation, theta burst, alcohol use disorder