A Combined Neurofeedback-TMS Intervention for Alcohol Use Disorder

Study Overview
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Brief Summary
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The goal of this clinical study is to test the effectiveness of a supplemental fMRI neurofeedback and/or TMS intervention in individuals seeking treatment for Alcohol Use Disorder. After an initial visit, participants will come in once a week for four (4) weeks for an intervention session, which may or may not include TMS and MRI. Participants will be contacted for monthly follow-ups (remotely) for up to 12 months and will be asked to come in for two MRI follow-ups at 6 and 12 months.

Official Title
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A Combined Neurofeedback-TMS Intervention for Alcohol Use Disorder

Conditions
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Alcohol Use Disorder

Intervention / Treatment
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* Behavioral: Realtime fMRI Neurofeedback - Active
* Device: TMS - Active
* Behavioral: Realtime fMRI Neurofeedback - Yoked Sham
* Device: TMS - Sham


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 19-65 Receiving treatment for Alcohol Use Disorder Exclusion Criteria: MRI Contraindications Presence of metal in the body that would make having a 7T MRI unsafe (including facial tattoos) Claustrophobia, such that individual would be unable to stay in the MRI for up to 1 hr Hearing loss, including tinnitus, that might be made worse by MRI or TMS TMS Contraindications Has ever had a seizure, or has a family history of epilepsy Taking medications or substances that lower the seizure threshold Implanted devices that are in the head or rely on physiological signals History of neurological disease, such as stroke or brain tumor Head injury with loss of consciousness greater than 30 minutes Actively withdrawing from alcohol Family history of schizophrenia or presence of psychotic symptoms

Ages Eligible for Study
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Minimum Age: 19 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: Factorial Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Neurofeedback-active + TMS-active<br>4 sessions of: TMS (protocol: 10 Hz pulses delivered at 110% of MT in 60 x 5 sec trains with 25 sec ITI) Neurofeedback (protocol: presentation of own brain activity from multiple ROIs measured using fMRI) | Behavioral: Realtime fMRI Neurofeedback - Active<br>* fMRI aided reinforcement of craving regulation<br>Device: TMS - Active<br>* rTMS to right dorsolateral prefrontal cortex to reduce craving<br>* Other names: Magventure Magpro;|
| Active Comparator: Neurofeedback-active + TMS-sham<br>4 sessions of: TMS (protocol: 10 Hz pulses delivered using the Sham TMS coil in 60 x 5 sec trains with 25 sec ITI) Neurofeedback (protocol: presentation of own brain activity from multiple ROIs measured using fMRI) | Behavioral: Realtime fMRI Neurofeedback - Active<br>* fMRI aided reinforcement of craving regulation<br>Device: TMS - Sham<br>* rTMS using placebo coil (no brain stimulation, emulates other features of active TMS), placed over right dorsolateral prefrontal cortex<br>|
| Active Comparator: Neurofeedback-sham + TMS-active<br>4 sessions of: TMS (protocol: 10 Hz pulses delivered at 110% of MT in 60 x 5 sec trains with 25 sec ITI) Neurofeedback (protocol: presentation of other's brain activity from multiple ROIs measured using fMRI) | Device: TMS - Active<br>* rTMS to right dorsolateral prefrontal cortex to reduce craving<br>* Other names: Magventure Magpro;Behavioral: Realtime fMRI Neurofeedback - Yoked Sham<br>* Display of feedback from other participant's sessions to serve as a sham for fMRI aided reinforcement of craving regulation<br>|
| Sham Comparator: Neurofeedback-sham + TMS-sham<br>4 sessions of: TMS (protocol: 10 Hz pulses delivered using the Sham TMS coil in 60 x 5 sec trains with 25 sec ITI) Neurofeedback (protocol: presentation of other's brain activity from multiple ROIs measured using fMRI) | Behavioral: Realtime fMRI Neurofeedback - Yoked Sham<br>* Display of feedback from other participant's sessions to serve as a sham for fMRI aided reinforcement of craving regulation<br>Device: TMS - Sham<br>* rTMS using placebo coil (no brain stimulation, emulates other features of active TMS), placed over right dorsolateral prefrontal cortex<br>|
| No Intervention: Check-In Only<br>4 sessions of: Completing typical pre-TMS/MRI procedures Being prompted to reflect on outside treatment (TAU) | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Alcohol Use over Time | Alcohol Timeline Followback (alc-TLFB) | Assessed at weeks: 1 (baseline), 2-5 (intervention sessions, pre and post), 9, 13, 17, 21, 25, 33, 37, 41, 45, 49, 53 (follow-ups) | 
| Change in Alcohol Craving over Time | Alcohol Craving Questionnaire (ACQ) | Assessed at weeks: 1 (baseline), 2-5 (intervention sessions, pre and post), 9, 13, 17, 21, 25, 33, 37, 41, 45, 49, 53 (follow-ups) | 
| Change in Community Functioning over Time | Drinker Inventory of Consequences (DrInC) | Assessed at weeks: 1 (baseline), 2-5 (intervention sessions), 9, 13, 17, 21, 25, 33, 37, 41, 45, 49, 53 (follow-ups) | 
| Change in Employment Status over Time | self-reported employment status | Assessed at weeks: 1 (baseline), 2-5 (intervention sessions), 9, 13, 17, 21, 25, 33, 37, 41, 45, 49, 53 (follow-ups) | 
| Change in Aggression and Victimization over Time | Revised Conflict Tactics Scales (CTS-R) | Assessed at weeks: 1 (baseline), 2-5 (intervention sessions), 9, 13, 17, 21, 25, 29, 33, 37, 41, 45, 49, 53, 57 (follow-ups) | 
| Change in Antisocial Behavior over Time | number of self-reported contacts with the police, convictions, and other criminal behaviors | Assessed at weeks: 1 (baseline), 2-5 (intervention sessions), 9, 13, 17, 21, 25, 29, 33, 37, 41, 45, 49, 53, 57 (follow-ups) | 
| Change in Brain Activity during Alcohol Cue Presentation over Time | Measured via fMRI; standard alcohol cue reactivity | Assessed at weeks: 1 (baseline), 5 (post final intervention), 29 and 57 (follow-ups) | 
| Change in Brain Activity during Simultaneous Sociomoral & Alcohol Cue Presentation over Time | Measured via fMRI; alcohol-cued sociomoral processing | Assessed at weeks: 1 (baseline), 5 (post final intervention), 29 and 57 (follow-ups) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Brain Gray Matter Structure over Time | Measured via MRI; gray matter volume | Weeks: 1 (baseline), 5 (post final intervention), 29 and 57 (follow-ups) | 
| Change in Brain White Matter Structure over Time | Measured via MRI; white matter diffusion | Weeks: 1 (baseline), 5 (post final intervention), 29 and 57 (follow-ups) | 
| Change in Resting State Functional Connectivity over Time | Measured via fMRI | Weeks: 1 (baseline), 5 (post final intervention), 29 and 57 (follow-ups) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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TMS, treatment seeking, alcohol, neurofeedback, supplemental intervention, heavy drinking, problems with drinking