New Therapeutic Strategies for Inhibitory Control in Alcoholism

Study Overview
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Brief Summary
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This experimental research studies the efficacy of two different treatments for inhibitory control improvement in alcohol-dependent individuals, one consisting of Retrieval-Extinction Learning ( alcohol AAT Task) and the other consisting in rTMS of the right dorsolateral prefrontal cortex.

Detailed Description
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The main purpose of this study is to demonstrate the efficacy of two different treatments for inhibitory control improvement (measured by the modified Stop signal task): a behavioral treatment based on Retrieval-Extinction Learning, through the AAT (Alcohol Approach Avoiding Task) and a treatment based on the neuromodulation of prefrontal cortex through the rTMS (repetitive transcraneal magnetic stimulation) technique. To carry out this study, 105 alcoholic patients will be compared for clinical variables (abstinence/relapses), self-informed (UPPS) and behvavioral impulsivity (Stop signal task), along with biological measures for polymorphism determinations. Alcohol-dependent individuals will be divided into 4 groups of study (1:1 proportion for Retrieval-Extinction Learning with AAT and 2:1 (double for the effective technique comparing to placebo/control) for rTMS): Group 1 (N=30): exposure to an alcohol-related video followed by AAT; Group 2 (N=30): neutral-content video followed by AAT; Group 4 (30): active stimulation rTMS (10 Hz) ; Group 4 (N=15): placebo stimulation SAM.

Official Title
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New Therapeutic Strategies for Inhibitory Control Improvement of Alcohol-dependent Patients

Conditions
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Alcoholism

Intervention / Treatment
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* Behavioral: Retrieval-Extinction Learning
* Other: rTMS
* Other: SAM


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men and women aged between 18 and 50 years old. A minimum of 28 days of abstinence Consent to participate in the study. Exclusion Criteria: Subjects with other substance dependence ( with the exception of tobacco) Subjects with a history of brain injury or neurological diseases Denial for study participation Non-spanish speakers rTMS selected participants with be assed in order to discard epilepsy, presence for metallic elements and CNS valves

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 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
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Exposure<br>Exposure to a 5 minutes video related to alcohol consumption (updating/retrieval), followed by 10 minutes of the alcohol- AAT(Approach Avoidance Task) (extinction), during 4 days of training (2 weeks). | Behavioral: Retrieval-Extinction Learning<br>* The intervention consists of the accomplishment of the task of approach-avoidance of alcohol during 4 days of training. Subjects are instructed to respond with an approach movement (pulling a lever) to neutral images and to respond with avoidance movement (pushing the lever) to images of alcohol.<br>|
| Active Comparator: No exposure<br>Exposure to a 5 minutes video with neutral content (no retrieval) followed by 10 minutes of the alcohol- AAT (Approach Avoidance Task) , during 4 days of training. | Behavioral: Retrieval-Extinction Learning<br>* The intervention consists of the accomplishment of the task of approach-avoidance of alcohol during 4 days of training. Subjects are instructed to respond with an approach movement (pulling a lever) to neutral images and to respond with avoidance movement (pushing the lever) to images of alcohol.<br>|
| Experimental: Active rTMS<br>Each session (5 sessions along 2 weeks), patients receive active stimulation with repetitive transcraneal magnetic stimulation (rTMS) of the right dorsolateral prefrontal cortex. | Other: rTMS<br>* Previous to rTMS completion, MRI scans were performed in order to determinate the motor threshold trough 1Hz stimuli and locate the desired area with the neuronavigator. Motor threshold is defined as the stimulus with less intensity, able to generate a motor potential of at least 50 µV in 10 trials. Next, patients were called for 5 times per week, along 2 weeks, for receiving brain stimulation with Magstim Rapid coil. rTMS is performed at 10 Hz, during 4.9 seconds,for each set of stimuli (20), with a interval between sets of 30 seconds.<br>|
| Sham Comparator: SAM<br>Pacients receiving a sham stimulation (SAM), with a similar procedure to the experimental condition | Other: SAM<br>* Previous to rTMS completion, MRI scans were performed in order to determinate the motor threshold trough 1Hz stimuli and locate the desired area with the neuronavigator. Motor threshold is defined as the stimulus with less intensity, able to generate a motor potential of at least 50 µV in 10 trials. Next, patients were called for 5 times per week, along 2 weeks, for receiving brain stimulation with SAM coil.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Relapses | Number of relapses | 3 months | 
| Heavy drinking | Number of days of heavy drinking | 3 months | 
| Abstinence | Days of accumulated abstinence | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Behavioral Impulsivity | Stop signal task reaction times | 2 days | 
| Self-reported Impulsivity | scores for UPPS | 2 days | 
| Polymorphism distribution of CRH and ANK3 genes | Biological determinations-lymphocyte samples | 2 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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rTMS, AAT, Alcohol-Dependence, Relapses