Severe Alcohol-use Disorder: a tDCS and Response Inhibition Training Intervention

Study Overview
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Brief Summary
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Most severe forms of alcohol-use disorder are thought to reflect an abnormal interplay between two neural systems: an overly active impulsive one driven by immediate rewards prospects and a weak reflective one, tuned on long-term prospects. The investigators propose that two non-pharmacological interventions, Transcranial Direct Current Stimulation (tDCS) and Inhibitory Control Techniques (ICT) may act on both systems when combined, which might ultimately result is a reduction of alcohol relapse rate.

Detailed Description
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Treating Alcohol dependence remains notoriously difficult despite use of several medications, psychotherapeutic and psychosocial interventions. Alcohol dependence is thought to reflect an abnormal interplay between two neural systems: an overly active impulsive one driven by immediate rewards prospects and a weak reflective one, tuned on long-term prospects. The investigators proposes that two non-pharmacological interventions, Transcranial Direct Current Stimulation (tDCS) and Inhibitory Control Techniques (ICT) may act on both systems when combined. tDCS has been found to improve working memory, which is necessary to evaluate long-term consequences of actions. ICT is able to modify the automatic approach tendencies towards appetitive cues. The investigators will recruit 160 alcohol-dependent patients and divide them randomly between four treatment conditions : real transcranial Direct Current Stimulation (tDCS) with active or control Inhibitory Control Technique (ICT ); or sham (placebo) tDCS with active or control ICT. Patients will be evaluated with primary outcome measures (alcohol consumption patterns) and secondary outcome measures (working memory and changes in alcohol-related stimuli affective values).

Official Title
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Treating Alcohol Dependence : Testing a Combined Treatment Model Using Transcranial Direct Current Stimulation (tDCS) and Inhibitory Control Training (ICT)

Conditions
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Alcohol Use Disorder

Intervention / Treatment
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* Behavioral: Combined TDCS active and ICT active
* Behavioral: Combined TDCS sham and ICT active
* Behavioral: Combined TDCS active and ICT inactive
* Behavioral: Combined Sham TDCS and inactive ICT


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with severe alcohol-use disorder (DSM-5 criteria), hospitalized for detoxification. Severity of alcohol use disorder must be at least moderate (at least 4 DSM-5 criteria) Aged between 18 and 65 years Comorbidity with anxiety disorders and depressive disorders is allowed Patients must be illegal drug free for 3 weeks at beginning of trial Pharmacotherapy: patients should be benzodiazepines free at the moment of inclusion. They are allowed to continue other psychotropic medication (antidepressants, antipsychotics, mood stabilizers), providing they are following a stable regimen that will not be changed during the protocol time. Patients must be reachable for follow-up Exclusion Criteria: Previous neurological conditions (epilepsy, traumatic brain injury, stroke) Present delirium, confusion or severe cognitive disorder Schizophrenia, chronic psychotic disorders, bipolar type 1 disorder. Any severe, life-threatening disorders High suicidal risk Specific contraindications for tDCS: metallic plates in the head Alcohol medication treatment initiated during the rehab: acamprosate, disulfiram, baclofen, nalmefen.

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: 2 (active, sham tDCS) x 2 (active, inactive response inhibition training) factorial design
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Combined TDCS active and ICT active<br>Five consecutive days: Twenty minutes of TDCS on the right dorsolateral prefrontal cortex while performing an alcohol-cue inhibitory control training consisting to systematically paired go responses with non-alcohol pictures and no-go responses with alcohol-related pictures. | Behavioral: Combined TDCS active and ICT active<br>* Five 20-minute long sessions including TDCS (2 MicroAmperes during 20 minutes) and ICT, 5 consecutive days<br>* Other names: Experimental;|
| Active Comparator: Combined TDCS sham and ICT active<br>Five consecutive days: Twenty minutes of sham TDCS on the right dorsolateral prefrontal cortex, while performing a no-cue go/no-go training consisting to carry out a go/no-go paradigm with no alcohol-related content. | Behavioral: Combined Sham TDCS and inactive ICT<br>* Five 20-minute long sessions including TDCS and no-cue inhibition training, 5 consecutive days<br>* Other names: Active/inactive;|
| Active Comparator: Combined TDCS active and ICT inactive<br>Five consecutive days: Twenty minutes of active TDCS in association with no-cue go/no-go training consisting to carry out a go/no-go paradigm with no alcohol-related content. | Behavioral: Combined TDCS active and ICT inactive<br>* Five 20-minute long sessions including TDCS sham and no-cue inhibition training, 5 consecutive days<br>* Other names: Sham/inactive;|
| Sham Comparator: Combined Sham TDCS and inactive ICT<br>Five consecutive days: Twenty minutes of Inactive TDCS combined with an non alcohol-cue inhibitory control training consisting to carry out a go/no-go paradigm with no alcohol-related content. | Behavioral: Combined TDCS sham and ICT active<br>* Five 20-minute long sessions including TDCS sham (non active) and ICT, 5 consecutive days<br>* Other names: Sham/active;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reduction of alcohol use in post-treatment at week 2 | Based on self-report questionnaires (grams of ethanol/occasion, per/day, number of consecutive days of alcohol drinking) | é weeks post-rehab | 
| Reduction of alcohol use in post-treatment at week 4 | Based on self-report questionnaires (grams of ethanol/occasion, per/day, number of consecutive days of alcohol drinking) | 4 weeks post-rehab | 
| Reduction of the relapse rate in post-treatment at week 2 | Based on self-report questionnaires and on one other significant person's feedback; binary outcome (relapser or non-relapser) | 2 weeks post-rehab | 
| Reduction of the relapse rate in post-treatment at week 4 | Based on self-report questionnaires and on one other significant person's feedback; binary outcome (relapser or non-relapser) | 4 weeks post-rehab | 
| Reduction of alcohol use in post-treatment at week 12 | Based on self-report questionnaires (grams of ethanol/occasion, per/day, number of consecutive days of alcohol drinking) | 12 weeks post-rehab | 
| Reduction of the relapse rate in post-treatment at week 12 | Based on self-report questionnaires and on one other significant person's feedback; binary outcome (relapser or non-relapser) | 12 weeks post-rehab | 
| Reduction of alcohol use in post-treatment at week 24 | Based on self-report questionnaires (grams of ethanol/occasion, per/day, number of consecutive days of alcohol drinking) | 24 weeks post-rehab | 
| Reduction of the relapse rate in post-treatment at week 24 | Based on self-report questionnaires and on one other significant person's feedback; binary outcome (relapser or non-relapser) | 24 weeks post-rehab | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cue reactivity (attractiveness) at day 22 | measures of attractiveness of used and novel alcohol-related pictures: Likert scale ranging from not (score of 0) at all to very much (score of 9) | at post-intervention (day 22 of hospitalization) | 
| Cue reactivity at day 22 | measures of attractiveness of used and novel alcohol-related pictures: Likert scale ranging from not (score of 0) at all to very much (score of 9) | at post-intervention (day 22 of hospitalization) | 
| Cue reactivity (valence) at day 22 | emotional content (valence) of pictures used in the response inhibition practice and of new pictures. Likert scale ranging from not (score of 0) at all to very much (score of 9) | at post-intervention (day 22 of hospitalization) | 
| Cue reactivity (arousal) at day 22 | emotional content (arousal) of pictures used in the response inhibition practice and of new pictures. Likert scale ranging from not (score of 0) at all to very much (score of 9) | at post-intervention (day 22 of hospitalization) | 
| Cue reactivity (alcohol verbal fluency) at day 12 | Alcohol verbal fluency (from Goldstein et al., 2007; Drug and Alcohol Dependence, 89:97-101 and Hon et al., 2016, Psychopharmacology, 233: 851-861: Participants are instructed to name as many alcohol-related words as possible in 1 min. Responses were audio recorded and independently coded into three categories: neutral, positive and negative valence by two researchers. | at baseline (day 12 of hospitalization) | 
| Cue reactivity (alcohol verbal fluency) at day 22 | Alcohol verbal fluency (from Goldstein et al., 2007; Drug and Alcohol Dependence, 89:97-101 and Hon et al., 2016, Psychopharmacology, 233: 851-861: Participants are instructed to name as many alcohol-related words as possible in 1 min. Responses were audio recorded and independently coded into three categories: neutral, positive and negative valence by two researchers. | at post-intervention (day 22 of hospitalization) | 
| response inhibition at day 12 | stop signal task (Logan, 1994): Stop Signal Reaction Time measure | at baseline (day 10 of hospitalization) | 
| response inhibition at day 22 | stop signal task (Logan, 1994): Stop Signal Reaction Time measure | at post-intervention (day 22 of hospitalization) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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relapse, craving, Alcohol, tDCS, inhibition, cognitive training, implicit cognition