Placebo-controlled Randomized Clinical Trial: tDCS to Prevent Relapse in Alcohol Use Disorder
Phase: NA
Conditions: Active tDCS, Sham tDCS
Sponsor: Brugmann University Hospital

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Placebo-controlled Randomized Clinical Trial: tDCS to Prevent 
Relapse in Alcohol Use Disorder 
NCT ID: not yet assigned 
Date: 25 February 2021 
 
 
 
1. Background 
Despite the available treatments in place, patients with alcohol use disorder (AUD) continue to 
relapse after treatment (Manning et al., 2016, 2020; Noël et al., 2021). For the past twenty years, 
neuromodulations techniques and their mechanisms, including transcranial direct current 
stimulation (tDCS), have been largely investigated in medical research (Ekhtiari et al., 2019; 
Fertonani & Miniussi, 2017; Nitsche et al., 2003; Philip et al., 2017). The tDCS is a 
neuromodulation tool acting by a current of maximum 2 mA delivered by two electrodes: the 
anode increases the cortical excitability (depolarizing the membrane potential on neurons) while 
the cathode inhibits the cortical excitability (hyperpolarizing the membrane potential)  (Zhao et 
al., 2017).  
The tDCS has shown interesting effects in patients with AUD when applied to the dorsolateral 
prefrontal cortex (dlPFC). The dlPFC is involved in decision-making, inhibitory control and 
working memory (Bechara 2005), as well as attentional bias (Bechara 2005), as well as attentional 
bias (Knight et al., 2020). The dlPFC appears to be hypoactivated in patients with AUD, which 
translates in impaired inhibition control and impaired attention to alcohol-related stimuli 
(Goldstein & Volkow, 2011).  
Currently in the scientific literature we can find many studies focusing on craving but only few 
investigating relapse’s mechanisms and treatment (Coles et al., 2018; Trojak et al., 2017). 
Nevertheless, two studies have shown that 10 sessions of tDCS on dlPFC (2mA, anode on the 
right, cathode on the left) allow a decrease in relapse’s rate (3 and 6 months after the intervention)  
(Klauss et al., 2014, 2018). Among a sample of 33 hospitalized patients, eight patients in the active 

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tDCS condition were still abstinent after 6 months follow-up, compared to two in the sham tDCS 
condition (50% versus 11.8% of the respective samples). 
Meta-analyses have shown a moderate effect of tDCS reducing craving (Chen et al., 2020; Hone-
Blanchet et al., 2015; Jansen et al., 2013; Kang et al., 2019; Luigjes et al., 2018; Mostafavi et al., 
2020; Sauvaget et al., 2015). The latest recommendations are to place the anode on the right 
CPFDL and the cathode on the left CPFDL, for a minimum of 5 sessions of 20 minutes at 2 mA 
(Fregni et al., 2020; Lefaucheur et al., 2017).  
We conducted a first clinical trial at Unit 72 Addictology of CHU Brugmann between 2017 and 
2020 (reference: CE 2017/117), which was funded by the King Baudouin Foundation (ref: 2016-
J1130650-206500) and then by the Brugmann Foundation (fund 2020-2021) (article in writing, 
pre-registered: https://clinicaltrials.gov/ct2/show/NCT03447054). The study had a design with 
2x2 conditions combining 5 sessions of (A) tDCS on the dlPFC (anode on the right and cathode 
on the left, active 2mA vs sham 0mA) simultaneously to (B) an inhibition cognitive training (ICT) 
type Go/Nogo (specific vs non-specific). The specific ICT consisted to associate the Nogo with 
alcohol images and Go with sports images. There were also neutral images associated with 50% 
of Go. While non-specific training had only neutral images. Results showed a decrease in 
relapse’s rate two weeks after treatment due to real tDCS combined with ICT. Moreover, we 
found out that real tDCS combined with specific ICT was more effective than real tDCS 
combined nonspecific ICT. Nevertheless, we did not find any significant effect on other clinical 
variables [craving (visual analog scale), symptoms of depression (BDI-II), anxiety (STAI-A), work 
memory (OSPAN) and inhibition (Stop signal task)]. 
Following these results, one questions still remains: Should tDCS be combined with ICT in order 
to be effective? To answer this question, we are conducting a new clinical trial with 5 sessions of 
tDCS on CPFDL (20minutes, anode on the right, left cathode) without an ICT. This study 
follows the same tDCS configuration as the previous one and takes place within the same 
multidisciplinary framework of treatment in order to compare our data. 
 
2. HYPOTHESES 
For patients with AUD, the intervention of five sessions of tDCS during a detoxification: 
- 
decreases the relapse rate 2 weeks after the treatment; 
- 
decreases patient craving; 
- 
improves depression and anxiety; 
- 
strengthens inhibitory capacities. 

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3. PROTOCOL 
3.1. Patients 
This is a clinical trial that is part of an alcohol detoxification cure at Unit 72 Addictology of 
CHU Brugmann. The idea is to add a neuromodulation intervention to the initial management, 
multidisciplinary and psycho-bio-social. This will be a randomized, sham-controlled, single-
blind study. 
A total of 60 subjects will be recruited according to the inclusion and exclusion criteria. They 
will be randomly divided into two groups: the ‘active’ group (A) that will benefit from tDCS 
stimulation and the ‘sham’ group (S). 
Exclusion criteria: 
- 
Personal history of epilepsy; 
- 
Have metal head implants that counter-indicate electrical stimulation;  
- 
Diagnosis of chronic psychotic disorder, schizophrenia or bipolar type 1 disorder; 
- 
Use of alcohol or other illicit substances during the experiment; 
- 
Hair incompatible with neuromodulation. 
 
 
3.2. Procedure  
During the first two weeks of hospitalization, the study will be offered to patients. If they accept, 
a first semi-structured interview will be organized to explain the study, sign the informed consent, 
collect more information and verify the inclusion and exclusion criteria. During this interview, 
the demographic characteristics (age, sex and level of education), history with alcohol (number of 
years of dependence, number of previous treatment, etc.), frequency and amount of alcohol 
consumed before treatment, psychiatric history, etc. The DSM 5 criteria will be verified, and 
patients will complete these questionnaires in French version: Alcohol Use Disorder 
Identification Test (AUDIT), Impulsivity Behavior Scale (UPPS-P) and Trait Anxiety Inventory 
(STAI-B). 
From Monday to Friday of the third week of hospitalization, patients will receive the 
procedure. Five consecutive 20 minute days of tDCS, either active or sham. Before and after 
each session, the tie will be measured using analog visual scales. To measure the effects of 
tDCS, on the Friday preceding (T1) and the Monday following (T2) the intervention week, 

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patients will respond to a battery of questionnaires and cognitive tasks during the recording of 
evoked potentials (via an electroencephalogram). T1 and T2 will each last approximately one 
hour.  
Figure 1: Study plan. Day 1 is theoretically the first day of hospitalization and the procedure takes 
place between Day 15 and 19. 
 
 
In order to observe whether specific neural changes underlie relapse and abstinence, evoked 
potentials will be acquired for each participant at two points, before the start of the stimulation by 
tDCS and once the five sessions have been completed.  
Once hospitalization is complete, patients will be followed by telephone call to find out the status 
of their abstinence and/or alcohol consumption. The call will be made via Unit 72 personnel. 
Recruitment would start if possible at the end of March 2021 for a period of 12 months. Based 
on our estimates based on the performance of the previous study, five patients will be recruited 
per month. 

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3.3. tDCS 
During the neuromodulation session, the patient will watch nature documentaries, cut into 5 
episodes of 20 minutes. 
The configuration of tDCS is based on recommendations in the literature (Fregni et al., 2020; 
Lefaucheur et al., 2017). 
- 
5 sessions of bilateral stimulation of the dlPFC; 
- 
Electrode setup: the anode right on F4 and cathode left on F3, according to international 
system 10-20 for EEG; 
- 
Administration of 2mA of current for 20 min; 
- 
Sham group: 0 mA for 20 min, 2 mA for the first 15 and last seconds. 
 
Figure 2: Localization of the anode (red) and the cathode (blue) over the dlPFC. 
 
 
3.4. Measures 
Primary dependent variables : 
Relapse and total abstinence measured at several defined times: two weeks, one month, three 
months, six months and one year after treatment.. 
Secondary dependent variables: 
 Craving measured before and after each tDCS session via visual analog scales, such as 
Likert -100 to +100, as well as the Alcohol Urge Questionnaire (AUQ) with 8 items. 
Craving will also be measured in T1 and T2 through the Craving Experience 
Questionnaire (CEQ); 

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 Symptoms of depression with the Beck Depression Inventory (BDI-II) and positive and 
negative affectivity with the Positive and Negative Affect Schedule (PANAS) measured at 
T1 and T2; 
 Anxiety trait in T1 and T2 with the State Anxiety Inventory (STAI-A). 
 The working memory performance measured in T1 and T2 with the span reversed. 
 Inhibitory control evaluated by performance at a Go/Nogo task and its event-related 
potential (Nogo N2 and Nogo P3). This measurement will be carried out as part of a 
clinical 
examination 
(cognitive 
and 
neurophysiological 
battery 
with 
an 
electroencephalogram) offered to patients during their hospitalization at Unit 72. This 
review will be conducted before and after the intervention (in T1 and T2). 
All the questionnaires were in French version. 
Metacognition items: 
At the end of the experiment, patients will be asked orally (1) Do you think you are in the active 
tDCS group?, (2) Would you be interested in continuing this intervention over a longer period 
of time? 
 
3.5. Statistical analyses 
Primary measurement: In order to respond to our primary assumptions about relapse, we will 
perform logistic regressions with the independent variable conditions (tDCS active scored 1 and 
tDCS sham scored -1) and the variable dependent relapse at each measurement (2 weeks, 1 
month, 3 months, 6 months and 1 year). A Kaplan-Meier survival analysis will be performed on 
the number of days prior to relapse to compare the curves up to one year of follow-up. 
Finally, in order to compare our two conditions to the four conditions of the previous study, we 
will perform a logistic regression with linear polynomial contrasts (combined active tDCS with 
ICT > tDCS only > tDCS sham). 
 
Secondary measures: In order to respond to our secondary assumptions about the variables 
before and after the intervention, we will perform mixed repeated measures ANOVAs [Time 
(T1 vs. T2) x Condition (tDCS active vs. tDCS sham)]. 
 
 

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4. Benefices 
At the individual level, stimulation by tDCS could on the one hand help patients to prolong 
alcohol abstinence time and on the other have positive effects on mood, especially an 
improvement in the level of anxiety and depression. 
In a broader sense, this study will contribute to a better definition of the mechanisms involved in 
abstinence and in the phenomenon of relapse of alcohol use disorders. It will also compare 
whether tDCS is more effective alone or combined with cognitive training. The purpose of this 
study is to support medical research to improve management for people with alcohol 
dependence. 
 
5. Safety and tolerability of tDCS 
The tolerance of tDCS will be assessed during stimulation with an likert scale. A short 
questionnaire reporting possible side effects will be distributed to all participants to record the 
symptoms caused by stimulation. 
The most common side effects include tingling, itching, and mild erythema. Although they are 
less frequent, the perception of a feeling of discomfort or burning, as well as the occurrence of a 
headache, are also possible events. These are side effects that are well tolerated, essentially limited 
to the time of stimulation and do not require medical treatment. Severe adverse effects or late 
onset were not identified. 
 
6. Ethics 
This study will be carried out in accordance with the ethical principles set out in the Declaration 
of Helsinki (1964) and the Belgian law of 7 May 2004 on experiments on the human person. The 
signature of a free and informed written consent will be requested from the selected participants 
prior to commencing the experiment. 
 
 
 
 

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Appendices: 
 
Table 1: Lists of documents / questionnaires / tasks that will be collected 
 
Semi-structured interview 
Day 3-4 
T1 
Day 12 
Sessions 
Day 15-19 
T2 
Day 22 
Informative letter 
X 
 
 
 
Informed consent 
X 
 
 
 
Anamnesis 
X 
 
 
 
AUDIT (AUD symptoms) 
X 
 
 
 
Craving Experience Questionnaire 
X 
 
 
 
UPPS-P (impulsivity) 
X 
 
 
 
STAI-B (trait anxiety) 
X 
 
 
 
STAI-A (state anxiety) 
 
X 
 
X 
Visual analog scales on craving 
 
X 
X 
X 
Alcohol Urge Questionnaire 
 
X 
 
X 
PANAS 
 
X 
 
X 
BDI-II 
 
X 
 
X 
Reverse memory span 
 
X 
 
X 
Go/Nogo with ERPs 
 
X 
 
X 
Questions on metacognition 
 
 
 
X