Clinical trial NCT05471154: Non-invasive Brain Stimulation of the Prefrontal Cortex in Substance Use Disorders
Official title: Non-invasive Brain Stimulation of the Prefrontal Cortex in Substance Use Disorders
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Alcohol Use Disorder (AUD)
Keywords: AUD
SUD
tDCS
NIBS
craving
abstinence
EEG
Lead sponsor: Universitair Ziekenhuis Brussel
Sponsor class: OTHER
First posted: 2022-07-22
Enrollment: 70
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: In this study, High-Definition transcranial direct current stimulation is used as treatment/intervention (HD-tDCS). HD-tDCS will be applied with a current of 2 mA during 20 minutes. Participants are semi-randomly assigned to the two experimental groups (active stimulation vs. sham) by the coordinating researcher, taking into account the sex of the participant. The sham condition will use the same montage but stop stimulation after a short ramp-up of 1 minute).
Primary purpose: TREATMENT

Brief summary: Every year, alcohol causes 3 million deaths worldwide. Even though a lot of treatments already exist, many of them are characterized by a high percentage of drop-out or relapse. Transcranial direct current stimulation (tDCS), a NIBS, is receiving increased attention as a possible new addiction treatment. However, little consensus exists in the concrete parameters (e.g. montage, current, intensity). Moreover, a lot of tDCS research focuses on subjective outcomes, like the report of craving, which are more prone to different biases and fluctuations. In this study, we aim to investigate the effect of HD-tDCS, a more focal stimulation variant, on AUDs. Using this intervention, stimulation can be restricted to one hemisphere, controlling for possible inhibition effects of the cathode. A between-subject design will be carried out, including patients with an AUD. Participants will receive 5 sessions of either real or sham right anodal HD-tDCS over the dorsolateral prefrontal cortex (dlPFC). Craving will be accounted for at baseline and after every stimulation session. Moreover, we will measure the activity of the brain in rest and during two inhibition tasks (Go/NoGo and cue reactivity task). This objective measure will be carried out both before (baseline) and at two time points after the stimulation, to measure effects on both the short and longer term. One month after the intervention, abstinence will be checked through a follow-up phone call. Through this study, we aim to describe positive effects of right dlPFC stimulation on craving, abstinence, and EEG measures.

Detailed description: Population

This study will focus on patients with AUD, as these are the easiest to recruit. Participants in this study will be enrolled in a residential SUD treatment or a day hospital SUD treatment. As such, medical supervision can be guaranteed. In addition, sobriety is assessed objectively and routinely as part of TAU, enabling exclusion of patients under influence of alcohol. Cognitive impairment will be assessed using the MoCA and participants with a score below 10 (severe cognitive impairment) will be excluded.

Design

This study will use a between-subjects design. The experiment will be conducted double-blind to minimalize placebo effects and researcher bias. Group allocation will be conducted semi-randomly, with matching of participants' sex. The otherwise identical placebo protocol features sham stimulation (after a short ramp up, current drops again). The short ramp up is used to induce the same sensations as in the stimulation group (possible itching and tingling).

Measures

Self-report

Self-report measures will be collected prior to the intervention to discern endophenotypes predicting treatment response. The Behavioral Inhibition/Behavioral Activation System (BIS/BAS), Effortful Control Scales, Barrat Impulsiveness Scale and the Alcohol Use Disorders Identification Test (AUDIT) are collected. The Beck Depression Inventory (BDI) will be collected both before and after intervention.

Cognitive screening

The Montreal Cognitive Assessment (MoCA) will be used to exclude patients with severe cognitive impairment. Participants with a score of 10 or lower on the MoCA will be excluded from the study.

Medication regime

The medication regime of the participants will be registered, since medication may influence tDCS effects.

Resting state EEG

A resting state EEG is collected before the intervention as well as immediately after the first stimulation session and after the last stimulation session. These timepoints are used to collect data concerning the effect of tDCS on both short term and longer term.

ERPs and behavioral measures

Apart from resting state, event related potentials (ERP's) will be collected at the same time points, during different behavioral tasks: a cue reactivity task reflecting activation of the reward system and a Go-NoGo task reflecting executive functions, more concrete response inhibition.

* Cue-reactivity task: In this task, participants will be requested to indicate the occurrence of any infrequent stimulus by pressing the response button as fast as possible. Participants will be shown successions of pictures of a person drinking water (frequent), alcohol (infrequent) or soft drinks (equally infrequent). All stimuli will be presented in a random order. Three different alcohol-related pictures will be used, selected during the screening for alcohol preference.
* Go/NoGo task: In this task, participants have to press a button as fast as possible, whenever the Go stimulus (the letter M) is displayed. When another, infrequent stimulus is displayed (NoGo, the letter W), they have to refrain from pressing the button. The letters are superimposed on an alcohol-related picture or a non-alcohol related picture.

In both tasks, trials followed by incorrect responses will be eliminated from the data set. Reaction times and percentage of errors will be registered as behavioral measures.

Safety and blinding

After every session of HD-tDCS adverse effects will be assessed. Moreover, participants will systematically be asked whether they believe to have received real or placebo stimulation in the past session.

Subjective craving

A subjective craving measure will be carried out before the intervention and after every stimulation session.

Follow-up

1 month after the last stimulation session, verbally self-reported abstinence status will be registered. To do so, the Quick Drinking Screen (QDS) will be used.

Intervention

5 sessions of 2mA HD-tDCS (active or sham) will be used as intervention during 20 minutes.

Eligibility criteria: Inclusion Criteria:

* DSM-V criteria for alohol use disorder
* dutch speaking
* 18-65 years old
* abstinence in the past 10 days

Exclusion Criteria:

* diagnosis or family history of epilepsy
* a history of severe brain injury
* a cardiac pacemaker or electronic implants
* migraine
* a scalp skin condition
* pregnancy
* concurrent treatment with benzodiazepines
* hairstyle incompatible with EEG-measurements
* a psychotic disorder or neurological disease
* severe cognitive impairment defined as a score lower than 10 on the Montreal Cognitive Assessment (MoCA).

Primary outcomes:
measure: Abstinence
timeFrame: 1 month after the intervention
Secondary outcomes:
measure: ERP measures
timeFrame: Total estimated period of one week: pre-intervention (on day 1;T1), after a first stimulation session (day 1, 30 minutes after T1) and after the full intervention of 5 sessions (on day 5,4 days after T1)
measure: Craving measures
timeFrame: Total estimated period of one week: measure pre-intervention (day 1, T1) and after every stimulation session (T1 + 1 hour, T1 + 1 day, T1 + 2 days, T1 + 3 days and T1+ 4 days)
measure: Effortful control scale (EC)
timeFrame: The week before first day of intervention (T1), during a block of questionnaires (estimated at 1 hour in time spending)
measure: resting state EEG in alpha band
timeFrame: otal estimated period of one week: pre-intervention (on day 1;T1), after a first stimulation session (day 1, 30 minutes after T1) and after the full intervention of 5 sessions (on day 5,4 days after T1)
measure: Behavioral inhibition system/behavioral approach system (BIS/BAS) Scale
timeFrame: The week before first day of intervention (T1), during a block of questionnaires (estimated at 1 hour in time spending)
measure: Barratt Impulsivity Scale (BIS)
timeFrame: The week before first day of intervention (T1), during a block of questionnaires (estimated at 1 hour in time spending)
measure: Montreal Cognitive Assessment (MoCA)
timeFrame: The week before first day of intervention (T1), during a block of questionnaires (estimated at 1 hour in time spending)
measure: screening alcohol preference
timeFrame: The week before first day of intervention (T1), during a block of questionnaires (estimated at 1 hour in time spending)
measure: Alcohol Use Disorders Identification Test (AUDIT)
timeFrame: The week before first day of intervention (T1), during a block of questionnaires (estimated at 1 hour in time spending)
measure: Beck Depression Inventory (BDI)
timeFrame: The week before first day of intervention (T1) and after intervention (T2)
Other outcomes:
Locations:
city: Boechout
country: Belgium
facility: Multiversum
state: Antwerpen
Study officials:
affiliation: Vrije Universiteit Brussel
name: Natacha Deroost, PhD
role: STUDY_CHAIR
affiliation: Vrije Universiteit Brussel
name: Kris Baetens, PhD
role: STUDY_DIRECTOR
affiliation: PC Multiversum Boechout
name: Geert Dom, MD
role: STUDY_CHAIR
affiliation: PC Multiversum Boechout
name: Marianne Destoop, MD
role: STUDY_CHAIR
References: