Clinical trial NCT04897295: Neurobiological Effects of Transcranial Direct Current Stimulation Treatment in Alcohol Use Disorder
Official title: Neurobiological Effects of Transcranial Direct Current Stimulation Treatment in Alcohol Use Disorder: a Sham-controlled Trial.
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Alcohol Use Disorder (AUD)
Alcohol Abuse
Alcohol Dependence
Alcohol-Related Disorders
Drug Abuse
Substance Use Disorders
Mental Disorder
Keywords: Alcohol Use Disorder
transcranial Direct Current Stimulation
Non-Invasive Brain Stimulation
Craving
Brain Derived Neurotrophic Factor
Pro-Brain Derived Neurotrophic Factor
Lead sponsor: ITAB - Institute for Advanced Biomedical Technologies
Sponsor class: OTHER
First posted: 2021-05-21
Enrollment: 30
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: double blind, randomized, sham-controlled with a 1:1 allocation into 2 parallel arms
Primary purpose: TREATMENT

Brief summary: Background: Alcohol Use Disorder (AUD) is a complex psychiatric disorder, involving several brain areas and neurocircuits. Transcranial Direct Current Stimulation (tDCS) allows to stimulate superficial areas of brain using a weak electrical current. Preliminary data suggest that tDCS may reduce alcohol craving and consumption.

Objectives: The main outcome is to test if tDCS can reduce alcohol craving and use and to assess the changes in BDNF and pro-BDNF levels. Secondary outcomes are the assessment of other psychiatric dimensions (mood, behavioral and cognitive alterations) associated with prolonged alcohol use.

Eligibility: Healthy, right-handed adults ages 18-65 who do have AUD (moderate to severe).

Design: This is a randomized, double-blind, sham-controlled study with three phases: 1) a tDCS intensive treatment phase; 2) follow-up with weekly tDCS stimulation; 3) follow-up without tDCS stimulation.

Participants will be screened with:

* Psychometric Scales
* Medical history
* Physical exam
* Urine tests and breathalyzer
* After being enrolled, baseline behavioral and laboratory data will be collected. In particular, participants will undergo:
* Psychometric Scales
* Venous blood sample (BDNF/proBDNF levels)

Participants will be randomized to real or sham tDCS arm. The stimulation will be delivered daily for five days during the first week (intensive treatment phase) and then weekly for 3 months (follow-up with stimulation). During this period patient will be tested with a behavioral and psychometric evaluation.Therefore, participants will receive 3 follow-up monthly visits without tDCS stimulation, in which behavioral and psychometric data will be collected.

Treatment includes:

* tDCS: The tDCS will be delivered with a stimulator connected to two sponge electrodes, soaked in a saline solution. The stimulation will be administered at a current intensity of approximately 1 mA, for the duration of 20 minutes. The anode will be placed on the right DLPFC, the cathode on the contralateral cortical area.
* BDNF/proBDNF levels: A venous blood sample will be collected before the first stimulation and after the last stimulation of the intensive-stimulation period (first week). The blood sample will be centrifuged within 20 minutes of sampling at 1000 × g for 15 minutes. Then, the serum will be aliquoted and stored at -80 ° C until analysis.
* Repeat of screening tests and questionnaires
* Urine toxicological screen and breathalyzer

Detailed description: Transcranial Direct Current Stimulation (tDCS) consists in the application on the scalp of electrodes (anode and cathode) delivering a direct current of low intensity that cannot be perceived by the stimulated subject. In recent years, tDCS stimulation has been increasingly used in psychiatric clinical research and in the addiction field. Although there are some studies showing the anti-craving action of tDCS in alcohol use disorder (AUD), there are some differences between the stimulation parameters used in these works. Furthermore, there is a lack in the international scientific literature of studies that have investigated the neurobiological basis of tDCS activity. This double-blind randomized sham-controlled trial consist in an intensive daily tDCS stimulation for the first week, then 3 months of follow up with tDCS stimulation (one tDCS stimulation/week) and then 3 months of follow up without tDCS stimulation. Psychometric evaluations will be performed at: baseline, end of the first week of stimulation, 2 weeks, 3 months, 6 months. A venous blood sample will be collected before the first stimulation and after the last stimulation of the intensive first week treatment. The primary outcome of the study is the evaluation of the short-term clinical efficacy of the application of tDCS in subjects with AUD, applying a anodal stimulation (1 mA) on the right Dorso-Lateral Prefrontal Cortex (DLPFC) for 20 minutes for 5 consecutive days. The results on some psychiatric psychometric scales (examine possible changes in mood, cognition and other psychiatric domains) will represent additional criteria. Another outcome is to assess the neuromodulation at the level of DLPFC evaluating the changes in serum levels of the brain-derived neurotrophic factor (BDNF) and its precursor (pro-BDNF). After screening and informed consent, participants will undergo active or sham tDCS for one week during the intensive treatment phase, and a maintenance intervention (twice a week for 3 months), during the tDCS follow-up phase. Following this phase, participants will be followed for further 3 months, during which no rTMS will be delivered but clinical and imaging data will be collected.

Procedure: The project consists of: Screening Visit (baseline), phase 1 (intensive treatment phase), phase 2 (3 months- tDCS follow-up), phase 3 (3 months follow-up without rTMS). In the screening visit, a clinical interview to assess the eligibility of participant (following the inclusion and exclusion criteria) will be performed. The signature of the informed consent and the baseline clinical and cognitive data will be acquired. In Phase 1, all participants will be randomized in the active or sham arm. Participants will receive 20 minutes of anodal right DLPFC stimulation for 5 consecutive days. The assessor will evaluate the acute effect of treatment on craving , consumption and on the psychometric variable considered at the end of this phase. A venous blood sample will be collected before the first stimulation and after the last stimulation of the intensive-stimulation period to asses the BDNF and pro-BDNF level. In Phase 2, each participant will undergo the same treatment (active or sham) of the Phase 1 for three months receiving stimulation once per week. The same psychometric and behavioral data of the phase 1 will be collected monthly. During Phase 3 participants will not receive any tDCS stimulation. Also in this phase, the same psychometric and behavioral data of the phase 1 will be collected monthly.

Eligibility criteria: Inclusion Criteria:

* diagnosis of Alcohol Use Disorder (at least 12 months);
* drug free/stable psychopharmacological therapy (one month), with the exception of guidelines treatments for alcoholic abstinence (treatment-as-usual);
* any assumption of substances for at least 48 hours.

Exclusion Criteria:

* presence of organic pathologies (capable of interfering with the safety of the procedure) in comorbidities;
* presence of intellectual disability;
* history of epileptic seizures (also in first degree relatives);
* score\> 12 on the Young Mania Rating Scale (Y-MRS).

Primary outcomes:
measure: Change in BDNF level
timeFrame: Baseline and after tDCS treatment: one week
measure: Change in pro-BDNF
timeFrame: Baseline and after tDCS treatment: one week
measure: Change in pro-BDNF/BDNF ratio.
timeFrame: Baseline and after tDCS treatment: one week
measure: Change in alcohol consumption as assessed by Alcohol Timeline Follow Back (TLFB-Alcohol)
timeFrame: Baseline, after tDCS treatment: one week, two weeks, 6 weeks, 3 months, 6 months
measure: Change in alcohol craving as assessed by the Visual Analog Scale for Craving (VAS 0-10 Craving)
timeFrame: Baseline, after tDCS treatment: one week, two weeks, 6 weeks, 3 months, 6 months
measure: Change in alcohol craving characteristics as assessed by the Brief Substance Craving Scale (BSCS)
timeFrame: Baseline, after tDCS treatment: one week, two weeks, 6 weeks, 3 months, 6 months
measure: Absence of alcohol intoxication evaluated by breathalyzer
timeFrame: Baseline, before the stimulation each day of treatment, each meeting of follow-up
measure: Evaluation of craving subtype assessed by the Craving Typology Questionnaire (CTQ)
timeFrame: Baseline
Secondary outcomes:
measure: Changes in Montgomery-Asberg Depression Scale (MADRS) Total Score
timeFrame: Baseline, after tDCS treatment: one week, two weeks, 6 weeks, 3 months, 6 months
measure: Change in substances consumption as assessed by Urine Drug Screen (UDS)
timeFrame: Baseline, after tDCS treatment: one week and randomly at follow-up meetings
measure: Changes in the Frontal Assessment Battery (FAB) Total Score
timeFrame: Baseline, after tDCS treatment: one week, two weeks, 6 weeks, 3 months, 6 months
measure: Changes in Hamilton Rating Scale for Anxiety (HAM-A) Total Score
timeFrame: Baseline, after tDCS treatment: one week, two weeks, 6 weeks, 3 months, 6 months
measure: Changes in Hamilton Rating Scale for Depression (HAM-D) 21 items Total Score
timeFrame: Baseline, after tDCS treatment: one week, two weeks, 6 weeks, 3 months, 6 months
measure: Changes in Barratt Impulsiveness Scale - 11 (BIS-11) Total Score
timeFrame: Baseline, after tDCS treatment: one week, two weeks, 6 weeks, 3 months, 6 months
measure: Changes in Toronto Alexithymia Scale (TAS-20) Total Score
timeFrame: Baseline, after tDCS treatment: one week, two weeks, 6 weeks, 3 months, 6 months
measure: Changes in Beck Depression Inventory-II scale (BDI-II) Total Score
timeFrame: Baseline, after tDCS treatment: one week, two weeks, 6 weeks, 3 months, 6 months
measure: Evaluation of South Oaks Gambling Screen (SOGS) Total Score
timeFrame: Baseline
measure: Changes in Leuven Affect and Pleasure Scale (LAPS) Total Score
timeFrame: Baseline, after tDCS treatment: one week, two weeks, 6 weeks, 3 months, 6 months
measure: Changes in Gambling Symptom Assessment Scale (G-SAS) Total Score
timeFrame: Baseline, after tDCS treatment: one week, two weeks, 6 weeks, 3 months, 6 months
measure: Changes in Young Mania Rating Scale (YMRS) Total Score
timeFrame: Baseline, after tDCS treatment: one week, two weeks, 6 weeks, 3 months, 6 months
measure: Changes in Brief Psychiatric Rating Scale Expanded (BPRS-E) Total Score
timeFrame: Baseline, after tDCS treatment: one week, two weeks, 6 weeks, 3 months, 6 months
measure: Evaluation of Questionnaire of sensations related to Transcranial Electrical Stimulation (TES) Total Score
timeFrame: After each tDCS treatment: Every day first week, once a week in the next three months.
measure: Evaluation of Stages of Change Readiness and Treatment Eagerness Scale (SOCRATES 8A) Total Score
timeFrame: Baseline
measure: Changes in Iowa Gambling Test (IGT)Total Score
timeFrame: Baseline, after tDCS treatment: one week, two weeks, 6 weeks, 3 months, 6 months
measure: Changes in Stroop Color and Word Test (SCWT) Total Score
timeFrame: Baseline, after tDCS treatment: one week, two weeks, 6 weeks, 3 months, 6 months
Other outcomes:
Locations:
Study officials:
affiliation: ITAB - Institute for Advanced Biomedical Technologies
name: Massimo di Giannantonio, MD
role: PRINCIPAL_INVESTIGATOR
References: