Alcohol Use Disorder (AUD)NCT04897295
Neurobiological Effects of Transcranial Direct Current Stimulation Treatment in Alcohol Use Disorder
A study testing Active transcranial Direct Current Stimulation in people with Alcohol Use Disorder (AUD) and Alcohol Abuse, run by ITAB - Institute for Advanced Biomedical Technologies.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Alcohol Use Disorder (AUD), Alcohol Abuse, Alcohol Dependence
- What is being tested?
- Active transcranial Direct Current Stimulation
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 30 participants
- Where
- No sites listed yet
- Study dates
- 1 Dec 2021to 30 Nov 2026
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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).
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
Official title: Neurobiological Effects of Transcranial Direct Current Stimulation Treatment in Alcohol Use Disorder: a Sham-controlled Trial.
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.
Read more
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
Read the 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.
- Conditions
- Alcohol Use Disorder (AUD), Alcohol Abuse, Alcohol Dependence, Alcohol-Related Disorders, Drug Abuse, Substance Use Disorders
- Being tested
- Active transcranial Direct Current Stimulation, Sham transcranial Direct Current Stimulation
- Keywords
- Alcohol Use Disorder, transcranial Direct Current Stimulation, Non-Invasive Brain Stimulation, Craving, Brain Derived Neurotrophic Factor, Pro-Brain Derived Neurotrophic Factor
- Medical subject headings
- Alcoholism, Alcohol-Related Disorders, Substance-Related Disorders, Mental Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Active transcranial Direct Current StimulationDevice
Also called Active tDCS
tDCS is a non-invasive brain stimulation technique. The investigators will use a BrainSTIM (EMS, Bologna, Italy)
Sham transcranial Direct Current StimulationDevice
Also called Sham tDCS
tDCS is a non-invasive brain stimulation technique. The investigators will use a BrainSTIM (EMS, Bologna, Italy)
| Study group | Role | What they receive |
|---|---|---|
| Active tDCS | Active comparator | The intervention will be the stimulation with transcranial Direct Current Stimulation (tDCS). Each patient will undergo a 20 minutes session with anode placed on the right Dorso-Lateral Prefrontal Cortex (RDLPFC) and the cathode on the left DLPFC (LDLPFC); the tDCS will administrate a 1 mA stimulation. During the intensive treatment phase participant will undergo one stimulation/day for 5 consecutive days. After this, participants will receive one stimulation per week for 3 months with the same parameters. Device: tDCS device (E.M.S. Electromedical Systems, Bologna, Italy) with a maximum output of 5 mA and administered by two 25-cm2 sponge electrodes of rectangular shape. Receives: Device: Active transcranial Direct Current Stimulation |
| Sham tDCS | Sham comparator | The intervention will be the stimulation with sham transcranial Direct Current Stimulation (sham tDCS). The device will be set by staff member not involved with data collection analysis to ensure the blinding of assessors. The device will be set to give a weak amperage for the first and the last 20 second of stimulation to ensure the blinding of participant giving them a similar sensation experienced by the active tDCS participants without stimulate brain tissues. Device: tDCS device (E.M.S. Electromedical Systems, Bologna, Italy) with a maximum output of 5 mA and administered by two 25-cm2 sponge electrodes of rectangular shape. Receives: Device: Sham transcranial Direct Current Stimulation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in BDNF level
BDNF levels will be evaluated by collecting a venous blood sample. BDNF is a member of the nerve growth factor (NGF) family of neurotrophic growth factors. Low levels of peripheral BDNF and NGF have been reported in mood disorders and other psychopathological conditions with normalization after antidepressant treatment or mood stabilization. The increase in serum levels of BDNF seems to reflect the concomitant activation of BDNF synthesis that accompanies the neuronal remodeling triggered by the suspension of alcohol intake and suggests that the synthesis of BDNF may have a role in the long-term maintenance of alcohol abstention. BDNF measurements will be calculated in pg/ml
Measured: Baseline and after tDCS treatment: one week
Change in pro-BDNF
Pro-BDNF is the precursor of BDNF and it acts as a repository of mature BDNF and acts itself by inducing neuronal thinning. Pro-BDNF levels will be evaluated by collecting a venous blood sample. Pro-BDNF measurements will be calculated in ng/ml.
Measured: Baseline and after tDCS treatment: one week
Change in pro-BDNF/BDNF ratio.
Pro-BDNF/BDNF ratio, seems to be a more specific measurement of the early changes in the metabolism of BDNF. Its level seems to correlate to more or less a neurotrophic and neuroprotective action of BDNF.
Measured: Baseline and after tDCS treatment: one week
Change in alcohol consumption as assessed by Alcohol Timeline Follow Back (TLFB-Alcohol)
The TLFB is a calendar-based interview method in which the individual retrospectively identifies the days when alcohol was assumed, and the number of standard drinks consumed on those days. // Alcohol consumption will be assessed using the TimeLine Follow Back (TLFB). TLFB is an interview-based assessment. Using a calendar, participants are guided through the process of recalling and reporting daily alcohol consumption. TLFB provides measures of alcohol consumption per week, alcohol consuming days per week, heavy alcohol consuming days per week.
Measured: Baseline, after tDCS treatment: one week, two weeks, 6 weeks, 3 months, 6 months
Change in alcohol craving as assessed by the Visual Analog Scale for Craving (VAS 0-10 Craving)
Alcohol craving intensity will be assessed using a visual analog scale (VAS). Participants sign subjective feelings of craving on a 10 cm line marked from zero (null) to 10 (the most intense).
Measured: Baseline, after tDCS treatment: one week, two weeks, 6 weeks, 3 months, 6 months
Change in alcohol craving characteristics as assessed by the Brief Substance Craving Scale (BSCS)
Alcohol craving will be assessed using the Brief Substance Craving Scale (BSCS). The BSCS is a 16 item, self-report instrument assesses craving for substances of abuse over a 24 hour period.
Measured: Baseline, after tDCS treatment: one week, two weeks, 6 weeks, 3 months, 6 months
Absence of alcohol intoxication evaluated by breathalyzer
Alcohol consumption will be evaluated by breathalyzer. Breathalyzer measures breath alcohol concentration (BrAC) levels; the BrAC-data was interpreted as blood alcohol content (BAC). Semi-quantitative analyses are performed. The breathalyzer can differentiate five levels: negative (0 - 0.07 gr / L), low (0.07 - 0.3 gr / L), warn (0.31 - 0.5 gr / L), fall (0.51 - 0.8 gr / L), fall + (> 0.8 gr / L)
Measured: Baseline, before the stimulation each day of treatment, each meeting of follow-up
Evaluation of craving subtype assessed by the Craving Typology Questionnaire (CTQ)
Alcohol craving subtype will be assessed using the Craving Typology Questionnaire (CTQ). It is a self-report questionnaire measuring three supposedly independent typologies of alcohol craving: relief, obsessive and reward craving.
Measured: Baseline
Secondary outcomes (17)
Changes in Montgomery-Asberg Depression Scale (MADRS) Total Score
The MADRS is a 10-item scale that evaluates the core symptoms and cognitive features of clinical depression. Each MADRS item is rated on a 0 to 6 scale. The MADRS Total score ranges from 0 (min) to 60 (max). Higher MADRS scores indicate higher levels of depressive symptoms.
Measured: Baseline, after tDCS treatment: one week, two weeks, 6 weeks, 3 months, 6 months
Change in substances consumption as assessed by Urine Drug Screen (UDS)
Substances consumption will be evaluated by Urine Drug Screen (UDS). Urine Drug Screen is a test to evaluate the presence of substances of abuse in urine samples. Quantitative analyses are not performed. Test may be positive or negative for the presence of substances of abuse.
Measured: Baseline, after tDCS treatment: one week and randomly at follow-up meetings
Changes in the Frontal Assessment Battery (FAB) Total Score
Frontal Assessment Battery (FAB) is a short neuropsychological tool aimed at assessing executive functions. The FAB consists of six subtests, each exploring functions related to the frontal lobes: conceptualization (by means of a similarities task), mental flexibility (by means of a phonological fluency task), motor programming (by means of Luria's motor series), sensitivity to interference (by means of a conflicting instruction task), inhibitory control (by means of a go-no-go task), and environmental autonomy (by means of evaluation of prehension behavior). Each subtest score may range from 0 (min) to 3 (max); total score is from 0 (min) to 18 (max). Higher scores indicate better performance.
Measured: Baseline, after tDCS treatment: one week, two weeks, 6 weeks, 3 months, 6 months
Changes in Hamilton Rating Scale for Anxiety (HAM-A) Total Score
The HAM-A is a 14-item scale that assesses anxiety symptoms of anxiety such as "anxious mood", "tension" or "fears". Each item is scored on a 5-point scale, ranging from 0 (not present) to 4 (severe). Sum the scores from all 14 parameters gives the HAM-A Total Score which may range from 0 (min) to 56 (max).
Measured: Baseline, after tDCS treatment: one week, two weeks, 6 weeks, 3 months, 6 months
Changes in Hamilton Rating Scale for Depression (HAM-D) 21 items Total Score
The HAM-D is a 21-item scale that measures the severity of depressive symptoms and additional clinical information (diurnal variation, depersonalization/derealization, paranoid symptoms, and obsessive-compulsive symptoms). The severity of depression is divided into 4 categories as follows: 0-7 is considered as normal patients, 8-16 suggesting mild depression, 17-23 suggesting moderate depression and scores over 24 indicating severe depression. The total HDRS score ranged from 0 to a maximum of 52 points.
Measured: Baseline, after tDCS treatment: one week, two weeks, 6 weeks, 3 months, 6 months
Changes in Barratt Impulsiveness Scale - 11 (BIS-11) Total Score
The Barratt Impulsiveness Scale 11th version (BIS-11) is a 30-item scale that assesses impulsivity. The BIS-11 was developed to specifically measure impulsiveness, in contrast to other "action-oriented" traits such as sensation-seeking, extraversion, and risk taking. The total BIS-11 score ranged from 30 to a maximum of 120 points. Higher scale scores indicate higher levels of impulsiveness.
Measured: Baseline, after tDCS treatment: one week, two weeks, 6 weeks, 3 months, 6 months
Changes in Toronto Alexithymia Scale (TAS-20) Total Score
The TAS-20 is a self-report scale that assesses alexithymia. It is comprised of 20 items assessing three dimensions of alexithymia, i.e., Difficulty Identifying Feelings (DIF), Difficulty Describing Feelings (DDF), and Externally Oriented Thinking (EOT). Each of the twenty items is rated on a 5-point Likert scale. Increasing scores indicate higher degrees of alexithymia. The TAS-20 uses cutoff scoring: equal to or less than 51 = non-alexithymia, equal to or greater than 61 = alexithymia. Scores of 52 to 60 = possible alexithymia.
Measured: Baseline, after tDCS treatment: one week, two weeks, 6 weeks, 3 months, 6 months
Changes in Beck Depression Inventory-II scale (BDI-II) Total Score
The BDI-II is a 21-item self-report measure of depressive symptoms. Each of the 21 items corresponding to a symptom of depression is summed to give a single score for the Beck Depression Inventory-II (BDI-II). There is a four-point scale for each item ranging from 0 to 3. On two items (16 and 18) there are seven options to indicate either an increase or decrease of appetite and sleep. Cut-off score guidelines for the BDI-II are given with the recommendation that thresholds be adjusted based on the characteristics of the sample, and the purpose for use of the BDI-II. Total score of 0-13 is considered minimal range, 14-19 is mild, 20-28 is moderate, and 29-63 is severe.
Measured: Baseline, after tDCS treatment: one week, two weeks, 6 weeks, 3 months, 6 months
Evaluation of South Oaks Gambling Screen (SOGS) Total Score
The SOGS is a 20-item instrument to screen for probable pathological gambling. A cut score of 5 or more is typically used to indicate that the individual is a probable pathological gambler.
Measured: Baseline
Changes in Leuven Affect and Pleasure Scale (LAPS) Total Score
The LAPS is a 16-item questionnaire to assess negative affect, positive affect, and hedonic tone. The 16-item scale comprises 3 subscales (negative affect, positive affect, hedonic tone) and 4 independent items (cognitive functioning, overall functioning, my life is meaningful, I feel happy). Patients rate their positive and negative moods, and hedonic tone from 0 to 10, where 0 is not at all, 1-3 are scores for a little bit, 4-6 are scores for moderately, 7-9 are scores for quite a bit and 10 represents very much.
Measured: Baseline, after tDCS treatment: one week, two weeks, 6 weeks, 3 months, 6 months
Changes in Gambling Symptom Assessment Scale (G-SAS) Total Score
The G-SAS is a 12-item self-rated scale designed to assess gambling symptom severity and change during treatment. Each 12-item scale has a score ranging from 0 - 4 (adjective anchors for 0 and 4 vary for each item). All items ask for an average symptom based on the past 7 days. Total score ranges from 0 - 48: extreme = 41 - 48, severe = 31 - 40, moderate = 21 - 30, mild = 8 - 20.
Measured: Baseline, after tDCS treatment: one week, two weeks, 6 weeks, 3 months, 6 months
Changes in Young Mania Rating Scale (YMRS) Total Score
The Y-MRS is a 11-item scale to assess manic symptoms based on the patient's subjective report of his or her clinical condition over the previous 48hours. Additional information is based upon clinical observations made during the clinical interview. YMRS cut-off values were minimal (13), mild (20), moderate (26), and severe (38) manic symptoms.
Measured: Baseline, after tDCS treatment: one week, two weeks, 6 weeks, 3 months, 6 months
Changes in Brief Psychiatric Rating Scale Expanded (BPRS-E) Total Score
The BPRS-E is a 24-item scale for assessing type, severity and change over time of 24 psychiatric symptoms. The presence and severity of psychiatric symptoms were rated on a Likert scale ranging from 1 (not present) to 7 (extremely severe). Thus, possible scores vary from 24 to 168 with lower scores indicating less severe psychopathology.
Measured: Baseline, after tDCS treatment: one week, two weeks, 6 weeks, 3 months, 6 months
Evaluation of Questionnaire of sensations related to Transcranial Electrical Stimulation (TES) Total Score
The TES is a short tool aimed at assessing any possible discomfort during the electrical stimulation (e.g., itching, pain or burning), the duration and the degree of intensity discomfort.
Measured: After each tDCS treatment: Every day first week, once a week in the next three months.
Evaluation of Stages of Change Readiness and Treatment Eagerness Scale (SOCRATES 8A) Total Score
- The SOCRATES 8A is a 19-items scale that measures participants general level of motivation. SOCRATES 8A assess strengths and needs in the areas of treatment readiness, motivation of problem drinkers and drug users for change and to enter treatment. It provides scores on three subscales- Recognition, Ambivalence and Taking steps.
Measured: Baseline
Changes in Iowa Gambling Test (IGT)Total Score
The IGT is a computer-administered neuro-psychological test to evaluate decision-making abilities. It consists of 100 card selections from four decks of cards divided into five distinct blocks of 20 trials each to examine participant's learning curve. A total score for the IGT is calculated by subtracting the total number of selections from the bad decks from the total number of selections from the good deck. A positive total score indicates advantageous decision-making, whereas a negative total score indicates disadvantageous decision-making.
Measured: Baseline, after tDCS treatment: one week, two weeks, 6 weeks, 3 months, 6 months
Changes in Stroop Color and Word Test (SCWT) Total Score
The SCWT evaluates attention, information processing speed, selective attention, cognitive flexibility and the ability to inhibit cognitive interference of simultaneous stimulus. The SCWT evaluates the reaction times to non-ambiguous stimuli and to ambiguous stimuli.
Measured: Baseline, after tDCS treatment: one week, two weeks, 6 weeks, 3 months, 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 May 2021
- Study start1 Dec 2021 (estimated)
- Primary completion31 Jul 2026 (estimated)
- Study completion30 Nov 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Alcohol Use Disorder (AUD)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- double blind, randomized, sham-controlled with a 1:1 allocation into 2 parallel arms
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- ITAB - Institute for Advanced Biomedical Technologies
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Mauro Pettorruso, ITAB - Institute for Advanced Biomedical Technologies
- Investigators
- Massimo di Giannantonio, MD, Principal investigator, ITAB - Institute for Advanced Biomedical Technologies
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04897295
- Sponsor's protocol ID
- richdusea
- Status last verified
- Oct 2021
- First submitted
- 27 Feb 2021
- Last updated
- 26 Oct 2021
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 26 Oct 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Neurobiological Effects of Transcranial Direct Current Stimulation Treatment in Alcohol Use Disorder: a Sham-controlled Trial.
- ClinicalTrials.gov ID
- NCT04897295
- Acronym / sponsor ID
- richdusea
- Conditions
- Alcohol Use Disorder (AUD), Alcohol Abuse, Alcohol Dependence, Alcohol-Related Disorders, Drug Abuse, Substance Use Disorders
- Keywords
- Alcohol Use Disorder, transcranial Direct Current Stimulation, Non-Invasive Brain Stimulation, Craving, Brain Derived Neurotrophic Factor, Pro-Brain Derived Neurotrophic Factor
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- ITAB - Institute for Advanced Biomedical TechnologiesUniversity, hospital or other
- Study start
- 1 Dec 2021 (estimated)
- Primary completion
- 31 Jul 2026 (estimated)
- Study completion
- 30 Nov 2026 (estimated)
- First posted
- 21 May 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
- Model description
- double blind, randomized, sham-controlled with a 1:1 allocation into 2 parallel arms
| Arm | Type | Receives |
|---|---|---|
| Active tDCS | Active comparator | Device: Active transcranial Direct Current StimulationThe intervention will be the stimulation with transcranial Direct Current Stimulation (tDCS). Each patient will undergo a 20 minutes session with anode placed on the right Dorso-Lateral Prefrontal Cortex (RDLPFC) and the cathode on the left DLPFC (LDLPFC); the tDCS will administrate a 1 mA stimulation. During the intensive treatment phase participant will undergo one stimulation/day for 5 consecutive days. After this, participants will receive one stimulation per week for 3 months with the same parameters. Device: tDCS device (E.M.S. Electromedical Systems, Bologna, Italy) with a maximum output of 5 mA and administered by two 25-cm2 sponge electrodes of rectangular shape. |
| Sham tDCS | Sham comparator | Device: Sham transcranial Direct Current StimulationThe intervention will be the stimulation with sham transcranial Direct Current Stimulation (sham tDCS). The device will be set by staff member not involved with data collection analysis to ensure the blinding of assessors. The device will be set to give a weak amperage for the first and the last 20 second of stimulation to ensure the blinding of participant giving them a similar sensation experienced by the active tDCS participants without stimulate brain tissues. Device: tDCS device (E.M.S. Electromedical Systems, Bologna, Italy) with a maximum output of 5 mA and administered by two 25-cm2 sponge electrodes of rectangular shape. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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.
Key exclusion criteria (4 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Active transcranial Direct Current StimulationAlso: Active tDCStDCS is a non-invasive brain stimulation technique. The investigators will use a BrainSTIM (EMS, Bologna, Italy) | Device | Active tDCS |
| Sham transcranial Direct Current StimulationAlso: Sham tDCStDCS is a non-invasive brain stimulation technique. The investigators will use a BrainSTIM (EMS, Bologna, Italy) | Device | Sham tDCS |
Primary outcome
Change in BDNF level
Time frame: Baseline and after tDCS treatment: one week
BDNF levels will be evaluated by collecting a venous blood sample. BDNF is a member of the nerve growth factor (NGF) family of neurotrophic growth factors. Low levels of peripheral BDNF and NGF have been reported in mood disorders and other psychopathological conditions with normalization after antidepressant treatment or mood stabilization. The increase in serum levels of BDNF seems to reflect the concomitant activation of BDNF synthesis that accompanies the neuronal remodeling triggered by the suspension of alcohol intake and suggests that the synthesis of BDNF may have a role in the long-term maintenance of alcohol abstention. BDNF measurements will be calculated in pg/ml
Change in pro-BDNF
Time frame: Baseline and after tDCS treatment: one week
Pro-BDNF is the precursor of BDNF and it acts as a repository of mature BDNF and acts itself by inducing neuronal thinning. Pro-BDNF levels will be evaluated by collecting a venous blood sample. Pro-BDNF measurements will be calculated in ng/ml.
Change in pro-BDNF/BDNF ratio.
Time frame: Baseline and after tDCS treatment: one week
Pro-BDNF/BDNF ratio, seems to be a more specific measurement of the early changes in the metabolism of BDNF. Its level seems to correlate to more or less a neurotrophic and neuroprotective action of BDNF.
Change in alcohol consumption as assessed by Alcohol Timeline Follow Back (TLFB-Alcohol)
Time frame: Baseline, after tDCS treatment: one week, two weeks, 6 weeks, 3 months, 6 months
The TLFB is a calendar-based interview method in which the individual retrospectively identifies the days when alcohol was assumed, and the number of standard drinks consumed on those days. // Alcohol consumption will be assessed using the TimeLine Follow Back (TLFB). TLFB is an interview-based assessment. Using a calendar, participants are guided through the process of recalling and reporting daily alcohol consumption. TLFB provides measures of alcohol consumption per week, alcohol consuming days per week, heavy alcohol consuming days per week.
Change in alcohol craving as assessed by the Visual Analog Scale for Craving (VAS 0-10 Craving)
Time frame: Baseline, after tDCS treatment: one week, two weeks, 6 weeks, 3 months, 6 months
Alcohol craving intensity will be assessed using a visual analog scale (VAS). Participants sign subjective feelings of craving on a 10 cm line marked from zero (null) to 10 (the most intense).
Change in alcohol craving characteristics as assessed by the Brief Substance Craving Scale (BSCS)
Time frame: Baseline, after tDCS treatment: one week, two weeks, 6 weeks, 3 months, 6 months
Alcohol craving will be assessed using the Brief Substance Craving Scale (BSCS). The BSCS is a 16 item, self-report instrument assesses craving for substances of abuse over a 24 hour period.
Absence of alcohol intoxication evaluated by breathalyzer
Time frame: Baseline, before the stimulation each day of treatment, each meeting of follow-up
Alcohol consumption will be evaluated by breathalyzer. Breathalyzer measures breath alcohol concentration (BrAC) levels; the BrAC-data was interpreted as blood alcohol content (BAC). Semi-quantitative analyses are performed. The breathalyzer can differentiate five levels: negative (0 - 0.07 gr / L), low (0.07 - 0.3 gr / L), warn (0.31 - 0.5 gr / L), fall (0.51 - 0.8 gr / L), fall + (> 0.8 gr / L)
Evaluation of craving subtype assessed by the Craving Typology Questionnaire (CTQ)
Time frame: Baseline
Alcohol craving subtype will be assessed using the Craving Typology Questionnaire (CTQ). It is a self-report questionnaire measuring three supposedly independent typologies of alcohol craving: relief, obsessive and reward craving.
17 secondary outcomes
Changes in Montgomery-Asberg Depression Scale (MADRS) Total Score
Time frame: Baseline, after tDCS treatment: one week, two weeks, 6 weeks, 3 months, 6 months
Change in substances consumption as assessed by Urine Drug Screen (UDS)
Time frame: Baseline, after tDCS treatment: one week and randomly at follow-up meetings
Changes in the Frontal Assessment Battery (FAB) Total Score
Time frame: Baseline, after tDCS treatment: one week, two weeks, 6 weeks, 3 months, 6 months
Changes in Hamilton Rating Scale for Anxiety (HAM-A) Total Score
Time frame: Baseline, after tDCS treatment: one week, two weeks, 6 weeks, 3 months, 6 months
Changes in Hamilton Rating Scale for Depression (HAM-D) 21 items Total Score
Time frame: Baseline, after tDCS treatment: one week, two weeks, 6 weeks, 3 months, 6 months
Changes in Barratt Impulsiveness Scale - 11 (BIS-11) Total Score
Time frame: Baseline, after tDCS treatment: one week, two weeks, 6 weeks, 3 months, 6 months
Changes in Toronto Alexithymia Scale (TAS-20) Total Score
Time frame: Baseline, after tDCS treatment: one week, two weeks, 6 weeks, 3 months, 6 months
Changes in Beck Depression Inventory-II scale (BDI-II) Total Score
Time frame: Baseline, after tDCS treatment: one week, two weeks, 6 weeks, 3 months, 6 months
Evaluation of South Oaks Gambling Screen (SOGS) Total Score
Time frame: Baseline
Changes in Leuven Affect and Pleasure Scale (LAPS) Total Score
Time frame: Baseline, after tDCS treatment: one week, two weeks, 6 weeks, 3 months, 6 months
Changes in Gambling Symptom Assessment Scale (G-SAS) Total Score
Time frame: Baseline, after tDCS treatment: one week, two weeks, 6 weeks, 3 months, 6 months
Changes in Young Mania Rating Scale (YMRS) Total Score
Time frame: Baseline, after tDCS treatment: one week, two weeks, 6 weeks, 3 months, 6 months
Changes in Brief Psychiatric Rating Scale Expanded (BPRS-E) Total Score
Time frame: Baseline, after tDCS treatment: one week, two weeks, 6 weeks, 3 months, 6 months
Evaluation of Questionnaire of sensations related to Transcranial Electrical Stimulation (TES) Total Score
Time frame: After each tDCS treatment: Every day first week, once a week in the next three months.
Evaluation of Stages of Change Readiness and Treatment Eagerness Scale (SOCRATES 8A) Total Score
Time frame: Baseline
Changes in Iowa Gambling Test (IGT)Total Score
Time frame: Baseline, after tDCS treatment: one week, two weeks, 6 weeks, 3 months, 6 months
Changes in Stroop Color and Word Test (SCWT) Total Score
Time frame: Baseline, after tDCS treatment: one week, two weeks, 6 weeks, 3 months, 6 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Oct 2021.
- Individual participant dataSharing planned: No
Related trials for Alcohol Use Disorder (AUD)
Not yet recruiting
A MRT to Optimize a JITAI for Alcohol Craving and Suicide Ideation
Alcohol Use Disorder (AUD), Suicide Ideation
Not yet recruiting
Examining the Relationship Between Ongoing Alcohol Use, Suicidal Thoughts and Behaviors and Related Constructs, and Behavioral Economic Decision-Making.
Alcohol Use Disorder (AUD), Suicidal Ideation
Not yet recruitingObservational study
Disease Intervention Specialist (DIS) for SUD
Substance Use Disorder (SUD), Opioid Use Disorder
Not yet recruiting
Deaf CBT-TS to Reduce Suicide Risk
Depression - Major Depressive Disorder, Anxiety
Not yet recruiting
eTSF for Latinx Young Adults With Alcohol Use Disorder
Alcohol Use Disorder (AUD)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Massimo di Giannantonio, MD principal investigator
ITAB - Institute for Advanced Biomedical Technologies
Questions about this trial
What is this clinical trial studying?
A study testing Active transcranial Direct Current Stimulation in people with Alcohol Use Disorder (AUD) and Alcohol Abuse, run by ITAB - Institute for Advanced Biomedical Technologies.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 26 Oct 2021. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Mauro Pettorruso, MD, PhD (+39 0871 355 6901, mauro.pettorruso@unich.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in BDNF level (time frame: Baseline and after tDCS treatment: one week). The study lists 8 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Oct 2021.