Neurobiological Effects of Transcranial Direct Current Stimulation Treatment in Alcohol Use Disorder

NCT04897295 | Not Yet Recruiting

• 1 other identifier: richdusea
• Study Type: interventional
• Target: 30
• Locations: 0 countries
• Sites: N/A

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

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

Outcome Measures

Primary Outcomes (8)

• 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

  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.

  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.

  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.

  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).

  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.

  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)

  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.

  Baseline

Secondary Outcomes (17)

• Changes in Montgomery-Asberg Depression Scale (MADRS) Total Score

  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)

  Baseline, after tDCS treatment: one week and randomly at follow-up meetings

• Changes in the Frontal Assessment Battery (FAB) Total Score

  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

  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

  Baseline, after tDCS treatment: one week, two weeks, 6 weeks, 3 months, 6 months

Study Arms (2)

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.

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.

Device: Sham transcranial Direct Current Stimulation

Interventions

Active transcranial Direct Current Stimulation DEVICE

tDCS is a non-invasive brain stimulation technique. The investigators will use a BrainSTIM (EMS, Bologna, Italy)

Also known as: Active tDCS

Active tDCS

Sham transcranial Direct Current Stimulation DEVICE

tDCS is a non-invasive brain stimulation technique. The investigators will use a BrainSTIM (EMS, Bologna, Italy)

Also known as: Sham tDCS

Sham tDCS

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• ITAB - Institute for Advanced Biomedical Technologies: lead

MeSH Terms

Conditions

Alcoholism; Alcohol-Related Disorders; Substance-Related Disorders; Mental Disorders

Condition Hierarchy (Ancestors)

Chemically-Induced Disorders

Study Officials

• Massimo di Giannantonio, MD

  ITAB - Institute for Advanced Biomedical Technologies

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Mauro Pettorruso, MD, PhD

CONTACT

+39 0871 355 6901; mauro.pettorruso@unich.it

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Masking Details: To ensure the allocation concealment of participants, the sham group will receive a stimulation with a weak amperage for only the first and the last 20 seconds of the session, giving them a similar sensation experienced by the active tDCS. The assessors will never stimulate participants to ensure the blind condition.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Junior Researcher

Model Details: double blind, randomized, sham-controlled with a 1:1 allocation into 2 parallel arms

Study Record Dates

• First Submitted: February 27, 2021
• First Posted: May 21, 2021
• Study Start: December 1, 2021
• Primary Completion (Estimated): July 31, 2026
• Study Completion (Estimated): November 30, 2026
• Last Updated: October 26, 2021

Record last verified: 2021-10

Data Sharing

• IPD Sharing: Will not share