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

NCT ID: NCT04897295

Last Updated: 2021-10-26

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-12-01
• Study Completion Date: 2026-11-30

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.

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Active tDCS

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.

Group Type: ACTIVE_COMPARATOR

Active transcranial Direct Current Stimulation

Intervention Type: DEVICE

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

Sham tDCS

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.

Group Type: SHAM_COMPARATOR

Sham transcranial Direct Current Stimulation

Intervention Type: DEVICE

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

Interventions

Active transcranial Direct Current Stimulation

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

Intervention Type: DEVICE

Sham transcranial Direct Current Stimulation

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

Intervention Type: DEVICE

Other Intervention Names

Active tDCS; Sham tDCS

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).

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

ITAB - Institute for Advanced Biomedical Technologies

OTHER

Sponsor Role: lead

Responsible Party

Mauro Pettorruso

Junior Researcher

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Massimo di Giannantonio, MD

Role: PRINCIPAL_INVESTIGATOR

ITAB - Institute for Advanced Biomedical Technologies

Central Contacts

Mauro Pettorruso, MD, PhD

Role: CONTACT

Phone: +39 0871 355 6901

Email: mauro.pettorruso@unich.it

Other Identifiers

richdusea

Identifier Type: -

Identifier Source: org_study_id