Neurobiological Effects of Transcranial Direct Current Stimulation Treatment in Alcohol Use Disorder: a Sham-controlled Trial.
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 发起方
- 入组人数
- 30
- 主要终点
- Change in pro-BDNF
研究概览
简要总结
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
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Outcomes Assessor)
盲法说明
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.
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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).
结局指标
主要结局
Change in pro-BDNF
时间窗: 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 alcohol craving as assessed by the Visual Analog Scale for Craving (VAS 0-10 Craving)
时间窗: 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 BDNF level
时间窗: 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 alcohol consumption as assessed by Alcohol Timeline Follow Back (TLFB-Alcohol)
时间窗: 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 characteristics as assessed by the Brief Substance Craving Scale (BSCS)
时间窗: 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.
Evaluation of craving subtype assessed by the Craving Typology Questionnaire (CTQ)
时间窗: 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.
Change in pro-BDNF/BDNF ratio.
时间窗: 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.
Absence of alcohol intoxication evaluated by breathalyzer
时间窗: 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)
次要结局
- 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)
- 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 Brief Psychiatric Rating Scale Expanded (BPRS-E) Total Score(Baseline, after tDCS treatment: one week, two weeks, 6 weeks, 3 months, 6 months)
- Changes in Barratt Impulsiveness Scale - 11 (BIS-11) Total Score(Baseline, after tDCS treatment: one week, two weeks, 6 weeks, 3 months, 6 months)
- Evaluation of South Oaks Gambling Screen (SOGS) Total Score(Baseline)
- Changes in Young Mania Rating Scale (YMRS) Total Score(Baseline, after tDCS treatment: one week, two weeks, 6 weeks, 3 months, 6 months)
- Evaluation of Stages of Change Readiness and Treatment Eagerness Scale (SOCRATES 8A) Total Score(Baseline)
- Changes in Montgomery-Asberg Depression Scale (MADRS) 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 Toronto Alexithymia Scale (TAS-20) Total Score(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(Baseline, after tDCS treatment: one week, two weeks, 6 weeks, 3 months, 6 months)
- Changes in Gambling Symptom Assessment Scale (G-SAS) Total Score(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(After each tDCS treatment: Every day first week, once a week in the next three months.)
- Changes in Iowa Gambling Test (IGT)Total Score(Baseline, after tDCS treatment: one week, two weeks, 6 weeks, 3 months, 6 months)
- Changes in Stroop Color and Word Test (SCWT) Total Score(Baseline, after tDCS treatment: one week, two weeks, 6 weeks, 3 months, 6 months)
- Changes in Leuven Affect and Pleasure Scale (LAPS) Total Score(Baseline, after tDCS treatment: one week, two weeks, 6 weeks, 3 months, 6 months)
研究者
Mauro Pettorruso
Junior Researcher
ITAB - Institute for Advanced Biomedical Technologies