Bilateral Prefrontal Modulation in Alcoholism

Executive Dysfunction Clinical Trial

— tDCS_ALCOHOL  

Official title:

Prefrontal Modulation by Repetitive Bilateral Transcranial Direct Current Stimulation (tDCS) in Alcoholic Inpatients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02091284
• Other study ID #: tDCS ALCOHOL CEP_UFES 384281
• Secondary ID: CNPq_ 475232/201
• Status: Completed
• Phase: N/A
• Start date: November 2013
• Est. completion date: July 3, 2018

Study information

• Verified date: June 2019
• Source: Federal University of Espirito Santo
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

In this study, eligible alcoholic inpatients recruited from a specialized clinic for addiction treatment, filling inclusion criteria and not showing any exclusion criteria, were randomized to receive the repetitive (10 sessions, every other day) bilateral dorsolateral Prefrontal Cortex (dlPFC: cathodal left / anodal right) tDCS (2 milliamperes, 5 x 7 cm2, for 20 min) or placebo (sham-tDCS). Craving to the use of alcohol was examined before (baseline), during and after the end of the tDCS treatment.

Based in our previous data, our hypothesis was that repetitive bilateral tDCS over dlPFC would favorably change craving in alcoholism and this would be a long-lasting effect.

Description:

Before (baseline) and after tDCS or sham-tDCS treatment, subjects were clinically examined regarding craving (obsessive compulsive drinking scale) and they were followed-up for relapses at least 3 months after treatment.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 49
• Est. completion date: July 3, 2018
• Est. primary completion date: July 3, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

Inclusion Criteria:

• patients between the age of 18 and 60 years;

• met criteria for alcohol dependence according to the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV), as determined by clinical evaluation;

• in stable clinical condition with no need for inpatient care;

• able to read, write, and speak Portuguese; and

• no severe withdrawal signs or symptoms at baseline.

Exclusion Criteria:

• a condition of intoxication or withdrawal due to a substance other alcohol;

• unstable mental or medical disorder or substance abuse or addiction other than alcohol dependence, except nicotine and/or caffeine;

• a diagnosis of epilepsy, convulsions, or delirium tremens during abstinence from alcohol;

• a previous history of drug hypersensitivity or adverse reactions to diazepam or other benzodiazepines and haloperidol;

• any contraindication for electrical brain stimulation procedures such as electronic implants or metal implants;

• suspected pregnancy for female participants;

• any contraindication for magnetic resonance procedures such as electronic implants, metal implants, claustrophobia, or permanent make-up or tattoo received within the previous 3 months;

• the presence of vascular, traumatic, inflammatory, or tumor injuries detectable by CT examination.

Related Conditions & MeSH terms

• Alcoholism
• Drug Addiction
• Executive Dysfunction
• Substance-Related Disorders

Intervention

Device:
• transcranial Direct Current Stimulation
Direct currents were transferred via a pair of carbonated-silicone electrodes (35 cm2) with a thick layer of high conductive gel for EEG underneath them. The electric current will be delivered by an electric stimulator. To stimulate the left DLPFC, the cathode electrode was placed over F3 according to the 10-20 international system while the anode was placed over the contralateral F4 region. The currents flowed continuously for 20 minutes with an intensity of 2 milliamperes.

Locations

Country	Name	City	State
Brazil	Federal University of Espírito Santo	Vitória	ES - Espírito Santo

Sponsors (4)

Lead Sponsor	Collaborator
Federal University of Espirito Santo	Conselho Nacional de Desenvolvimento Científico e Tecnológico, Harvard Medical School, University of Göttingen

Country where clinical trial is conducted

Brazil, 

References & Publications (4)

da Silva MC, Conti CL, Klauss J, Alves LG, do Nascimento Cavalcante HM, Fregni F, Nitsche MA, Nakamura-Palacios EM. Behavioral effects of transcranial direct current stimulation (tDCS) induced dorsolateral prefrontal cortex plasticity in alcohol dependence. J Physiol Paris. 2013 Dec;107(6):493-502. doi: 10.1016/j.jphysparis.2013.07.003. Epub 2013 Jul 25. — View Citation

Klauss J, Anders QS, Felippe LV, Nitsche MA, Nakamura-Palacios EM. Multiple Sessions of Transcranial Direct Current Stimulation (tDCS) Reduced Craving and Relapses for Alcohol Use: A Randomized Placebo-Controlled Trial in Alcohol Use Disorder. Front Pharm — View Citation

Klauss J, Penido Pinheiro LC, Silva Merlo BL, de Almeida Correia Santos G, Fregni F, Nitsche MA, Miyuki Nakamura-Palacios E. A randomized controlled trial of targeted prefrontal cortex modulation with tDCS in patients with alcohol dependence. Int J Neuropsychopharmacol. 2014 Nov;17(11):1793-803. doi: 10.1017/S1461145714000984. Epub 2014 Jul 10. — View Citation

Nakamura-Palacios EM, Souza RS, Zago-Gomes MP, de Melo AM, Braga FS, Kubo TT, Gasparetto EL. Gray matter volume in left rostral middle frontal and left cerebellar cortices predicts frontal executive performance in alcoholic subjects. Alcohol Clin Exp Res. 2014 Apr;38(4):1126-33. doi: 10.1111/acer.12308. Epub 2013 Nov 20. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Changes in Frontal Assessment Battery (FAB) Scores	The FAB was used to explore six different domains of executive function. Each of these items is scored from 0 (zero) to a maximum of 3. Thus, the maximum score, meaning better scores, of FAB is 18. A single well trained examiner administered this assessment.	Before tDCS treatment (initial) and after the end of the tDCS treatment (final)
Other	Changes in Mini-Mental Status Examination (MMSE)	An adapted version of the MMSE in Portuguese was used. This version included an 11-item examination that examined five areas of cognitive function: orientation, registration, attention and calculation, recall, and language. The maximum score, meaning better scores, that could be achieved was 30, while a mean score between 23 and 26 or between 26 and 29 would be expected according to the age and educational level of the alcoholics.	Before tDCS treatment (initial) and after the end of the tDCS treatment (final)
Other	Changes in Hamilton Depression Rating Scale (HAM-D)	A structured multiple-choice questionnaire was used to assess the severity of depression symptoms. This instrument assesses the severity of symptoms observed in depression, such as low mood, insomnia, agitation, anxiety and weight loss (Hamilton, 1960). Each question has between 3 and 5 possible answers that increase in severity. In the original scale, the first 17 questions contribute to the total score, while questions 18 to 21 provide additional information about depression (e.g., diurnal variation, paranoid symptoms), but are not included in the total score of the scale. Scores of 0-7 are considered as being normal, 8-16 suggest mild depression, 17-23 moderate depression and scores over 24 are indicative of severe depression; the maximum score is 52.	Before tDCS treatment (initial) and after the end of the tDCS treatment (final)
Other	Changes in Hamilton Anxiety Rating Scale (HAM-A)	A structured multiple-choice questionnaire designed to assess the severity of anxiety symptoms was employed. The scale consists of 14 items, each defined by a series of symptoms, and measures both psychic anxiety (e.g., mental agitation and psychological distress) and somatic anxiety (e.g., physical complaints related to anxiety). The higher the scores, higher the severity. Each item is scored on a scale of 0 (not present) to 4 (severe), with a total score range of 0-56, where below 17 indicates mild severity, 18-24 mild to moderate severity and 25-30 moderate to severe.	Before tDCS treatment (initial) and after the end of the tDCS treatment (final)
Other	Changes in Event-Related Potentials (ERPs)	Electrophysiological recording was obtained through a 32-channel system placed on the scalp according to the International 10/20 EEG system.; A cue-reactivity paradigm was adapted following standard cue-reactivity paradigms well established for pictures and videos. During picture presentation the subjects were asked to press a button whenever the drug-related pictures were presented, and to withhold the response when the neutral pictures were presented (50% of the time). The percent change of ventral medial Prefrontal Cortex current density was analyzed.	Before tDCS treatment (initial) and after the end of the tDCS treatment (final)
Other	Changes in Quality of Life of the World Health Organization (WHOQOL-BREF)	An abbreviated instrument of cross-culturally valid assessment of quality of life of the World Health Organization (WHOQOL-BREF) with 26 questions translated to Portuguese was applied at the beginning and at the end of the five-week treatment. This instrument yields four domains (physical health, psychological, social relationships and environment) and two individually scored items regarding overall perception of quality of life (Q1, i.e., first question) and health (Q2, i.e., second question). The four domain scores are scaled in a way that higher scores stand for higher quality of life. These scores were transformed to be comparable with the scores used in the WHOQOL-100.	Before tDCS treatment (initial) and after the end of the tDCS treatment (final)
Primary	Craving	Five items from the original obsessive compulsive drinking scale, which are believed to reliably assess craving in a narrow sense were used. Questions of this brief scale allow quantification of thoughts and feelings (obsessions), and behavioral intentions, and are answered on a scale ranging from 0 to 4, resulting in a total score between 0 and 20. Higher scores reflect more severe craving. These items were applied at the beginning, during and at the end of the treatment with sham-tDCS or tDCS.	Five applications: first week before tDCS treatment (baseline), second, third and fourth weeks, during the treatment, and in the fifth week, after the end of the tDCS treatment.