Bilateral Prefrontal Modulation in Alcoholism

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

Status

Completed

Phases

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02091284

Acronym

tDCS_ALCOHOL

Enrollment

Registered

2014-03-19

Start date

2013-11-30

Completion date

2018-07-03

Last updated

2019-08-08

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Drug Addiction, Executive Dysfunction

Keywords

alcoholism, tDCS, dlPFC, craving, cognition

Brief 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.

Detailed 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.

Interventions

DEVICEtranscranial 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.

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

TRIPLE (Subject, Caregiver, Outcomes Assessor)

Intervention model description

Sham-controlled double-blind randomized trial

Eligibility

Sex/Gender

ALL

Age

18 Years to 60 Years

Healthy volunteers

Yes

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.

Design outcomes

Primary

Measure	Time frame	Description
Craving	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.	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.

Other

Measure	Time frame	Description
Changes in Frontal Assessment Battery (FAB) Scores	Before tDCS treatment (initial) and after the end of the tDCS treatment (final)	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.
Changes in Mini-Mental Status Examination (MMSE)	Before tDCS treatment (initial) and after the end of the tDCS treatment (final)	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.
Changes in Hamilton Depression Rating Scale (HAM-D)	Before tDCS treatment (initial) and after the end of the tDCS treatment (final)	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.
Changes in Hamilton Anxiety Rating Scale (HAM-A)	Before tDCS treatment (initial) and after the end of the tDCS treatment (final)	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.
Changes in Event-Related Potentials (ERPs)	Before tDCS treatment (initial) and after the end of the tDCS treatment (final)	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.
Changes in Quality of Life of the World Health Organization (WHOQOL-BREF)	Before tDCS treatment (initial) and after the end of the tDCS treatment (final)	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.

Countries

Brazil

Participant flow

Recruitment details

AUD patients of both genders were successively recruited between June of 2015 and January of 2018 from three specialized clinics for drug dependence treatment, one public and two privates, from the State of Espírito Santo, Brazil.

Participants by arm

Arm	Count
Real tDCS Ten sessions (every other day) of bilateral transcranial Direct Current Stimulation (tDCS: 2 milliamperes, 3 x 7 cm2, during 20 minutes) over dorsolateral Prefrontal Cortex (cathodal left / anodal right). 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.	23
Sham-tDCS Ten sessions (every other day) of placebo control (sham procedure) of transcranial Direct Current Stimulation (sham-tDCS) during 20 minutes with electrodes placed over the dorsolateral Prefrontal Cortex (cathodal left / anodal right). Current was delivered for 20 seconds and was turned off for the rest of the stimulation period. In this way, subjects experienced the initial itching sensation at the beginning of stimulation, but received no current for the rest of the session.	22
Total	45

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	unreliable data	1	0
Overall Study	Withdrawal by Subject	2	1

Baseline characteristics

Characteristic	Real tDCS	Sham-tDCS	Total
Age at onset of alcohol use	15.5 years STANDARD_DEVIATION 5.4	16.9 years STANDARD_DEVIATION 6	16.2 years STANDARD_DEVIATION 5.7
Age, Continuous	46.3 years STANDARD_DEVIATION 12	43.5 years STANDARD_DEVIATION 10.2	44.9 years STANDARD_DEVIATION 11.1
Amount of alcohol used (drinks/day)	20.3 drinks/day STANDARD_DEVIATION 13.4	15.5 drinks/day STANDARD_DEVIATION 15	17.9 drinks/day STANDARD_DEVIATION 14.3
Days of abstinence before study	33.0 days STANDARD_DEVIATION 12.4	32.9 days STANDARD_DEVIATION 12.5	33.0 days STANDARD_DEVIATION 12.7
Employment situation Disease benefit	3 Participants	0 Participants	3 Participants
Employment situation Formal job	2 Participants	6 Participants	8 Participants
Employment situation Freelance	2 Participants	2 Participants	4 Participants
Employment situation Informal job	2 Participants	0 Participants	2 Participants
Employment situation Not reported	1 Participants	2 Participants	3 Participants
Employment situation Retired	2 Participants	2 Participants	4 Participants
Employment situation Unemployed	11 Participants	10 Participants	21 Participants
Marital state Divorced	0 Participants	6 Participants	6 Participants
Marital state Married or common-law	7 Participants	7 Participants	14 Participants
Marital state Not reported	0 Participants	1 Participants	1 Participants
Marital state Single	15 Participants	7 Participants	22 Participants
Marital state Widow	1 Participants	1 Participants	2 Participants
Race/Ethnicity, Customized Race Black	4 Participants	4 Participants	8 Participants
Race/Ethnicity, Customized Race Brown	8 Participants	6 Participants	14 Participants
Race/Ethnicity, Customized Race White	11 Participants	12 Participants	23 Participants
Sex: Female, Male Female	5 Participants	3 Participants	8 Participants
Sex: Female, Male Male	18 Participants	19 Participants	37 Participants
Tobacco use No	11 Participants	11 Participants	22 Participants
Tobacco use Yes	12 Participants	11 Participants	23 Participants
Years of education Above 13	3 Participants	4 Participants	7 Participants
Years of education Between 10 to 13	5 Participants	5 Participants	10 Participants
Years of education Between 6 to 9	1 Participants	4 Participants	5 Participants
Years of education Not reported	1 Participants	0 Participants	1 Participants
Years of education Up to 5	13 Participants	9 Participants	22 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	0 / 23	0 / 22
other Total, other adverse events	16 / 23	13 / 22
serious Total, serious adverse events	0 / 23	0 / 22

Outcome results

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.

Time frame: 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.

Arm	Measure	Group	Value (MEAN)	Dispersion
Real tDCS	Craving	Initial scores (1st week)	5.522 scores	Standard Deviation 4.44
Real tDCS	Craving	During treatment (4th week)	1.739 scores	Standard Deviation 2.544
Real tDCS	Craving	During treatment (3rd week)	3.348 scores	Standard Deviation 3.485
Real tDCS	Craving	Final scores (5th week)	1.565 scores	Standard Deviation 2.409
Real tDCS	Craving	During treatment (2nd week)	4.391 scores	Standard Deviation 3.751
Sham-tDCS	Craving	Final scores (5th week)	2.455 scores	Standard Deviation 3.674
Sham-tDCS	Craving	Initial scores (1st week)	3.818 scores	Standard Deviation 4.468
Sham-tDCS	Craving	During treatment (2nd week)	4.136 scores	Standard Deviation 4.549
Sham-tDCS	Craving	During treatment (3rd week)	3.545 scores	Standard Deviation 3.961
Sham-tDCS	Craving	During treatment (4th week)	3.273 scores	Standard Deviation 4.322

p-value: <0.01ANOVA

Comparison: Additional comparisons between initial and final OCDS scores were done by paired t tests for each group, and differences between final and initial scores were compared between sham-tDCS and tDCS groups with unpaired t tests.p-value: <0.05t-test, 2 sided

Other Pre-specified

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.