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tDCS_CRACK: Bilateral Prefrontal Modulation in Crack-cocaine Addiction

Sponsor
Federal University of Espirito Santo (Other)
Overall Status
Completed
CT.gov ID
NCT02091167
Collaborator
Conselho Nacional de Desenvolvimento Científico e Tecnológico (Other), Harvard Medical School (HMS and HSDM) (Other), University of Göttingen (Other)
33
Enrollment
1
Location
2
Arms
56
Actual Duration (Months)
0.6
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

In this study, eligible crack-cocaine addicted inpatients recruited from specialized clinics for substance abuse disorder 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, 3x7 cm2, for 20 min) or placebo (sham-tDCS). Craving to the use of crack-cocaine 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 clinical, cognitive and brain function in crack-cocaine addiction and these would be long-lasting effects.

Condition or Disease Intervention/Treatment Phase
  • Device: transcranial Direct Current Stimulation
 Phase 2

Detailed Description

Before (baseline) and after tDCS or sham-tDCS treatment, subjects were examined:

(1) clinically, regarding craving (obsessive compulsive scale) and relapses to the drug use.

They were followed-up for clinical examination at least 60 days after treatment.

Study Design

Study Type:
Interventional
Actual Enrollment :
33 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Intervention Model Description:
Sham-controlled double-blind randomized clinical trialSham-controlled double-blind randomized clinical trial
Masking:
Triple (Participant, Care Provider, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
Prefrontal Modulation by Repetitive Bilateral Transcranial Direct Current Stimulation (tDCS) in Crack-cocaine Addicted Inpatients.
Actual Study Start Date :
Nov 1, 2013
Actual Primary Completion Date :
Jul 1, 2018
Actual Study Completion Date :
Jul 1, 2018

Arms and Interventions

Arm Intervention/Treatment
Experimental: 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).

Device: transcranial Direct Current Stimulation
Direct currents are 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 is delivered by an electric stimulator. To stimulate the left DLPFC, the cathode electrode is placed over F3 according to the 10-20 international system while the anode is placed over the contralateral F4 region. The currents flows continuously for 20 minutes with an intensity of 2 milliamperes.
Other Names:
  • tDCS

    		•
    Sham Comparator: 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 30 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.

    Device: transcranial Direct Current Stimulation
    Direct currents are 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 is delivered by an electric stimulator. To stimulate the left DLPFC, the cathode electrode is placed over F3 according to the 10-20 international system while the anode is placed over the contralateral F4 region. The currents flows continuously for 20 minutes with an intensity of 2 milliamperes.
    Other Names:
  • tDCS

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Craving [Five applications: once in the week before tDCS treatment (baseline), second, third and fourth weeks, during the treatment, and in the fith 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.

    2. Relapses [30 and 60 days after discharge from clinics]

      A use relapse was defined as the first episode of return to the previous uncontrolled pattern of crack-cocaine use (rocks per day). Information about relapse were gathered directly when patients regularly returned to the hospital for clinical follow-up after their discharge and/or by self-report or reports of family members by telephone calls.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 60 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    Yes
    Inclusion Criteria:

    • patients between the age of 18 and 60 years;

    • met criteria for crack-cocaine dependence according to the Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5), 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 than crack-cocaine;

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

    • a diagnosis of epilepsy, convulsions;

    • 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;

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Federal University of Espírito Santo Vitória ES - Espírito Santo Brazil 29060-720

    Sponsors and Collaborators

    • Federal University of Espirito Santo
    • Conselho Nacional de Desenvolvimento Científico e Tecnológico
    • Harvard Medical School (HMS and HSDM)
    • University of Göttingen

    Investigators

    • Study Director: Ester MN Palacios, MD, PhD, Federal University of Espírito Santo

    Study Documents (Full-Text)

    More Information

    Publications

    Responsible Party:
    Ester Miyuki Nakamura-Palacios, MD, PhD, Federal University of Espirito Santo
    ClinicalTrials.gov Identifier:
    NCT02091167
    Other Study ID Numbers:
    • tDCS CRACK CEP_UFES 384281
    • CNPq_ 475232/2013-5
    First Posted:
    Mar 19, 2014
    Last Update Posted:
    Jun 24, 2019
    Last Verified:
    Mar 1, 2019
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Keywords provided by Ester Miyuki Nakamura-Palacios, MD, PhD, Federal University of Espirito Santo
    crack-cocaine addiction
    tDCS
    dlPFC
    craving
    cognition
    Additional relevant MeSH terms:
    Substance-Related Disorders
    Behavior, Addictive

    Study Results

    Participant Flow

    Recruitment Details There were two dropouts in the sham-tDCS group that were excluded after randomization. One patient escaped from the treatment facility and the other had to be discontinued because of precocious discharge from the clinic for misconduct.
    Pre-assignment Detail
    Arm/Group Title Real tDCS Sham-tDCS
    Arm/Group Description 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 are 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 is delivered by an electric stimulator. To stimulate the left DLPFC, the cathode electrode is placed over F3 according to the 10-20 international system while the anode is placed over the contralateral F4 region. The currents flows continuously for 20 minutes with an intensity of 2 milliamperes. 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 30 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. transcranial Direct Current Stimulation: Direct currents are 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 is delivered by an electric stimulator. To stimulate the left DLPFC, the cathode electrode is placed over F3 according to the 10-20 international system while the anode is placed over the contralateral F4 region. The currents flows continuously for 20 minutes with an intensity of 2 milliamperes.
    Period Title: Overall Study
    STARTED 19 16
    COMPLETED 19 14
    NOT COMPLETED 0 2

    Baseline Characteristics

    Arm/Group Title Real tDCS Sham-tDCS Total
    Arm/Group Description 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 are 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 is delivered by an electric stimulator. To stimulate the left DLPFC, the cathode electrode is placed over F3 according to the 10-20 international system while the anode is placed over the contralateral F4 region. The currents flows continuously for 20 minutes with an intensity of 2 milliamperes. 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 30 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. transcranial Direct Current Stimulation: Direct currents are 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 is delivered by an electric stimulator. To stimulate the left DLPFC, the cathode electrode is placed over F3 according to the 10-20 international system while the anode is placed over the contralateral F4 region. The currents flows continuously for 20 minutes with an intensity of 2 milliamperes. Total of all reporting groups
    Overall Participants 19 14 33
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    35.1
    (9.6)
    35.0
    (8.2)
    35.03
    (8.7)
    Sex: Female, Male (Count of Participants)
    Female
    4
    21.1%
    2
    14.3%
    6
    18.2%
    Male
    15
    78.9%
    12
    85.7%
    27
    81.8%
    Race and Ethnicity Not Collected (Count of Participants)
    Count of Participants [Participants]
    0
    0%
    Years of education (Count of Participants)
    Between 6 to 9
    7
    36.8%
    4
    28.6%
    11
    33.3%
    Between 10 to 13
    8
    42.1%
    7
    50%
    15
    45.5%
    Above 13
    4
    21.1%
    3
    21.4%
    7
    21.2%
    Employment situation (Count of Participants)
    Formal job
    2
    10.5%
    4
    28.6%
    6
    18.2%
    Unemployed
    9
    47.4%
    8
    57.1%
    17
    51.5%
    Freelance
    7
    36.8%
    1
    7.1%
    8
    24.2%
    Retired
    1
    5.3%
    1
    7.1%
    2
    6.1%
    Marital state (Count of Participants)
    Single
    12
    63.2%
    10
    71.4%
    22
    66.7%
    Married
    2
    10.5%
    0
    0%
    2
    6.1%
    Common-law
    0
    0%
    1
    7.1%
    1
    3%
    Divorced
    1
    5.3%
    2
    14.3%
    3
    9.1%
    Widow
    0
    0%
    1
    7.1%
    1
    3%
    Non reported
    4
    21.1%
    0
    0%
    4
    12.1%
    Tobacco use (Count of Participants)
    Yes
    11
    57.9%
    11
    78.6%
    22
    66.7%
    No
    8
    42.1%
    3
    21.4%
    11
    33.3%

    Outcome Measures

    1. Primary Outcome
    Title Craving
    Description 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: once in the week before tDCS treatment (baseline), second, third and fourth weeks, during the treatment, and in the fith week, after the end of the tDCS treatment.

    Outcome Measure Data

    Analysis Population Description
    Two patients from each group were lost to follow-up after their discharge from the hospital.
    Arm/Group Title Real-tDCS Sham-tDCS
    Arm/Group Description Crack-cocaine patients who underwent 10 sessions of real tDCS treatment. Crack-cocaine patients who underwent sham (placebo)-tDCS control procedure.
    Measure Participants 19 14
    1
    6.53
    (5.2)
    7.0
    (3.8)
    2
    4.74
    (4.1)
    4.43
    (2.9)
    3
    3.63
    (3.9)
    4.0
    (3.2)
    4
    2.63
    (3.4)
    3.5
    (3.1)
    5
    2.26
    (2.9)
    4.07
    (3.4)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Real-tDCS, Sham-tDCS
    Comments We powered for a medium effect size based on our previous study with effect size (partial ղ2) of 0.10384 for the main within-subject factor in the two-way ANOVA with repeated measures. With a power of 80%, and a two-sided probability of a type I error of 5%, the resulting minimum sample size was 30 participants. To account for waiving or dropouts we increased the estimated sample size to approximately 10%, resulting in 33 subjects in total (approximately 16 to 17 subjects in each group).
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value 0.05
    Comments
    Method ANOVA
    Comments
    Other Statistical Analysis Most of data (age, patterns of crack-cocaine use, 5-items OCCS) were normally distributed according to the D'Agostino & Pearson normality test, thus they were analyzed by parametric tests. Between-group (sham- and real tDCS) comparisons were conducted by unpaired Student´s t-tests. For all other non-parametric data (gender, schooling, employment, marital state and tobacco use), Chi-square or Fisher tests were used to compare sham and real tDCS groups. Besides the two-way ANOVA with repeated measures followed by Bonferroni-corrected t-tests, linear regression analyses were done over craving scores obtained along the 4-week treatment (five time-points measurements) for both groups. 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 real tDCS groups with unpaired t-test.
    2. Primary Outcome
    Title Relapses
    Description A use relapse was defined as the first episode of return to the previous uncontrolled pattern of crack-cocaine use (rocks per day). Information about relapse were gathered directly when patients regularly returned to the hospital for clinical follow-up after their discharge and/or by self-report or reports of family members by telephone calls.
    Time Frame 30 and 60 days after discharge from clinics

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Real-tDCS Sham-tDCS
    Arm/Group Description Crack-cocaine patients who underwent 10 sessions of real tDCS treatment. Crack-cocaine patients who underwent sham (placebo)-tDCS control procedure.
    Measure Participants 17 12
    Not relapsed
    10
    52.6%
    7
    50%
    Relapsed
    7
    36.8%
    5
    35.7%
    Not relapsed
    8
    42.1%
    4
    28.6%
    Relapsed
    9
    47.4%
    8
    57.1%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Real-tDCS, Sham-tDCS
    Comments Two patients from each group were lost to follow-up after their discharge from the hospital.
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value 0.05
    Comments
    Method Fisher Exact
    Comments

    Adverse Events

    Time Frame Adverse events were examined once at the end of each tDCS application. Therefore, over 10 tDCS applications, with a total of 10 examinations.
    Adverse Event Reporting Description We asked subjects about the following adverse effects: headache, neck and scalp pain, tingling, itching, skin redness, burning sensation of the scalp, sleepiness, acute mood changes, trouble concentrating, and others after treatment.
    Arm/Group Title Real-tDCS Sham-tDCS
    Arm/Group Description Crack-cocaine patients who underwent 10 sessions of real tDCS treatment. Crack-cocaine patients who underwent sham (placebo)-tDCS control procedure.
    All Cause Mortality
    Real-tDCS Sham-tDCS
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/19 (0%) 2/14 (14.3%)
    Serious Adverse Events
    Real-tDCS Sham-tDCS
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/19 (0%) 0/14 (0%)
    Other (Not Including Serious) Adverse Events
    Real-tDCS Sham-tDCS
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 16/19 (84.2%) 8/14 (57.1%)
    Nervous system disorders
    Headache 0/19 (0%) 0 1/14 (7.1%) 1
    Drowsiness 1/19 (5.3%) 1 0/14 (0%) 0
    Skin and subcutaneous tissue disorders
    Tingling in the scalp 14/19 (73.7%) 14 7/14 (50%) 7
    Burning sensation of the scalp 1/19 (5.3%) 1 0/14 (0%) 0

    Limitations/Caveats

    Sample size restricted by inclusion and exclusion criteria, limiting generalizability of our results.

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/Title Dr. Ester Miyuki Nakamura-Palacios, Coordinator of Clinical Trials
    Organization Federal University of Espírito Santo
    Phone +55 27 3335-7337
    Email emnpalacios@gmail.com
    Responsible Party:
    Ester Miyuki Nakamura-Palacios, MD, PhD, Federal University of Espirito Santo
    ClinicalTrials.gov Identifier:
    NCT02091167
    Other Study ID Numbers:
    • tDCS CRACK CEP_UFES 384281
    • CNPq_ 475232/2013-5
    First Posted:
    Mar 19, 2014
    Last Update Posted:
    Jun 24, 2019
    Last Verified:
    Mar 1, 2019