Bilateral Prefrontal Modulation in Crack-cocaine Addiction

Executive Dysfunction Clinical Trial

— tDCS_CRACK  

Official title:

Prefrontal Modulation by Repetitive Bilateral Transcranial Direct Current Stimulation (tDCS) in Crack-cocaine Addicted Inpatients.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02091167
• Other study ID #: tDCS CRACK CEP_UFES 384281
• Secondary ID: CNPq_ 475232/201
• Status: Completed
• Phase: Phase 2
• Start date: November 2013
• Est. completion date: July 2018

Study information

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

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 33
• Est. completion date: July 2018
• Est. primary completion date: July 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 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;

Related Conditions & MeSH terms

• Behavior, Addictive
• Cocaine-Related Disorders
• Drug Addiction
• Executive Dysfunction
• Substance-Related Disorders

Intervention

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.

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 (12)

Anders QS, Klauss J, Rodrigues LCM, Nakamura-Palacios EM. FosB mRNA Expression in Peripheral Blood Lymphocytes in Drug Addicted Patients. Front Pharmacol. 2018 Oct 24;9:1205. doi: 10.3389/fphar.2018.01205. eCollection 2018. — View Citation

Batista EK, Klauss J, Fregni F, Nitsche MA, Nakamura-Palacios EM. A Randomized Placebo-Controlled Trial of Targeted Prefrontal Cortex Modulation with Bilateral tDCS in Patients with Crack-Cocaine Dependence. Int J Neuropsychopharmacol. 2015 Jun 10;18(12). pii: pyv066. doi: 10.1093/ijnp/pyv066. — View Citation

Conti CL, Nakamura-Palacios EM. Bilateral transcranial direct current stimulation over dorsolateral prefrontal cortex changes the drug-cued reactivity in the anterior cingulate cortex of crack-cocaine addicts. Brain Stimul. 2014 Jan-Feb;7(1):130-2. doi: 10.1016/j.brs.2013.09.007. Epub 2013 Oct 12. — View Citation

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

de Souza Custódio JC, Martins CW, Lugon MD, Fregni F, Nakamura-Palacios EM. Epidural direct current stimulation over the left medial prefrontal cortex facilitates spatial working memory performance in rats. Brain Stimul. 2013 May;6(3):261-9. doi: 10.1016/j.brs.2012.07.004. Epub 2012 Aug 1. — View Citation

de Souza Custódio JC, Martins CW, Lugon MDMV, de Melo Rodrigues LC, de Figueiredo SG, Nakamura-Palacios EM. Prefrontal BDNF Levels After Anodal Epidural Direct Current Stimulation in Rats. Front Pharmacol. 2018 Jul 12;9:755. doi: 10.3389/fphar.2018.00755. eCollection 2018. — View Citation

Klauss J, Anders QS, Felippe LV, Ferreira LVB, Cruz MA, Nitsche MA, Nakamura-Palacios EM. Lack of Effects of Extended Sessions of Transcranial Direct Current Stimulation (tDCS) Over Dorsolateral Prefrontal Cortex on Craving and Relapses in Crack-Cocaine U — 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 Pharmacol. 2018 Jul 3;9:716. doi: 10.3389/fphar.2018.00716. eCollection 2018. — 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

Martins CW, de Melo Rodrigues LC, Nitsche MA, Nakamura-Palacios EM. AMPA receptors are involved in prefrontal direct current stimulation effects on long-term working memory and GAP-43 expression. Behav Brain Res. 2019 Apr 19;362:208-212. doi: 10.1016/j.bbr.2019.01.023. Epub 2019 Jan 14. — View Citation

Nakamura-Palacios EM, Lopes IB, Souza RA, Klauss J, Batista EK, Conti CL, Moscon JA, de Souza RS. Ventral medial prefrontal cortex (vmPFC) as a target of the dorsolateral prefrontal modulation by transcranial direct current stimulation (tDCS) in drug addiction. J Neural Transm (Vienna). 2016 Oct;123(10):1179-94. doi: 10.1007/s00702-016-1559-9. Epub 2016 Apr 30. — 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

* Note: There are 12 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
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: 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.
Primary	Relapses	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.	30 and 60 days after discharge from clinics