Bilateral Prefrontal Modulation in Crack-cocaine Addiction

NCT ID: NCT02091167

Last Updated: 2019-06-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 33 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-11-30
• Study Completion Date: 2018-07-31

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.

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.

Conditions

Drug Addiction; Executive Dysfunction

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

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).

Group Type: EXPERIMENTAL

transcranial Direct Current Stimulation

Intervention Type: DEVICE

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.

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.

Group Type: SHAM_COMPARATOR

transcranial Direct Current Stimulation

Intervention Type: DEVICE

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.

Interventions

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.

Intervention Type: DEVICE

Other Intervention Names

tDCS

Eligibility Criteria

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;

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Conselho Nacional de Desenvolvimento Científico e Tecnológico

OTHER_GOV

Sponsor Role: collaborator

Harvard Medical School (HMS and HSDM)

OTHER

Sponsor Role: collaborator

University of Göttingen

OTHER

Sponsor Role: collaborator

Federal University of Espirito Santo

OTHER

Sponsor Role: lead

Responsible Party

Ester Miyuki Nakamura-Palacios

MD, PhD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Ester MN Palacios, MD, PhD

Role: STUDY_DIRECTOR

Federal University of Espírito Santo

Locations

Federal University of Espírito Santo

Vitória, ES - Espírito Santo, Brazil

Countries

Brazil

References

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.

Reference Type: BACKGROUND

PMID: 24139147 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 23891741 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 24256621 (View on PubMed)

de Souza Custodio 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.

Reference Type: BACKGROUND

PMID: 22878259 (View on PubMed)

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):pyv066. doi: 10.1093/ijnp/pyv066.

Reference Type: BACKGROUND

PMID: 26065432 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 27138429 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 30018558 (View on PubMed)

de Souza Custodio 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.

Reference Type: BACKGROUND

PMID: 30050442 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 25008145 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 30405417 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 30654123 (View on PubMed)

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 Users. Front Pharmacol. 2018 Oct 23;9:1198. doi: 10.3389/fphar.2018.01198. eCollection 2018.

Reference Type: RESULT

PMID: 30405414 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

CNPq_ 475232/2013-5

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

tDCS CRACK CEP_UFES 384281

Identifier Type: -

Identifier Source: org_study_id