Bilateral Prefrontal Modulation in Crack-cocaine Addiction

NCT02091167 | Completed Phase 2 Results

• 2 other identifiers: tDCS CRACK CEP_UFES 384281CNPq_ 475232/2013-5
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 1

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.

Conditions

Drug Addiction; Executive Dysfunction

Keywords

crack-cocaine addiction; tDCS; dlPFC; craving; cognition

Outcome Measures

Primary Outcomes (2)

• 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.

• 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

Study Arms (2)

real tDCS

EXPERIMENTAL

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

sham-tDCS

SHAM COMPARATOR

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

Interventions

transcranial Direct Current Stimulation 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.

Also known as: tDCS

real tDCS; sham-tDCS

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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;

Sponsors & Collaborators

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

Study Sites (1)

Federal University of Espírito Santo

Vitória, ES - Espírito Santo, 29060-720, Brazil

Location

Related Publications (12)

• 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.

  PMID: 24139147 BACKGROUND

• 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.

  PMID: 23891741 BACKGROUND

• 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.

  PMID: 24256621 BACKGROUND

• 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.

  PMID: 22878259 BACKGROUND

• 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.

  PMID: 26065432 BACKGROUND

• 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.

  PMID: 27138429 BACKGROUND

• 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.

  PMID: 30018558 BACKGROUND

• 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.

  PMID: 30050442 BACKGROUND

• 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.

  PMID: 25008145 BACKGROUND

• 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.

  PMID: 30405417 BACKGROUND

• 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.

  PMID: 30654123 BACKGROUND

• 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.

  PMID: 30405414 RESULT

MeSH Terms

Conditions

Substance-Related Disorders

Interventions

Transcranial Direct Current Stimulation

Condition Hierarchy (Ancestors)

Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Electric Stimulation Therapy; Therapeutics; Convulsive Therapy; Psychiatric Somatic Therapies; Behavioral Disciplines and Activities; Electroshock; Psychological Techniques

Limitations and Caveats

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

Results Point of Contact

• Title: Dr. Ester Miyuki Nakamura-Palacios, Coordinator of Clinical Trials
• Organization: Federal University of Espírito Santo

emnpalacios@gmail.com

+55 27 3335-7337

Study Officials

• Ester MN Palacios, MD, PhD

  Federal University of Espírito Santo

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, PhD

Model Details: Sham-controlled double-blind randomized clinical trial

Study Record Dates

• First Submitted: March 16, 2014
• First Posted: March 19, 2014
• Study Start: November 1, 2013
• Primary Completion: July 1, 2018
• Study Completion: July 1, 2018
• Last Updated: June 24, 2019
• Results First Posted: June 24, 2019

Record last verified: 2019-03

Data Sharing

• IPD Sharing: Will not share

Locations

BR (1)