Prefrontal Cortex Stimulation as Treatment for Crack-cocaine Addiction

Study Overview
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Brief Summary
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The use of crack-cocaine is growing at alarming rate in our country and it is absolutely worrisome the fast establishment of addiction to it. Its immediate effects, that are intense and extremely fleeting, increase dramatically the probability of this drug to be consumed again, settling quickly down the loss of control and the compulsive use, turning the effects of this drug highly addictive. Parallel to this process, brain damages are quickly established, progressing to severe impairments of frontal functions, leading to the lack of cognitive control that feeds back and aggravates the dependence, and hampers any therapeutic approach. The existing treatments have not proved to be satisfactory yet. Thus, considering that a new modality of treatment, based on the neuromodulation induced by noninvasive brain stimulation, has been useful in treating various neuropsychiatric conditions, this study will examine the potential beneficial effects of repeated transcranial Direct Current Stimulation over the left dorsolateral prefrontal cortex in the treatment of crack-cocaine addiction.

Detailed Description
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Forty subjects between 18 and 60 years old, both genders, with a diagnosis of dependence on crack-cocaine, evaluated for the first time at the Center for Psychosocial Care for Alcohol and Other Drugs (CAPS-AD, in Portuguese) in the municipality of Serra, ES, Brazil, will be invited to participate in this study. After triage, following the inclusion and exclusion criteria, they will be informed in details about the experimental protocol and, if they agree to participate, it will be required to sign an Informed Consent. It Will be applied a structured anamnesis, made a psychiatric clinical and physical examination. The treatment will be started with regular medications for abstinence and comorbidities and psychosocial approaches usually done in the CAPS-AD. After selected they will be referred to the Laboratory of Cognitive Science and Neuropsychopharmacology of the Postgraduate Program in Physiological Sciences from Health Sciences Center of Federal University of Espírito Santo where they will be semi-randomly (matched for age, gender and sociodemographic characteristics) distributed into two different groups: (A) sham-tDCS (n = 20) and (B) active-tDCS (n = 20); and they will follow for 10 applications in daily sessions, excepting on weekends, of transcranial direct current stimulation (tDCS, 5 x 7 cm2, 2 mA, 20 min) over the left dorsolateral prefrontal cortex or sham procedure. Event-related potentials (ERP) will be recorded before, during and after brain stimulation or sham procedure under random presentation of three related images and three non-related images to crack use. The compulsive behavior will be evaluated before and after the ERP records. Cognitive tests which assess mental function, frontal function, visuospatial and verbal working memory, inhibition, and conflict resolution will be performed. The depression will be assessed during the treatment, and the addicted subjects will be evaluated once a week for four consecutive weeks after a series of applications of sham-tDCS or active-tDCS.

Official Title
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Treatment of Crack-cocaine Addiction Through Cognitive Neuromodulation of the Prefrontal Cortex Produced by Transcranial Direct Current Stimulation.

Conditions
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Cocaine Addiction, Cocaine-related Disorder, Executive Dysfunction

Intervention / Treatment
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* Device: transcranial Direct Current Stimulation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: fulfill the criteria for the crack-dependence syndrome, based on criteria of the International Classification of Diseases on its 10th version; all users and addicts who make use of crack-cocaine alone or in combination with other drugs (alcohol, nicotine, caffeine, cannabis, etc.), or who have psychiatric comorbidities (anxiety, depression, etc.) must be clinically stable and not requiring hospitalization; should be clinically suitable for the treatment proposed in this study; need to be able to read, write and speak Portuguese Exclusion Criteria: should not present current or past illnesses that may be aggravated during treatment; may not show abnormalities in laboratory tests which suggest a deterioration of its physical condition for participation in the study; individuals who have some metal in the brain or skull (chips, fragments, pins, etc. - except titanium); history of epilepsy, severe brain trauma, cochlear implant, cardiac pacemaker or intracardiac metal apparatus); pregnants.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: sham-tDCS<br>the electrodes are positioned in the same manner as the active-tDCS, activated for 20 s (time to climb ramp of the current until reach the current intensity used in the experiment), enough to produce the sensation of itch, and turned off until the end of the session. | Device: transcranial Direct Current Stimulation<br>* transcranial Direct Current Stimulation (tDCS) will be applied by electrodes (5 x 7 cm2), with intensity of 2 mA, during 20 min, with cathode over the left dorsolateral prefrontal cortex (F3 site) and anode placed in the contralateral dorsolateral prefrontal cortex (F4 site).<br>* Other names: non-invasive brain stimulation;|
| Experimental: active-tDCS<br>low-intensity transcranial Direct Current Stimulation (tDCS)applied over the dorsolateral prefrontal cortex | Device: transcranial Direct Current Stimulation<br>* transcranial Direct Current Stimulation (tDCS) will be applied by electrodes (5 x 7 cm2), with intensity of 2 mA, during 20 min, with cathode over the left dorsolateral prefrontal cortex (F3 site) and anode placed in the contralateral dorsolateral prefrontal cortex (F4 site).<br>* Other names: non-invasive brain stimulation;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Abstinence | abstinence to the use of crack-cocaine up to 3 months after the completion of two-weeks of treatment sessions with active-tDCS or sham-tDCS. | Two days after the end of tDCS treatment (one session every other day, 5 sessions), that is, on the 12nd day from the beginning. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Intensity of the Urge to the Use of Crack-cocaine | The intensity of craving will be examined by a short scale, the Brief Cocaine Craving Questionnaire. | before and after ERP in two weekly sessions over two weeks | 
| Event Related Potentials | Event Related Potentials (ERPs) elicited by random presentation of three related images and three non-related images to crack use every Monday and Friday over the two-weeks period of active-tDCS or sham-tDCS. | twice a week over two consecutive weeks during the treatment | 
| Cognitive Tests | Cognitive tests are comprised by frontal assessment battery (FAB), Mini-Mental Status Examination (MMSE), verbal n-back task, visuospatial n-back task, go/no-go test. | Before the first experimental session, in the middle of the protocol and two days after the last experimental session | 
| State of Depression | It will be applied Hamilton Scale for Depression, a structured multiple choice questionnaire used to assess the severity of the symptoms of depression. It will be applied with cognitive tests. | Before the first experimental session, in the middle of the treatment and after the last experimental session. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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crack cocaine, addiction, tDCS, ERP, P300, attention, inhibitory control, working memory