tDCS to Reduce Craving in Cocaine Addiction- Phase 2 Study

Study Overview
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Brief Summary
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Transcranial direct current stimulation (tDCS) is a form of non-invasive brain stimulation in which low level electrical currents are applied to the scalp in order to alter brain function. In a prior Phase-I study, the research team demonstrated feasibility of self-administration of a home-tDCS prototype in 14 patients that applied 15 sessions for each patient at an outpatient center.

Detailed Description
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The ultimate goal of this project is to develop a portable neuromodulatory intervention to reduce craving in cocaine addiction. This proposed project is in response to NIH/NIDA's solicitation titled Development of Portable Neuromodulatory Device for the Treatment of Substance Use Disorders (SUDs). The present study aims to increase the efficacy of repeated administration of tDCS to reduce drug craving in individuals with cocaine addiction. Substance use disorders present a treatment challenge for clinicians, as well as a socioeconomic burden on individuals and society at large. Cocaine use disorder occurs when someone experiences clinically significant impairment caused by the recurrent use of cocaine, including health problems, physical withdrawal with discontinuation of use, persistent/escalating use, and failure to meet major personal, occupational, or educational responsibilities. At present, no FDA approved medicines are available to treat cocaine dependence, and behavioral therapy may be used to treat this addiction, though with limited efficacy. Drug craving (strong obsessions about and/or irresistible urges or compulsions to consume a drug) is a central driving force for perpetuation of substance use and subsequent addiction, as well as relapse after abstinence. Currently, no treatments exist that are targeted at reducing drug craving, which is intrusive and distressing to patients. The prefrontal cortex (PFC) plays an important role inhibiting these intrusive cravings. However, decades of data have shown that PFC activity is impaired in addictions. In this study, our goal is to increase PFC activity with non-invasive neuromodulation. Given the role of the PFC in the processing and regulation of craving behavior, this brain region is a key target for brain stimulation. This study will recruit individuals with a diagnosis of cocaine use disorder (per DSM-5 criteria) who are receiving treatment for their substance use disorder at Samaritan Daytop Village (SDV) and other similar treatment facilities (e.g., Phoenix House, Mount Sinai's network of hospitals and clinics). Patients will be randomly assigned into three groups: active (real-tDCS), real-tDCS and Cognitive Reappraisal (CR), or sham (placebo) tDCS. Participants will receive 20 minutes of stimulation per tDCS day, three days per week for five weeks. Interviews and neuropsychological testing will be conducted, and self-reported drug craving and addiction severity questionnaires will be used. Follow up cognitive and behavioral assessments will be conducted over a period of 12 months post tDCS stimulation. In addition, participants will be asked to perform EEG, cognitive tasks, and collection of a blood sample to assess genetic/epigenetic patterns

Official Title
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A Phase 2 Study to Investigate Use of Transcranial Direct Current Stimulation (tDCS) to Reduce Craving in Cocaine Addiction

Conditions
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Cocaine Use Disorder, Cocaine Dependence

Intervention / Treatment
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* Device: transcranial direct current stimulator (tDCS)
* Behavioral: Cognitive Reappraisal


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: DSM-5 diagnosis of cocaine use disorder Ability to understand the risks/benefits of the study, provide informed consent and perform tasks as per protocol English speaking For females of childbearing capacity, current use of a medically acceptable form of birth control Exclusion Criteria: Current or past history of a major neurological disorder (e.g. mental retardation, Parkinson's disease, Lewy body disease, Huntington's disease, MS, ALS, stroke, delirium tremens) or seizures, including those symptoms associated with periods of cocaine withdrawal or abstinence History of Axis I disorder, other than substance use disorder, that is associated with psychotic symptoms (e.g. schizophrenia) or neurodevelopmental disorder (e.g., autism) Use of medications (current or in the past 6 months) with known CNS effects or which may alter cerebral function, except psychotropics for depression/anxiety/PTSD (e.g. SSRIs) Clinically significant unstable medical illness or infection (e.g. HIV, hepatitis, etc.) Presence of contraindicated metallic implants or devices which may be impacted by electrical stimulation (e.g. cardiac pacemaker/defibrillator, medication pump, cochlear implant, implanted brain stimulator) Head trauma with loss of consciousness for more than 30 minutes Pregnancy or breast feeding

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Active tDCS<br>Active Transcranial Direct Current Stimulation (tDCS), (Soterix Medical mini-CT tDCS stimulator) | Device: transcranial direct current stimulator (tDCS)<br>* Patients will have two electrodes applied (one anode, one cathode) administering active (real) or sham (placebo, not real) tDCS stimulation. Stimulation will last 20 minutes per day, three days per week, for 5 weeks<br>* Other names: Soterix Medical mini-CT tDCS stimulator;|
| Sham Comparator: Sham tDCS<br>Sham (Placebo) Transcranial Direct Current Stimulation (tDCS), Soterix Medical mini-CT tDCS stimulator | Device: transcranial direct current stimulator (tDCS)<br>* Patients will have two electrodes applied (one anode, one cathode) administering active (real) or sham (placebo, not real) tDCS stimulation. Stimulation will last 20 minutes per day, three days per week, for 5 weeks<br>* Other names: Soterix Medical mini-CT tDCS stimulator;|
| Experimental: Active tDCS with Cognitive Reappraisal (CR)<br>Active Transcranial Direct Current Stimulation (tDCS) (Soterix Medical mini-CT tDCS stimulator), and Cognitive Reappraisal (CR) | Device: transcranial direct current stimulator (tDCS)<br>* Patients will have two electrodes applied (one anode, one cathode) administering active (real) or sham (placebo, not real) tDCS stimulation. Stimulation will last 20 minutes per day, three days per week, for 5 weeks<br>* Other names: Soterix Medical mini-CT tDCS stimulator;Behavioral: Cognitive Reappraisal<br>* Emotion regulation therapy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Cocaine Craving from Baseline (Obsessive-Compulsive Cocaine Scale score) | Craving for cocaine will be assessed with a brief scale composed of 5 items (1, 2, 4, 5, and 13) from the Obsessive-Compulsive Cocaine Scale (OCCS; Vorspan et al., 2012). | Baseline (pre-tDCS), post-tDCS sessions (approx. week 6), Follow-up (1 month, 3 month) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Depression symptoms from Baseline (Ham-D score) | Depression symptoms will be assessed by the Hamilton Rating Scale for Depression (24 item version, HAM-D; Hamilton, 1960). | Baseline (pre-tDCS), post-tDCS sessions (approx. week 6), Follow-up (1 month, 3 month) | 
| Change in Anxiety symptoms from Baseline (HAM-A score) | Anxiety symptoms will be assessed by the Hamilton Rating Scale for Anxiety (HAM-A; Hamilton, 1959). | Baseline (pre-tDCS), post-tDCS sessions (approx. week 6), Follow-up (1 month, 3 month) | 
| Change in Quality of Life from Baseline (WHOQOL-BREF score) | An abbreviated instrument of cross-culturally valid assessment of quality of life of the World Health Organization (WHOQOL-BREF) with 26 questions (WHOQOL Group, 1998; Skevington et al., 2004) yields 4 domains (physical health, psychological, social relationships, and environment) and 2 individually scored items regarding overall perception of quality of life (Q1) and health (Q2). The 4 domain scores are scaled in a way that higher scores stand for higher quality of life. | Baseline (pre-tDCS), post-tDCS sessions (approx. week 6), Follow-up (1 month, 3 month) | 
| EEG Late Positive Potential from Baseline | The Late Positive Potential (LLP), also known as the Late Positive Wave, is an Event Related Potential (ERP) that is formed approximately 400 ms after exposure to a stimulus and continues until about 2 s after the exposure. Higher LPP amplitude has been shown to indicate a higher level of cocaine craving (Parvaz 2016). We will present images of cocaine-related tasks to subjects and measure the amplitude of the LPP using a 64-electrode EEG cap. We will compare the LPP amplitude at each testing session to baseline amplitude. | Baseline (pre-tDCS), post-tDCS sessions (approx. week 6), Follow-up (1 month, 3 month) | 
| Urine Test Analysis from Baseline | Testing for the presence of cocaine in urine samples | Baseline (pre-tDCS), post-tDCS sessions (approx. week 6), Follow-up (1 month, 3 month) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Transcranial Direct Current Stimulation, tDCS, Brain Stimulation, Cocaine Addiction, Drug Craving