tDCS and Cognitive Training Intervention for Chronic Smokers With Schizophrenia

Study Overview
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Brief Summary
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This study is being done to develop new methods to help smokers with schizophrenia to successfully reduce their smoking and/or quit. This is not a treatment study, but will help find new techniques to create better treatments. Specifically, the investigators are interested in learning more about how thoughts and attention problems associated with schizophrenia might play a role in smoking, as well as the impact of cognitive (thinking, reasoning, and remembering) training and brain stimulation on these symptoms and on actual smoking.

Detailed Description
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Adults with severe mental illness (SMI) are three times more likely to smoke than non-SMI adults, consuming 35-44% of all cigarettes in the U.S.; and, the highest rates of tobacco-related illnesses and death are among smokers with schizophrenia. Unfortunately, not only are patients with schizophrenia less likely to receive smoking treatments, but cessation medications are only modestly effective in helping this subset of smokers quit. Therefore, it is vital to discover new treatment adjuncts that specifically aid this high-risk subset of smokers to achieve successful abstinence. Toward that end, the investigators propose a novel non-pharmacologic technique that directly targets both cognitive impairment, an avenue considerable past research suggests may be particularly effective to exploit in smokers with schizophrenia, and reactivity to prepotent stimuli, shown to be enhanced in smokers with schizophrenia. Combining a subset of cognitive enhancement therapy known as Cognitive Remediation (CR), with another safe and effective technique, Transcranial Direct Current Stimulation (tDCS), the investigators propose a new cognitive training method aimed at enabling smokers with schizophrenia to gain greater control over smoking and stimuli-induced reactivity (e.g., craving). Recent studies have found significant tDCS-induced cognitive enhancement, as well as reduction in both cue-induced craving and smoking behavior among healthy smokers. This combined with knowledge of the cognitive deficits that exist among individuals with schizophrenia, and clear evidence of a relationship between cognitive function and smoking treatment success, provides the rationale for testing novel CR + tDCS to target underlying mechanisms of smoking among individuals with schizophrenia. Specifically, the proposed study will examine the extent to which targeted cognitive enhancement with CR + tDCS, leads to changes in cognitive control, cue-provoked craving, reaction time and ERP measures of attentional bias; as well as the impact of these changes on smoking behavior and intention and confidence to quit among 80 smokers with schizophrenia. The goal of this study is to inform the development of new non-medication, noninvasive, therapeutic techniques to specifically target smoking among patients with schizophrenia. The long term goal is to establish an effective treatment adjunct to help smokers with schizophrenia successfully achieve abstinence.

Official Title
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tDCS and Cognitive Training Intervention for Chronic Smokers With Schizophrenia

Conditions
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Transcranial Direct Current Stimulation, Smoking, Cigarette, Schizophrenia

Intervention / Treatment
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* Other: Transcranial Direct Current Stimulation
* Behavioral: Cognitive Remediation (CR)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Currently meets DSM-5 criteria for Schizophrenia, Schizoaffective Disorder, Schizophreniform Disorder, or Delusional Disorder. Ability to provide written informed consent Smoke ≥ 7 cigarettes per day Expired breath CO ≥ 10 ppm at screening Stable medication regimen for ≥ 4 weeks (If on more than one psychotropic medication, main antipsychotic will be considered for stability) Exclusion Criteria: Epilepsy or Current Seizure Disorder Alcohol or Substance Dependence past 3 months (caffeine allowed, nicotine is part of inclusion criteria). Pregnant or lactating Psychiatric hospitalization in past 3 months Suicidal and/or aggressive behavior past 3 months Implanted cardiac or brain medical devices Latex allergy Scalp irritation or recent shaving of scalp Use of other smoking cessation medication History of head trauma History of ECT

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: Factorial Assignment
Interventional Model Description: 2 (CR, Control CR) x 2 (tDCS xSham tDCS)
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CR + tDCS<br>Cognitive Remediation (CR) and Transcranial Direct Current Stimulation (tDCS) | Other: Transcranial Direct Current Stimulation<br>* Transcranial direct current stimulation targeting the right inferior frontal gyrus<br>* Other names: tDCS;Behavioral: Cognitive Remediation (CR)<br>* Cognitive exercises on a computer designed to increase attention, memory, and processing speed.<br>|
| Sham Comparator: CR + sham tDCS<br>Cognitive Remediation (CR) and Sham Transcranial Direct Current Stimulation (tDCS) | Behavioral: Cognitive Remediation (CR)<br>* Cognitive exercises on a computer designed to increase attention, memory, and processing speed.<br>|
| Sham Comparator: control CR + tDCS<br>Control Cognitive Remediation (CR) and Transcranial Direct Current Stimulation (tDCS) | Other: Transcranial Direct Current Stimulation<br>* Transcranial direct current stimulation targeting the right inferior frontal gyrus<br>* Other names: tDCS;|
| No Intervention: control CR + sham tDCS<br>Control Cognitive Remediation (CR) and Sham Transcranial Direct Current Stimulation (tDCS) | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS™): MATRICS Consensus Cognitive Battery (MCCB) | the MATRICS Consensus battery (MCCB) is a cognitive battery of tests for assessing cognition-enhancing treatments for schizophrenia through a broadly based scientific evaluation of measures. Change in cognitive measures of MATRICS Consensus Cognitive Battery (MCCB). Post-intervention minus baseline. Scale is scored 0-100. Difference score range is (-100 to 100) with positive scores reflecting improvement. | Baseline to approximately 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cue-Reactivity | Change in cue-induced craving indexed as change in self-report craving on the questionnaire of smoking urges, 4-item version (QSU-4) from baseline to end of intervention. Craving rating range = 0-100. Difference scores range from (-100 to 100) with a negative score reflecting improvement. | Baseline to approximately 4 weeks | 
| Cigarette Puff Volume | Change in mean cigarette puff volume | Baseline and at approximately 4 weeks | 
| Latency to First Cigarette Puff | Change in mean latency to first cigarette puff | Baseline to approximately 4 weeks | 
| AX Version of the Continuous Performance Task (AX-CPT) Reaction Time | AX version of the CPT measures a participant's active maintenance and cognitive control. In this task, the participant is presented with a series of trials in which they are instructed to make a response which distinguishes between stimuli. Here the stimuli included are: smoking, nonsmoking, person, non-person). Assessment is of Post - Pre intervention difference in reaction time to respond to stimuli on the AX Version of the Continuous Performance Task (AX-CPT) | Baseline to approximately 4 weeks | 
| AX Version of the Continuous Performance Task (AX-CPT) Reaction Time Variability | Post minus pre-intervention difference Reaction time variability for hits on the AX Version of the Continuous Performance Task (AX-CPT). A negative value indicates improvement. | Baseline to approximately 4 weeks | 
| EEG (Electroencephalogram) N170 Amplitude | Difference in change scores (post minus pre-intervention) in N170 Amplitude between smoking and neutral images. A more negative score indicates greater improvement. | Baseline to approximately 4 weeks | 
| EEG (Electroencephalogram) Contingent Negative Variation (CNV) | Difference in CNV between the A and X in the AX-CPT Task. More negative indicates larger CNV. | Baseline to approximately 4 weeks | 
| EEG (Electroencephalogram) Beta-Band Event-Related Desynchronization (ERD) | Difference in ERD between the A and X in AX-CPT during EEG assessment of Beta-Band Event-Related Desynchronization (ERD). More negative values indicate greater Beta-band ERD at post-intervention. | Baseline to approximately 4 weeks | 
| Attention & Smoking Cue Exposure Task (ASCET) | Post minus Pre-intervention difference in Reaction time between smoking and neutral images presented with the ASCET task. A negative RT indicates improvement. | Baseline to approximately 4 weeks | 
| Total Number of Puffs | Change in number of puffs on cigarettes assessment during smoking topography measurement during the cue reactivity task. Number of puffs was assessed during pre-training cue reactivity and again during post-training cue reactivity. | Baseline to approximately 4 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Transcranial Direct Current Stimulation, Smoking, Schizophrenia