tDCS Coupled With Virtual Rehabilitation for Negative Symptoms in At-Risk Youth

Study Overview
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Brief Summary
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Negative symptoms, which include the loss of motivation, social withdrawal and reduced emotional expression are prominent in youth at clinical high risk (CHR) for psychosis. These negative symptoms lead to significant functional impairment and enduring disability in these youth. At present, there are no established treatments for negative symptoms. Recent evidence from independent studies, however, suggests two promising novel treatment approaches for negative symptoms, transcranial direct current stimulation (tDCS), and computerized remediation strategies. The primary aim of this study is to evaluate if tDCS combined with a virtual reality-based computerized remediation (VR) is effective for treating negative symptoms in CHR youth, thereby mitigating the enduring functional disability these symptoms cause.

Detailed Description
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Negative symptoms, which include amotivation, social withdrawal and diminished emotional expression are prominent in youth at clinical high risk (CHR) for psychosis. Negative symptoms lead to significant functional impairment and enduring disability in these youth regardless of subsequent conversion to psychosis. At present, there are no established treatments for negative symptoms. Recent evidence from independent studies, however, suggests two promising novel treatment approaches for negative symptoms, transcranial direct current stimulation (tDCS), and computerized remediation strategies, both of which have revealed significant therapeutic effects on negative symptoms in schizophrenia (SZ). tDCS involves delivery of a low intensity continuous electrical field to the frontal cortex. tDCS is very safe and well tolerated, and is currently being investigated as a treatment for several psychiatric disorders. tDCS is also Health Canada approved for the treatment of major depressive disorder. The primary aim of this randomized controlled trial is to evaluate if tDCS combined with a virtual reality-based computerized remediation (VR), administered three times per week for four weeks, is effective for treating negative symptoms in CHR youth, thereby mitigating the enduring functional disability these symptoms cause.

Official Title
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Transcranial Direct Current Stimulation Coupled With Virtual Rehabilitation for Negative Symptoms in At-Risk Youth

Conditions
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Clinical High Risk for Psychosis

Intervention / Treatment
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* Device: Active tDCS
* Behavioral: Active VR Motivation Training
* Device: Sham tDCS
* Behavioral: Sham VR Motivation Training


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: between the ages of 16 and 30; meet CHR criteria for a psychosis risk syndrome determined by the Structured Interview for Prodromal Symptoms (SIPS); have a Scale of Prodromal Symptoms (SOPS) negative subscale (SOPS-Neg) score of > 11, with at least one negative symptom of at least moderate severity (i.e., ≥ 3) Exclusion Criteria: meet criteria for a current or lifetime psychotic disorder; have an IQ < 70; a history of seizures or clinically significant neurological disorder that may contribute to prodromal symptoms. have been involved in another treatment study in the past 4 weeks.

Ages Eligible for Study
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Minimum Age: 16 Years
Maximum Age: 30 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 + Active VR<br>Active tDCS over the left DLPFC (30 minutes) combined with active VR motivation training (60 minutes), administered 3 times per week for 4 weeks. | Device: Active tDCS<br>* Active anodal tDCS over the left DLPFC, administered for 30 minutes, three times per week for four weeks.<br>* Other names: Active Transcranial Direct Current Stimulation;Behavioral: Active VR Motivation Training<br>* Active computerized treatment with a virtual reality-based motivation training program, administered for 60 minutes, three times per week for four weeks.<br>|
| Sham Comparator: Sham tDCS + Sham VR<br>Sham tDCS over the left DLPFC (30 minutes) combined with sham VR motivation training (60 minutes), administered 3 times per week for 4 weeks. | Device: Sham tDCS<br>* Sham anodal tDCS over the left DLPFC, administered for 30 minutes, three times per week for four weeks.<br>* Other names: Sham Transcranial Direct Current Stimulation;Behavioral: Sham VR Motivation Training<br>* Sham computerized training in a virtual reality-based environment, administered for 60 minutes, three times per week for four weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Scale of Prodromal Symptoms - Negative Subscale (SOPS-Neg) |  | 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Scale of Prodromal Symptoms - Positive Subscale (SOPS-Pos) |  | 8 weeks | 
| Global Function: Role scale |  | 8 weeks | 
| Global Function: Social scale |  | 8 weeks | 
| Beck Scale for Suicidal Ideation (BSS) |  | 4 weeks | 
| Calgary Depression Scale for Schizophrenia |  | 4 weeks | 
| MATRICS Consensus Cognitive Battery (MCCB) |  | 4 weeks | 
| Relationships Across Domains (RAD) |  | 4 weeks | 
| Reading the Mind in the Eyes Task (RMET) |  | 4 weeks | 
| The Awareness of Social Inferences Test (TASIT) |  | 4 weeks | 
| Emotion Recognition - 40 (ER-40) |  | 4 weeks | 
| Interpersonal Reactivity Index (IRI) |  | 4 weeks | 
| Simulator Sickness Questionnaire (SSQ) |  | 4 weeks | 
| Functional Brain Imaging | Change in regional brain activity measured with functional MRI | 4 weeks | 
| Structural Brain Imaging | Changes in brain structure (e.g., white matter tract integrity) measure with structural MRI | 4 weeks |