Study Results
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Basic Information
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WITHDRAWN
NA
INTERVENTIONAL
2021-05-01
2023-12-31
Brief Summary
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Detailed Description
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Cognitive remediation (CR) is a psychological intervention based on principles of learning and neuroplasticity to improve neurocognitive abilities with the ultimate goal of improving community functioning. The neuroplastic effects of CR are well established with evidence for increased gray matter volume in the hippocampus and amygdala, increased activation of the medial prefrontal cortex, and increased amplitude of the mismatch negativity event-related potential following CR. In two recent randomized controlled trials (RCTs), we also demonstrated that CR improves synchronization of neural networks in the alpha and theta frequency bands. Meta-analyses support moderate transfer of these neurophysiological improvements to neurocognitive abilities (d = 0.45) and community functioning (d = 0.37). In a recent systematic review, we reported that CR approaches vary widely, but approaches that incorporate training of executive functions are generally the most effective. Based on these findings we developed a novel CR intervention specifically targeting executive functions and conducted two double-blind RCTs, in which targeted executive function training (ET) produced greater improvements in neurophysiology, neurocognition, functional skills and real-world community functioning compared to other leading forms of CR. This intervention is approximately half the duration of other CR programs, yet produces larger effect size improvements in community functioning.
Further augmentation of CR is needed to increase effect size and impact on community functioning in schizophrenia. One such augmentation strategy is via interventions that are known to enhance neuroplasticity, which is the underlying mechanism of learning. A promising neuroplasticity enhancing methodology is via non-invasive brain stimulation.
Transcranial direct current stimulation (tDCs) is the most common form of non-invasive transcranial electric stimulation (tES). Unlike other forms of transcranial electric stimulation (for example electroconvulsive therapy of ECT), tDCS is designed to modify cortical excitability by making underlying neurons more or less likely to fire but is not designed to induce depolarization or action potential in the neurons. tDCS involves application of a weak, constant (i.e., "direct") electric current from one electrode (anode) placed on the scalp to another (cathode) in order to modify cortical excitability. The application strength can be measured by amplitude of the current applied (usually one or two Amperes) and duration of application (usually around 20-30 minutes). tDCS is thought to be relatively safe with main side effect of local skin irritation and local skin burn. The risk of inducing a seizure is extremely low (mainly pediatric case report evidence), and in fact tDCS has literature support suggesting potentially anti-seizure effects. tDCS has been investigated for several therapeutic applications including cognitive disorders with promising results. There are some preliminary studies that support the feasibility, safety and promising efficacy of tDCS in combination with CR in schizophrenia. These studies are generally small and focused on cognitive domains such as working memory. More studies are needed to evaluate the added value of tDCS on effect size and impact on executive and community functioning.
Although cognitive remediation approaches such as ET improve community functioning for people with schizophrenia-spectrum disorders, these approaches may be further refined to improve efficacy. One option is to combine ET with neurostimulation designed to prime the brain for enhanced learning. In order to further increase the efficiency and effectiveness of ET it is necessary to determine whether receiving tDCS prior to engaging in this cognitive training intervention may enhance one's ability to engage in cognitive activities, or may improve their cognitive abilities. This will provide important information regarding whether the outcomes of ET can be further enhanced, which will directly inform clinical methods and optimize the effectiveness of this treatment.
The primary goal of this study is to:
(1) Examine the efficacy of combined Executive Training and tDCS compared to Executive Training combined with sham tDCS on neurocognition and functioning.
The participants for this study will be recruited from Ontario Shores inpatient units, specifically Complex General Psychiatry (CGP) inpatient units, which historically averages a length of stay of 51 to 159 days depending on the specific unit and typically comprises 70 to 75 patients at any given time with diagnoses of schizophrenia/schizophrenia spectrum disorders. Inpatients who are not expected to be discharged for 4 weeks (period needed for study interventions) will be enrolled. However, if a participant is discharged before the end of the treatment, arrangements will be made for him/her to complete the intervention by coming on-site daily for tDCS and ET.
Participants will be randomized using an online random number table to receive actual tDCS prior to engaging in ET or sham tDCS prior to engaging in ET. All participants will receive ET. The randomization sequence will be pre-generated by the study coordinator who will then inform the treating clinician. Three assessments will be completed over the course of the study: one within 1 to 2 weeks of the start of the intervention, one within 1 to 2 weeks after the intervention is complete, and one 3-months after the intervention is complete. Each assessment will last about 2.5 hours and can be conducted over two days according to participant preference. These assessments will involve paper/pencil tests and questionnaires, computerized tests, and Electroencephalogram (EEG) recordings.
Primary and secondary outcomes will be examined using Linear Mixed Models on the Intent-to-Treat sample with missing data interpolated using maximum likelihood estimation. The primary endpoint is the 3-month follow-up assessment, and secondary endpoint of post-intervention will also be examined.
Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
SINGLE
Study Groups
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Actual tDCs + ET
All interventions will involve 4 weeks of group intervention consisting of two 1-hour group sessions per week and additional practice between sessions. Half of study participants will be randomized to receive 30 minutes of transcranial direct current stimulation (tDCS) prior to beginning each ET session. ET session will begin immediately after tDCS.
Transcranial direct current stimulation
Participants will receive bilateral prefrontal anodal stimulation with cathode placed on the back of the upper neck. Transcranial direct current stimulation (tDCS) will be delivered by a research assistant under the supervision of a psychiatrist.
Executive function training
The Executive Training (ET) aspect of the study will be completed by all participants. ET sessions consist of 50% of the session practicing computerized cognitive training exercises, and 50% of the session developing cognitive strategies to use in the computerized exercises. Participants are encouraged to complete 40 minutes of computerized training per day, and complete strategy worksheets, on the unit or in the library at Ontario Shores between sessions. ET will be delivered virtually and group sessions will be conducted using the online platform Zoom. For any group sessions, a PHIPA and PIPEDA compliant license will be used. This means that participants will not be able to record their screen using Zoom or a third-party program. Dr. Best will also go through some rules during the first group Zoom session regarding the use of third-party equipment and the importance of confidentiality.
Sham tDCs + ET
All interventions will involve 4 weeks of group intervention consisting of two 1-hour group sessions per week and additional practice between sessions. Half of study participants will be randomized to receive 30 minutes of sham transcranial direct current stimulation (tDCS) prior to beginning each ET session. ET session will begin immediately after tDCS. During the sham tDCS, the procedures will be exactly the same as the real tDCS (e.g., application of electrodes), however, no stimulation will be provided when the device turned on.
Executive function training
The Executive Training (ET) aspect of the study will be completed by all participants. ET sessions consist of 50% of the session practicing computerized cognitive training exercises, and 50% of the session developing cognitive strategies to use in the computerized exercises. Participants are encouraged to complete 40 minutes of computerized training per day, and complete strategy worksheets, on the unit or in the library at Ontario Shores between sessions. ET will be delivered virtually and group sessions will be conducted using the online platform Zoom. For any group sessions, a PHIPA and PIPEDA compliant license will be used. This means that participants will not be able to record their screen using Zoom or a third-party program. Dr. Best will also go through some rules during the first group Zoom session regarding the use of third-party equipment and the importance of confidentiality.
Interventions
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Transcranial direct current stimulation
Participants will receive bilateral prefrontal anodal stimulation with cathode placed on the back of the upper neck. Transcranial direct current stimulation (tDCS) will be delivered by a research assistant under the supervision of a psychiatrist.
Executive function training
The Executive Training (ET) aspect of the study will be completed by all participants. ET sessions consist of 50% of the session practicing computerized cognitive training exercises, and 50% of the session developing cognitive strategies to use in the computerized exercises. Participants are encouraged to complete 40 minutes of computerized training per day, and complete strategy worksheets, on the unit or in the library at Ontario Shores between sessions. ET will be delivered virtually and group sessions will be conducted using the online platform Zoom. For any group sessions, a PHIPA and PIPEDA compliant license will be used. This means that participants will not be able to record their screen using Zoom or a third-party program. Dr. Best will also go through some rules during the first group Zoom session regarding the use of third-party equipment and the importance of confidentiality.
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* 18-65 years of age
* know how to use a computer
* are not abusing drugs or alcohol (criteria met for abuse in the last month)
* can read and speak English
Exclusion Criteria
* anyone with a neurological disease or neurological damage, medical illnesses that can change neurocognitive function, medical history of head injury with loss of consciousness
* with a neurological disease or neurological damage, medical illnesses that can change neurocognitive function, medical history of head injury with loss of consciousness
* those with a seizure disorder
* those who are pregnant
* those with psychotic symptoms that in the opinion of the study psychiatrist, would impose risk of distress and/or decompensation of psychosis (e.g. delusion of influence through electricity)
18 Years
65 Years
ALL
No
Sponsors
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Ontario Shores Centre for Mental Health Sciences
OTHER
University of Toronto
OTHER
Responsible Party
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Michael Best
Assistant Professor
Principal Investigators
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Michael W Best, PhD
Role: PRINCIPAL_INVESTIGATOR
University of Toronto
Locations
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Ontario Shores Centre for Mental Health Sciences (Ontario Shores)
Whitby, Ontario, Canada
Countries
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References
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Other Identifiers
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41543
Identifier Type: -
Identifier Source: org_study_id
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