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| Name | Class |
|---|---|
| National Institute of Mental Health (NIMH) | NIH |
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Cognitive impairments in schizophrenia are the most debilitating aspect of the illness and poorly treated by current medications. This study investigates transcranial direct current stimulation (tDCS) - a safe, noninvasive weak electrical current delivery to stimulate brain function - as a novel therapeutic for cognition in schizophrenia. Integrating neurostimulation, electrophysiology and neuroimaging, this project aims to study tDCS effects on cognition by verifying therapeutic target engagement, evaluating the tolerability of tDCS sessions, and optimizing treatment parameters.
Cognitive deficits are a strong predictor of functional outcome in schizophrenia, yet poorly remediated by current treatments. Disturbances in dorsolateral prefrontal cortex (DLPFC) function underlie core impairments such as in cognitive control and thus represent a critical target for novel therapeutics. Initial studies indicate transcranial direct-current stimulation (tDCS) may be effective in reducing symptoms due to DLPFC dysfunction. While tDCS potentially represents an exciting, novel therapeutic advance, a number of basic questions should be addressed prior to conducting larger-scale clinical trials, including: verifying therapeutic target engagement, optimizing treatment parameters, and evaluating for meaningful clinical effects. Recent studies employing tDCS to enhance prefrontal cortical function in schizophrenia applied stimulating electrodes over the left frontal scalp region, putatively targeting the left DLPFC. However, explicit confirmation of such target engagement is lacking. Further, EEG studies have demonstrated close links of frontal cortical gamma oscillations to cognitive control processes but modulation of this critical physiologic process has not been investigated. Accordingly, the primary aim of this study is to employ multimodal imaging to explicitly test for the assumed DLPFC engagement (fMRI) and modulation of frontal gamma activity (EEG) by tDCS. This study will also investigate the optimization of tDCS application parameters. Analogous to dose-finding investigations in drug studies, we will conduct a parametric investigation of optimal current strengths. Also, while there is extensive evidence for tolerability of single session tDCS, confirmation of feasibility of multisession optimized protocols in schizophrenia is lacking and so will be explicitly evaluated.
In summary, a successful outcome of this study would provide tDCS the sound mechanistic and methodologic basis for more definitive testing in large-scale clinical trials as a highly innovative therapeutic intervention for cognitive impairments in schizophrenia.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 2.5mA | Experimental | Active stimulation group will receive 20 minutes of 2.5 mA transcranial direct current stimulation. |
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| 2.0mA | Experimental | Active stimulation group will receive 20 minutes of 2.0 mA transcranial direct current stimulation. |
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| 1.5mA | Experimental | Active stimulation group will receive 20 minutes of 1.5 mA transcranial direct current stimulation. |
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| 0mA | Sham Comparator | This will be an active sham involving transcranial direct current stimulation, though stimulation will be brief (15 msec) and have low current (0.11 mA) pulses every 550 ms. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| transcranial direct current stimulation | Device | transcranial direct current stimulation (tDCS) is a safe, noninvasive, weak electrical current delivery that stimulates brain function. It is a novel therapeutic for cognition in schizophrenia. |
| Measure | Description | Time Frame |
|---|---|---|
| tDCS Engagement of DLPFC Activity Indexed by fMRI BOLD Imaging | Change from Baseline to week 1 as measured by modulation of fMRI BOLD signal in DLPFC in the context of cognitive control task performance. | 1 week |
| tDCS Engagement of DLPFC Activity Indexed by Modulation of Frontal Cortical Gamma Oscillations | Change from Baseline to week 1 as measured by EEG frontal gamma oscillations in the context of cognitive control task performance | 1 week |
| Measure | Description | Time Frame |
|---|---|---|
| Optimal tDCS Strength for DLPFC Engagement | Change from baseline to 1 week in DLPFC engagement across conditions (1.5 vs 2.0 vs 2.5 mA) | 1 Week |
| Tolerability and Feasibility of Multi-session tDCS in Schizophrenia |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Raymond Cho, M.D., M.Sc. | Baylor College of Medicine | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Baylor College of Medicine | Houston | Texas | 77030 | United States |
Data will be open to sharing after primary findings of study have been published
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The primary reasons for ineligibility were not meeting the early psychosis criterion (< 5 years of treatment), not taking any medication, and drug use. There were also many who did not even enter screening due to the assessment that they would highly likely not meet the threshold of requirement cognitive impairment (MATRICS score 40).
The reason we have fewer subjects randomized than enrolled is that some participants did not meet criteria to be randomized. These subjects were consented and completed many assessments, but were ultimately not randomized due to how they scored on some assessments. For instance, some peoples MCCB score was too high to be randomized into the study.
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| ID | Title | Description |
|---|---|---|
| FG000 | 2.5mA | Active stimulation group will receive 20 minutes of 2.5 mA transcranial direct current stimulation. transcranial direct current stimulation: transcranial direct current stimulation (tDCS) is a safe, noninvasive, weak electrical current delivery that stimulates brain function. It is a novel therapeutic for cognition in schizophrenia. |
| FG001 | 2.0mA | Active stimulation group will receive 20 minutes of 2.0 mA transcranial direct current stimulation. transcranial direct current stimulation: transcranial direct current stimulation (tDCS) is a safe, noninvasive, weak electrical current delivery that stimulates brain function. It is a novel therapeutic for cognition in schizophrenia. |
| FG002 | 1.5mA | Active stimulation group will receive 20 minutes of 1.5 mA transcranial direct current stimulation. transcranial direct current stimulation: transcranial direct current stimulation (tDCS) is a safe, noninvasive, weak electrical current delivery that stimulates brain function. It is a novel therapeutic for cognition in schizophrenia. |
| FG003 | 0mA (Active Placebo) | This will be an active sham involving transcranial direct current stimulation, though stimulation will be brief (15 msec) and have low current (0.11 mA) pulses every 550 ms. transcranial direct current stimulation: transcranial direct current stimulation (tDCS) is a safe, noninvasive, weak electrical current delivery that stimulates brain function. It is a novel therapeutic for cognition in schizophrenia. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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| ID | Title | Description |
|---|---|---|
| BG000 | 2.5mA | Active stimulation group will receive 20 minutes of 2.5 mA transcranial direct current stimulation. transcranial direct current stimulation: transcranial direct current stimulation (tDCS) is a safe, noninvasive, weak electrical current delivery that stimulates brain function. It is a novel therapeutic for cognition in schizophrenia. |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | tDCS Engagement of DLPFC Activity Indexed by fMRI BOLD Imaging | Change from Baseline to week 1 as measured by modulation of fMRI BOLD signal in DLPFC in the context of cognitive control task performance. | Our analytic strategy involved defining regions of interest (ROI) derived from group averages across all study subjects but due to unforeseen circumstances, we recruited far too few subjects to derive meaningful group averages. Individual subject and by extension, condition-specific averages that are based on such ROIs, could therefore not be derived. However, we will upload our raw data to the National Data Archive to be accessed for any potential analyses with data pooled from other studies. | Posted | 1 week |
|
Two Weeks
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 2.5mA | Active stimulation group will receive 20 minutes of 2.5 mA transcranial direct current stimulation. transcranial direct current stimulation: transcranial direct current stimulation (tDCS) is a safe, noninvasive, weak electrical current delivery that stimulates brain function. It is a novel therapeutic for cognition in schizophrenia. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Exacerbation of Psychotic Symptoms | Psychiatric disorders | Non-systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Minor Burn | Skin and subcutaneous tissue disorders | Non-systematic Assessment | Minor burn at location of tDCS electrode placement. |
Despite concerted and exhaustive subject recruitment efforts, the total number of patients completing the protocol was minimal. As such the sample size was inadequate for deriving any meaningful descriptive statistics or statistical comparisons.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Raymond Cho | Baylor College of Medicine | 713-798-7781 | Raymond.Cho@bcm.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Apr 12, 2019 | Jun 27, 2020 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D012559 | Schizophrenia |
| D011618 | Psychotic Disorders |
| ID | Term |
|---|---|
| D019967 | Schizophrenia Spectrum and Other Psychotic Disorders |
| D001523 | Mental Disorders |
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| ID | Term |
|---|---|
| D065908 | Transcranial Direct Current Stimulation |
| ID | Term |
|---|---|
| D004599 | Electric Stimulation Therapy |
| D013812 | Therapeutics |
| D003295 | Convulsive Therapy |
| D013000 | Psychiatric Somatic Therapies |
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The percentage of participants able to complete the full study.
| 1 week |
| BG001 |
| 2.0mA |
Active stimulation group will receive 20 minutes of 2.0 mA transcranial direct current stimulation. transcranial direct current stimulation: transcranial direct current stimulation (tDCS) is a safe, noninvasive, weak electrical current delivery that stimulates brain function. It is a novel therapeutic for cognition in schizophrenia. |
| BG002 | 1.5mA | Active stimulation group will receive 20 minutes of 1.5 mA transcranial direct current stimulation. transcranial direct current stimulation: transcranial direct current stimulation (tDCS) is a safe, noninvasive, weak electrical current delivery that stimulates brain function. It is a novel therapeutic for cognition in schizophrenia. |
| BG003 | 0mA (Active Placebo) | This will be an active sham involving transcranial direct current stimulation, though stimulation will be brief (15 msec) and have low current (0.11 mA) pulses every 550 ms. transcranial direct current stimulation: transcranial direct current stimulation (tDCS) is a safe, noninvasive, weak electrical current delivery that stimulates brain function. It is a novel therapeutic for cognition in schizophrenia. |
| BG004 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| MCCB Score | Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB). Intended to provide a relatively brief evaluation of key cognitive domains that are relevant to schizophrenia and related disorders, the battery is appropriate for use as an outcome measure for clinical trials of cognition-enhancing drugs, when studying cognitive remediation, to measure cognitive change, and as a cognitive reference point for nonintervention studies of schizophrenia and other severe psychiatric disorders. Higher scores are better. | Mean | Standard Deviation | units on a scale |
|
| OG001 | 2.0mA | Active stimulation group will receive 20 minutes of 2.0 mA transcranial direct current stimulation. transcranial direct current stimulation: transcranial direct current stimulation (tDCS) is a safe, noninvasive, weak electrical current delivery that stimulates brain function. It is a novel therapeutic for cognition in schizophrenia. |
| OG002 | 1.5mA | Active stimulation group will receive 20 minutes of 1.5 mA transcranial direct current stimulation. transcranial direct current stimulation: transcranial direct current stimulation (tDCS) is a safe, noninvasive, weak electrical current delivery that stimulates brain function. It is a novel therapeutic for cognition in schizophrenia. |
| OG003 | 0mA (Active Placebo) | This will be an active sham involving transcranial direct current stimulation, though stimulation will be brief (15 msec) and have low current (0.11 mA) pulses every 550 ms. transcranial direct current stimulation: transcranial direct current stimulation (tDCS) is a safe, noninvasive, weak electrical current delivery that stimulates brain function. It is a novel therapeutic for cognition in schizophrenia. |
|
| Primary | tDCS Engagement of DLPFC Activity Indexed by Modulation of Frontal Cortical Gamma Oscillations | Change from Baseline to week 1 as measured by EEG frontal gamma oscillations in the context of cognitive control task performance | Our analytic strategy involved defining regions of interest (ROI) derived from group averages across all study subjects but due to unforeseen circumstances, we recruited far too few subjects to derive meaningful group averages. Individual subject and by extension, condition-specific averages that are based on such ROIs, could therefore not be derived. However, we will upload our raw data to the National Data Archive to be accessed for any potential analyses with data pooled from other studies. | Posted | 1 week |
|
|
| Secondary | Optimal tDCS Strength for DLPFC Engagement | Change from baseline to 1 week in DLPFC engagement across conditions (1.5 vs 2.0 vs 2.5 mA) | Our analytic strategy involved defining regions of interest (ROI) derived from group averages across all study subjects but due to unforeseen circumstances, we recruited far too few subjects to derive meaningful group averages. Individual subject and by extension, condition-specific averages that are based on such ROIs, could therefore not be derived. However, we will upload our raw data to the National Data Archive to be accessed for any potential analyses with data pooled from other studies. | Posted | 1 Week |
|
|
| Secondary | Tolerability and Feasibility of Multi-session tDCS in Schizophrenia | The percentage of participants able to complete the full study. | Due to unforeseen circumstances, we were unable to sufficiently recruit enough subjects to complete the originals plans for analysis. The percentages below are the percent of subjects who completed each condition. | Posted | Number | percentage of participants completed | 1 week |
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| 0 |
| 1 |
| 0 |
| 1 |
| 0 |
| 1 |
| EG001 | 2.0mA | Active stimulation group will receive 20 minutes of 2.0 mA transcranial direct current stimulation. transcranial direct current stimulation: transcranial direct current stimulation (tDCS) is a safe, noninvasive, weak electrical current delivery that stimulates brain function. It is a novel therapeutic for cognition in schizophrenia. | 0 | 2 | 1 | 2 | 1 | 2 |
| EG002 | 1.5mA | Active stimulation group will receive 20 minutes of 1.5 mA transcranial direct current stimulation. transcranial direct current stimulation: transcranial direct current stimulation (tDCS) is a safe, noninvasive, weak electrical current delivery that stimulates brain function. It is a novel therapeutic for cognition in schizophrenia. | 0 | 1 | 0 | 1 | 0 | 1 |
| EG003 | 0mA (Active Placebo) | This will be an active sham involving transcranial direct current stimulation, though stimulation will be brief (15 msec) and have low current (0.11 mA) pulses every 550 ms. transcranial direct current stimulation: transcranial direct current stimulation (tDCS) is a safe, noninvasive, weak electrical current delivery that stimulates brain function. It is a novel therapeutic for cognition in schizophrenia. | 0 | 4 | 0 | 4 | 0 | 4 |
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| D004191 | Behavioral Disciplines and Activities |
| D004597 | Electroshock |
| D011580 | Psychological Techniques |