Treating Civilian Traumatic Brain Injury With High Definition Transcranial Direct Current Stimulation (ciTBI-HDtDCS)

Study Overview
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Brief Summary
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The purpose of the study is to test whether low level electric stimulation, called transcranial Direct Current Stimulation (tDCS), on the part of the brain (i.e., pre-supplementary motor area) thought to aid in memory will improve verbal retrieval in civilian (non-military, non-veteran) participants with histories of traumatic brain injuries. The primary outcome measures are neuropsychological assessments of verbal retrieval, and the secondary measures are neuropsychological assessments of other cognitive abilities and electroencephalography (EEG) measures. Additionally, the study will examine the degree to which baseline assessments of cognition, concussion history, structural brain imaging, and EEG predict responses to treatment over time, both on assessments administered within the intervention period and at follow-up.

Detailed Description
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Using two treatment arms, the study will examine improvement of verbal retrieval and other cognitive deficits associated with remote traumatic brain injury by comparing (1) 1 milliamp transcranial direct current stimulation (tDCS) active treatment applied to presupplementary motor area for 20 minutes over 10 sessions to (2) sham tDCS following the same schedule. Additionally, after completing the initial active or sham treatment and 2-month follow-up testing sessions, participants will be invited back for newly assigned treatment conditions, 20 minutes over 10 sessions and will be re-evaluated at 2-months follow-up testing sessions. Civilians with histories of traumatic brain injuries and observed cognitive deficits will be randomly assigned to one of the two treatment arms (and re-assigned for the second round of intervention, as described above). Primary outcome verbal retrieval measures, secondary neuropsychological and electroencephalography (EEG) measures, and prescreening assessments for study concussion history and contraindications for treatment will be collected prior to being assigned to a treatment arm (i.e., baseline). Magnetic resonance imaging of the brain will be obtained only at the baseline assessment. Primary outcome verbal retrieval measures and secondary neuropsychological and electroencephalography (EEG) measures will be collected after treatment session 10 and one time following treatment competition (i.e., 2-months). For participants who complete the second round of intervention, primary outcome verbal memory measures and secondary neuropsychological and electroencephalography (EEG) measures will be collected again after treatment session 10 and one time following competition of the second treatment (i.e., 2-months).

Official Title
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Treatment of Word Finding Difficulties and Verbal Retrieval Deficits in Civilians Who Sustain a Chronic Traumatic Brain Injury With High Definition Transcranial Direct Current Stimulation

Conditions
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Traumatic Brain Injury, Word Finding Difficulty, Acquired Brain Injury, Cognitive Change

Intervention / Treatment
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* Device: Active Transcranial direct current stimulation
* Device: Sham Transcranial direct current stimulation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants are to be between the ages of 18-85, are non-military personnel and not veterans, and have had a traumatic brain injury (more than a year ago prior to study participation) that has led to a complaint of word finding difficulty since the brain injury, confirmed to represent a verbal retrieval deficit based on neuropsychological testing criteria. Traumatic brain injury must be in the mild to moderate range based on evaluation, including the Ohio State TBI Identification Method (administered by our research group). You must be fluent in speaking and reading English. Exclusion Criteria: an implanted/electronic device, such as a pacemaker, metallic cranial or intracranial implant (e.g., ventriculoperitoneal shunt), or a neurostimulator (e.g., vagus nerve stimulator, spinal stimulator, deep brain stimulator, etc.). skull defects a history of a psychological or neurological disorder, including, dementia of any type, epilepsy or other seizure disorders, post-traumatic stress disorder, brain tumor, present drug abuse, stroke, blood vessel abnormalities in the brain, Parkinson's disease, Huntington's disease, or multiple sclerosis. inability to give informed consent currently pregnant not a native English speaker

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 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: Crossover Assignment
Interventional Model Description: Participants will be randomly assigned to 1 of 2 treatment arms: (1) 1 milliamp transcranial direct current stimulation (tDCS) active treatment applied to presupplementary motor area for 20 minutes over 10 sessions to (2) sham tDCS following the same schedule. Additionally, after completing the initial active or sham treatment and 2-month follow-up testing sessions, all participants will be invited back for newly assigned treatment conditions, 20 minutes over 10 sessions and will be and re-evaluated at 2-months follow-up testing sessions.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Active to Sham Transcranial direct current stimulation<br>Subjects in this arm will first be randomly assigned to receive active stimulation. After completion of active stimulation, subjects will be assigned to sham stimulation. | Device: Active Transcranial direct current stimulation<br>* Transcranial direct current stimulation will be delivered via a Neuroelectrics Starstim tES. Stimulation will consist of 1 milliamp stimulation, with anodal stimulation delivered at electrode Fz (International 10/10 System for electroencephalography electrode placement) and electrodes F7, FP1, FP2, and F8 as returns. All electrodes are 1 cm diameter Ag/AgCl electrodes and make contact with the scalp via connective gel. Stimulation will linearly ramp up from 0 milliamps to 1 milliamp over 60 seconds, then remain at 1 milliamp of stimulation over 20 minutes, and finally ramping down at to 0 milliamps over 60 seconds.<br>* Other names: High definition transcranial direct current stimulator, Neuroelectrics Starstim tES, SN E20200930-10;Device: Sham Transcranial direct current stimulation<br>* Sham transcranial direct current stimulation will be delivered via a Neuroelectrics Starstim tES. The sham setup will consist of anodal electrode Fz (International 10/10 System for electroencephalography electrode placement) and electrodes F7, FP1, FP2, and F8 as returns. All electrodes are 1 cm diameter Ag/AgCl electrodes and make contact with the scalp via connective gel. Stimulation will linearly ramp up from 0 milliamps to 1 milliamp over 60 seconds, ramp down to 0 milliamps over 60 seconds and then be left off for 20 minutes.<br>|
| Experimental: Sham to Active transcranial direct current stimulation<br>Subjects in this arm will first be randomly assigned to receive sham stimulation. After completion of sham stimulation, subjects will be assigned to active stimulation. | Device: Active Transcranial direct current stimulation<br>* Transcranial direct current stimulation will be delivered via a Neuroelectrics Starstim tES. Stimulation will consist of 1 milliamp stimulation, with anodal stimulation delivered at electrode Fz (International 10/10 System for electroencephalography electrode placement) and electrodes F7, FP1, FP2, and F8 as returns. All electrodes are 1 cm diameter Ag/AgCl electrodes and make contact with the scalp via connective gel. Stimulation will linearly ramp up from 0 milliamps to 1 milliamp over 60 seconds, then remain at 1 milliamp of stimulation over 20 minutes, and finally ramping down at to 0 milliamps over 60 seconds.<br>* Other names: High definition transcranial direct current stimulator, Neuroelectrics Starstim tES, SN E20200930-10;Device: Sham Transcranial direct current stimulation<br>* Sham transcranial direct current stimulation will be delivered via a Neuroelectrics Starstim tES. The sham setup will consist of anodal electrode Fz (International 10/10 System for electroencephalography electrode placement) and electrodes F7, FP1, FP2, and F8 as returns. All electrodes are 1 cm diameter Ag/AgCl electrodes and make contact with the scalp via connective gel. Stimulation will linearly ramp up from 0 milliamps to 1 milliamp over 60 seconds, ramp down to 0 milliamps over 60 seconds and then be left off for 20 minutes.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Controlled Oral Word Association Test | Evaluation of treatment differences (active versus sham) in change on the Control Word Association Test. Metric: Number of Correct Items Generated Benton, L.A., Hamsher, K., & Sivan, A.B., (1994). Multilingual aphasia examination. Iowa City: AJA Associates. | Treatment differences (active versus sham) in change from Baseline to immediately and 2-months Post-Treatment. | 
| Category Fluency | Evaluation of treatment differences (active versus sham) in change on Category Fluency. Metric: Number of Correct Items Generated Benton, L.A., Hamsher, K., & Sivan, A.B., (1994). Multilingual aphasia examination. Iowa City: AJA Associates. | Treatment differences (active versus sham) in change from Baseline to immediately and 2-months Post-Treatment. | 
| The Boston Naming Test | Evaluation of treatment differences (active versus sham) in change on The Boston Naming Test. Metric: Number of Correct Items Generated. Kaplan, E., Goodglass, H., & Weintraub, S., (1983). Boston Naming Test (2nd ed.). Lea & Febiger: Philadelphia. | Treatment differences (active versus sham) in change from Baseline to immediately and 2-months Post-Treatment. | 
| Semantic Object Retrieval Test | Evaluation of treatment differences (active versus sham) in change in Semantic Object Retrieval Test. Metric: Number of Correct Retrievals. Kraut, M.A., Cherry, B., Pitcock, C.B., Anand, R., Li, J. Vestal, L., Henderson, V.W., and Hart, J. Jr. (2007). The Semantic Object Retrieval Test (SORT) in amnestic cognitive impairment. Cogn. Behav. Neurol. 20, 62- 67. | Treatment differences (active versus sham) in change from Baseline to immediately and 2-months Post-Treatment. | 
| The Delis Kaplan Color Word Interference Test | Evaluation of treatment differences (active versus sham) in change on the Delis Kaplan Color Word Interference Test. Metric: Time to Name Items Delis, D.C., Kaplan, E., & Kramer, J.H., (2001). Delis-Kaplan Executive Function System. San Antonio, TX: The Psychological Corporation. | Treatment differences (active versus sham) in change from Baseline to immediately and 2-months Post-Treatment. | 
| California Verbal Learning Test | Evaluation of treatment differences (active versus sham) in change in California Verbal Learning Test. Metric: Number of Total learning items and Correct Recalls. Delis DC, Kramer JH, Kaplan E, Ober BA. (2017). California verbal learning test (3rd Ed.). Pearson Publishing: San Antonio, TX. | Treatment differences (active versus sham) in change from Baseline to immediately and 2-months Post-Treatment. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Trail Making Test (Parts A & B) | Evaluation of treatment differences (active versus sham) in change on the Trail Making Test (Parts A&B). Metric: Time to Solution Reitan, R.M., (1958). Validity of the Trail Making Test as an indicator of organic brain damage. Percept. Motor Skill., 8, 271-276. | Treatment differences (active versus sham) in change from Baseline to immediately and 2-months Post-Treatment. | 
| Digit Span Forward & Backward | Evaluation of treatment differences (active versus sham) in change in Digit Span Forward & Backward. Metric: Memory Span Wechsler, D., (2008). Wechsler adult intelligence scale-Fourth Edition (WAIS-IV). San Antonio, TX: NCS Pearson. | Treatment differences (active versus sham) in change from Baseline to immediately and 2-months Post-Treatment. | 
| Rey-Osterrieth Complex Figure Test | Evaluation of treatment differences (active versus sham) in change in Rey-Osterrieth Complex Figure Test scores. Metric: Score Rey, A. (1941). L'examen psychologique dans les cas d'encéphalopathie traumatique. (Les problems.). [The psychological examination in cases of traumatic encepholopathy. Problems.]. Archives de Psychologie, 28, 215- 285. | Treatment differences (active versus sham) in change from Baseline to immediately and 2-months Post-Treatment. | 
| The Digit Symbol Substitution Test | Evaluation of treatment differences (active versus sham) in change on the Digit Symbol Substitution Test. Metric: Number of Items Wechsler, D., (2008). Wechsler adult intelligence scale-Fourth Edition (WAIS-IV). San Antonio, TX: NCS Pearson. | Treatment differences (active versus sham) in change from Baseline to immediately and 2-months Post-Treatment. | 
| Task-based electroencephalography (EEG) markers during a Go-NoGo task | Evaluation of treatment differences (active versus sham) in EEG change on a Go-NoGo task with different levels of perceptual/semantic complexity. Metric: event-related potentials and time frequency changes. Mudar RA, Chiang HS, Eroh J, et al. The Effects of Amnestic Mild Cognitive Impairment on Go/NoGo Semantic Categorization Task Performance and Event-Related Potentials. J Alzheimers Dis. 2016;50(2):577-590. | Treatment differences (active versus sham) in change from Baseline to immediately and 2-months Post-Treatment. | 
| Task-based electroencephalography (EEG) markers during a Semantic Object Memory Retrieval task | Evaluation of treatment differences (active versus sham) in EEG change on a Semantic Object Retrieval task. Metric: event-related potentials and time frequency changes. Chiang HS, Mudar RA, Spence JS, et al. Age-related changes in feature-based object memory retrieval as measured by event-related potentials. Biol Psychol. 2014;100:106-114. | Treatment differences (active versus sham) in change from Baseline to immediately and 2-months Post-Treatment. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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transcranial direct current stimulation, electroencephalography, Cognition