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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Cognitive Change; Traumatic Brain Injury; Acquired Brain Injury; Word Finding Difficulty
• Intervention / Treatment: Device: Active Transcranial direct current stimulation; Device: Sham Transcranial direct current stimulation

Detailed Description

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).

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Hsueh-Sheng Chiang, MD, PhD; Phone Number: 469-708-4925; Email: hschiang@utdallas.edu
• Study Contact Backup: Name: Jill Ritter, BS; Phone Number: 469-708-4925; Email: jill.ritter@utdallas.edu

Study Locations

• United States
  • Texas
    • Dallas, Texas, United States, 75390
      • Recruiting
      • University of Texas Southwestern Medical Center
      • Contact: Hsueh-Sheng Chiang, MD PhD; Phone Number: 469-708-4925; Email: hschiang@utdallas.edu
    • Dallas, Texas, United States, 75235
      • Recruiting
      • The University of Texas at Dallas
      • Contact: Jill Ritter, BS; Phone Number: 469-708-4925; Email: jill.ritter@utdallas.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Active to Sham Transcranial direct current stimulation; 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; 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.; Other Names: tDCS; 1 milliamp tDCS; High definition tDCS; High definition transcranial direct current stimulator, Neuroelectrics Starstim tES, SN E20200930-10; Device: Sham Transcranial direct current stimulation; 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.
Experimental: Sham to Active transcranial direct current stimulation; 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; 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.; Other Names: tDCS; 1 milliamp tDCS; High definition tDCS; High definition transcranial direct current stimulator, Neuroelectrics Starstim tES, SN E20200930-10; Device: Sham Transcranial direct current stimulation; 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.

What is the study measuring?

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	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	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.	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.	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	Treatment differences (active versus sham) in change from Baseline to immediately and 2-months Post-Treatment.
Rey Auditory Verbal Learning Test and alternative lists	Evaluation of treatment differences (active versus sham) in change in Rey Auditory Verbal Learning Test. Metric: Number of Total learning items and Correct Recalls.	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	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	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	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	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.	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.	Treatment differences (active versus sham) in change from Baseline to immediately and 2-months Post-Treatment.

Collaborators and Investigators

• Sponsor: The University of Texas at Dallas
• Collaborators: National Institute on Deafness and Other Communication Disorders (NIDCD)
• Investigators: Principal Investigator: John Hart, MD, University of Texas at Dallas

Publications and helpful links

General Publications

• Benton, L.A., Hamsher, K., & Sivan, A.B., (1994). Multilingual aphasia examination. Iowa City: AJA Associates.
• Kaplan, E., Goodglass, H., & Weintraub, S., (1983). Boston Naming Test (2nd ed.). Lea & Febiger: Philadelphia.
• Kraut MA, Cherry B, Pitcock JA, Anand R, Li J, Vestal L, Henderson VW, Hart J Jr. The Semantic Object Retrieval Test (SORT) in amnestic mild cognitive impairment. Cogn Behav Neurol. 2007 Mar;20(1):62-7. doi: 10.1097/WNN.0b013e3180335f7d.
• Delis, D.C., Kaplan, E., & Kramer, J.H., (2001). Delis-Kaplan Executive Function System. San Antonio, TX: The Psychological Corporation.
• Schmidt M. Rey Auditory and Verbal Learning Test: A Handbook. Los Angeles: Western Psychological Services; 1996.
• Reitan, R.M., (1958). Validity of the Trail Making Test as an indicator of organic brain damage. Percept. Motor Skill., 8, 271-276.
• Wechsler, D., (2008). Wechsler adult intelligence scale-Fourth Edition (WAIS-IV). San Antonio, TX: NCS Pearson.
• 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.
• Mudar RA, Chiang HS, Eroh J, Nguyen LT, Maguire MJ, Spence JS, Kung F, Kraut MA, Hart J. The Effects of Amnestic Mild Cognitive Impairment on Go/NoGo Semantic Categorization Task Performance and Event-Related Potentials. J Alzheimers Dis. 2016;50(2):577-90. doi: 10.3233/JAD-150586.
• Chiang HS, Mudar RA, Spence JS, Pudhiyidath A, Eroh J, DeLaRosa B, Kraut MA, Hart J Jr. Age-related changes in feature-based object memory retrieval as measured by event-related potentials. Biol Psychol. 2014 Jul;100:106-14. doi: 10.1016/j.biopsycho.2014.05.010. Epub 2014 Jun 6.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2023
• Primary Completion (Estimated): December 1, 2024
• Study Completion (Estimated): December 1, 2024

Study Registration Dates

• First Submitted: June 2, 2022
• First Submitted That Met QC Criteria: June 2, 2022
• First Posted (Actual): June 7, 2022

Study Record Updates

• Last Update Posted (Actual): April 26, 2024
• Last Update Submitted That Met QC Criteria: April 24, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: transcranial direct current stimulation; Cognition; electroencephalography
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Craniocerebral Trauma; Trauma, Nervous System; Language Disorders; Communication Disorders; Speech Disorders; Brain Injuries; Wounds and Injuries; Brain Injuries, Traumatic; Aphasia; Anomia
• Other Study ID Numbers: STU-2022-0999; 1K99DC020185-01 (U.S. NIH Grant/Contract); 5K99DC020185-02 (U.S. NIH Grant/Contract)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes