Treating Mild Traumatic Brain Injury With High Definition Transcranial Direct Current Stimulation (HDtDCS-TBI)

• ClinicalTrials.gov Identifier: NCT04869059
• Recruitment Status: Recruiting
• First Posted: May 3, 2021
• Last Update Posted: February 11, 2022
• Sponsor: The University of Texas at Dallas
• Information provided by (Responsible Party): The University of Texas at Dallas

Study Description

Brief Summary:

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., presupplementary motor area) thought to aid in memory will improve verbal retrieval in military 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 and concussion history predict responses to treatment over time, both on assessments administered within the intervention period and at follow-up.

Condition or disease	Intervention/treatment	Phase
Traumatic Brain Injury	Device: Transcranial direct current stimulation; Device: sham tDCS	Phase 2

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 15 sessions to (2) sham tDCS following the same schedule. Additionally, after completing the initial active or sham treatment and 3-month follow-up testing sessions, selected participants will be invited back for newly assigned treatment conditions, 20 minutes over 15 sessions and will be and re-evaluated at 2- and 3-months follow-up testing sessions.

Veterans 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).

Primary outcome verbal retrieval measures and secondary neuropsychological and electroencephalography (EEG) measures will be collected after treatment sessions 5, 10, and 15 and two times following treatment competition (i.e., 2-months and 3-months). For participants selected for the second round of intervention, primary outcome verbal memory measures and secondary neuropsychological and electroencephalography (EEG) measures will be collected again after treatment sessions 5, 10, and 15 and two times following competition of the second treatment (i.e., 2-months and 3-months).

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 80 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment

Intervention 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 15 sessions to (2) sham tDCS following the same schedule.

Additionally, after completing the initial active or sham treatment and 3-month follow-up testing sessions, selected participants will be invited back for newly assigned treatment conditions, 20 minutes over 15 sessions and will be and re-evaluated at 2- and 3-months follow-up testing sessions.

• Masking: Triple (Participant, Care Provider, Outcomes Assessor)
• Masking Description: Participants, assessors, and technicians interacting with participants will be blind to assigned conditions.
• Primary Purpose: Treatment
• Official Title: Treatment of Verbal Retrieval Deficits in Mild Traumatic Brain Injury With High Definition Transcranial Direct Current Stimulation
• Actual Study Start Date: August 1, 2021
• Estimated Primary Completion Date: August 31, 2023
• Estimated Study Completion Date: August 31, 2023

Arms and Interventions

Arm	Intervention/treatment
Experimental: Transcranial direct current stimulation; 20 minutes of 1 milliamp transcranial direct current stimulation to presupplementary motor area for 15 sessions	Device: 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
Sham Comparator: Sham transcranial direct current stimulation; 20 minutes of sham transcranial direct current stimulation to presupplementary motor area for 15 sessions	Device: sham tDCS; 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.

Outcome Measures

Primary Outcome Measures :

1. Treatment group differences in change from Baseline to 3-months Post-Treatment on the Controlled Oral Word Association Test [ Time Frame: Outcome measures will be assessed as change over a period of 17 weeks: Change from baseline to 3-month Post-Treatment ]

   Evaluation of treatment group differences in change on the Control Word Association Test from baseline to 3-months. Metric: Number of Correct Items Generated

   Benton, L.A., Hamsher, K., & Sivan, A.B., (1994). Multilingual aphasia examination. Iowa City: AJA Associates.

2. Treatment group differences in change from Baseline to 2-months Post-Treatment on the Controlled Oral Word Association Test [ Time Frame: Outcome measures will be assessed as change over a period of 13 weeks: Change from baseline to 2-month Post-Treatment ]

   Evaluation of treatment group differences in change on the Control Word Association Test from baseline to 2-months. Metric: Number of Correct Items Generated

   Benton, L.A., Hamsher, K., & Sivan, A.B., (1994). Multilingual aphasia examination. Iowa City: AJA Associates.

3. Treatment group differences in change from Baseline to 3-months Post-Treatment in Category Fluency [ Time Frame: Outcome measures will be assessed as change over a period of 17 weeks: Change from baseline to 3-month Post-Treatment ]

   Evaluation of treatment group differences in change in Category Fluency from baseline to 3-months. Metric: Number of Correct Items Generated

   Benton, L.A., Hamsher, K., & Sivan, A.B., (1994). Multilingual aphasia examination. Iowa City: AJA Associates.

4. Treatment group differences in change from Baseline to 2-months Post-Treatment in Category Fluency [ Time Frame: Outcome measures will be assessed as change over a period of 13 weeks: Change from baseline to 2-month Post-Treatment ]

   Evaluation of treatment group differences in change in Category Fluency from baseline to 2-months. Metric: Number of Correct Items Generated

   Benton, L.A., Hamsher, K., & Sivan, A.B., (1994). Multilingual aphasia examination. Iowa City: AJA Associates.

5. Treatment group differences in change from Baseline to 3-months Post-Treatment on the Semantic Object Retrieval Test [ Time Frame: Outcome measures will be assessed as change over a period of 17 weeks: Change from baseline to 3-month Post-Treatment ]

   Evaluation of treatment group differences in change in Semantic Object Retrieval Test from baseline to 3-months. Metric: Number of Correct Retrievals

   Kaplan, E., Goodglass, H., & Weintraub, S., (1983). Boston Naming Test (2nd ed.). Lea & Febiger: Philadelphia.

6. Treatment group differences in change from Baseline to 2-months Post-Treatment on the Semantic Object Retrieval Test [ Time Frame: Outcome measures will be assessed as change over a period of 13 weeks: Change from baseline to 2-month Post-Treatment ]

   Evaluation of treatment group differences in change in Semantic Object Retrieval Test from baseline to 2-months. Metric: Number of Correct Retrievals

   Kaplan, E., Goodglass, H., & Weintraub, S., (1983). Boston Naming Test (2nd ed.). Lea & Febiger: Philadelphia.

7. Treatment group differences in change from Baseline to 3-months Post-Treatment on the Boston Naming Test [ Time Frame: Outcome measures will be assessed as change over a period of 17 weeks: Change from baseline to 3-month Post-Treatment ]

   Evaluation of treatment group differences in change in Boston Naming Test from baseline to 3-months. Metric: Number of Correct Names Retrieved

   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.

8. Treatment group differences in change from Baseline to 2-months Post-Treatment on the Boston Naming Test [ Time Frame: Outcome measures will be assessed as change over a period of 13 weeks: Change from baseline to 2-month Post-Treatment ]

   Evaluation of treatment group differences in change in Boston Naming Test from baseline to 2-months. Metric: Number of Correct Names Retrieved

   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.

9. Treatment group differences in change from Baseline to 3-months Post-Treatment on California Verbal Learning Test [ Time Frame: Outcome measures will be assessed as change over a period of 17 weeks: Change from baseline to 3-month Post-Treatment ]

   Evaluation of treatment group differences in change in California Verbal Learning Test from baseline to 3-months. Metric: Number of Correct Retrievals

   Delis DC, Kramer JH, Kaplan E, Ober BA. (2017). California verbal learning test (3rd Ed.). Pearson Publishing: San Antonio, TX.

10. Treatment group differences in change from Baseline to 2-months Post-Treatment on California Verbal Learning Test [ Time Frame: Outcome measures will be assessed as change over a period of 13 weeks: Change from baseline to 2-month Post-Treatment ]

    Evaluation of treatment group differences in change in California Verbal Learning Test from baseline to 2-months. Metric: Number of Correct Retrievals

    Delis DC, Kramer JH, Kaplan E, Ober BA. (2017). California verbal learning test (3rd Ed.). Pearson Publishing: San Antonio, TX.

Secondary Outcome Measures :

1. Treatment group differences in change from Baseline to 3-months Post-Treatment on the Trail Making Test (Part A) [ Time Frame: Outcome measures will be assessed as change over a period of 17 weeks: Change from baseline to 3-month Post-Treatment ]

   Evaluation of treatment group differences in change on the Trail Making Test (Part A) from baseline to 3-months. 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.

2. Treatment group differences in change from Baseline to 2-months Post-Treatment on the Trail Making Test (Part A) [ Time Frame: Outcome measures will be assessed as change over a period of 13 weeks: Change from baseline to 2-month Post-Treatment ]

   Evaluation of treatment group differences in change on the Trail Making Test (Part A) from baseline to 2-months. 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.

3. Treatment group differences in change from Baseline to 3-months Post-Treatment on the Trail Making Test (Part B) [ Time Frame: Outcome measures will be assessed as change over a period of 17 weeks: Change from baseline to 3-month Post-Treatment ]

   Evaluation of treatment group differences in change on the Trail Making Test (Part B) from baseline to 3-months. 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.

4. Treatment group differences in change from Baseline to 2-months Post-Treatment on the Trail Making Test (Part B) [ Time Frame: Outcome measures will be assessed as change over a period of 13 weeks: Change from baseline to 2-month Post-Treatment ]

   Evaluation of treatment group differences in change on the Trail Making Test (Part B) from baseline to 2-months. 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.

5. Treatment group differences in change from Baseline to 3-months Post-Treatment on the Delis Kaplan Color Word Interference Test [ Time Frame: Outcome measures will be assessed as change over a period of 17 weeks: Change from baseline to 3-month Post-Treatment ]

   Evaluation of treatment group differences in change on the Delis Kaplan Color Word Interference Test from baseline to 3-months. 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.

6. Treatment group differences in change from Baseline to 2-months Post-Treatment on the Delis Kaplan Color Word Interference Test [ Time Frame: Outcome measures will be assessed as change over a period of 13 weeks: Change from baseline to 2-month Post-Treatment ]

   Evaluation of treatment group differences in change on the Trail Making Test (Part B) from baseline to 2-months. Metric: Time to Name Items

   Reitan, R.M., (1958). Validity of the Trail Making Test as an indicator of organic brain damage. Percept. Motor Skill., 8, 271-276.

7. Treatment group differences in change from Baseline to 3-months Post-Treatment on the Digit Span Forward [ Time Frame: Outcome measures will be assessed as change over a period of 17 weeks: Change from baseline to 3-month Post-Treatment ]

   Evaluation of treatment group differences in change in Digit Span Forward from baseline to 3-months. Metric: Memory Span

   Wechsler, D., (2008). Wechsler adult intelligence scale-Fourth Edition (WAIS-IV). San Antonio, TX: NCS Pearson.

8. Treatment group differences in change from Baseline to 2-months Post-Treatment on the Digit Span Forward [ Time Frame: Outcome measures will be assessed as change over a period of 13 weeks: Change from baseline to 2-month Post-Treatment ]

   Evaluation of treatment group differences in change in Digit Span Forward from baseline to 2-months. Metric: Memory Span

   Wechsler, D., (2008). Wechsler adult intelligence scale-Fourth Edition (WAIS-IV). San Antonio, TX: NCS Pearson.

9. Treatment group differences in change from Baseline to 3-months Post-Treatment on the Digit Span Backward [ Time Frame: Outcome measures will be assessed as change over a period of 17 weeks: Change from baseline to 3-month Post-Treatment ]

   Evaluation of treatment group differences in change in Digit Span Backward from baseline to 3-months. Metric: Memory Span

   Wechsler, D., (2008). Wechsler adult intelligence scale-Fourth Edition (WAIS-IV). San Antonio, TX: NCS Pearson.

10. Treatment group differences in change from Baseline to 2-months Post-Treatment on the Digit Span Backward [ Time Frame: Outcome measures will be assessed as change over a period of 13 weeks: Change from baseline to 2-month Post-Treatment ]

    Evaluation of treatment group differences in change in Digit Span Backward from baseline to 2-months. Metric: Memory Span

    Wechsler, D., (2008). Wechsler adult intelligence scale-Fourth Edition (WAIS-IV). San Antonio, TX: NCS Pearson.

11. Treatment group differences in change from Baseline to 3-months Post-Treatment on the Rey-Osterrieth Complex Figure Test [ Time Frame: Outcome measures will be assessed as change over a period of 17 weeks: Change from baseline to 3-month Post-Treatment ]

    Evaluation of treatment group differences in change in Rey-Osterrieth Complex Figure Test scores from baseline to 3-months. 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.

12. Treatment group differences in change from Baseline to 2-months Post-Treatment on the Rey-Osterrieth Complex Figure Test [ Time Frame: Outcome measures will be assessed as change over a period of 13 weeks: Change from baseline to 2-month Post-Treatment ]

    Evaluation of treatment group differences in change in Rey-Osterrieth Complex Figure Test scores from baseline to 2-months. 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.

13. Treatment group differences in change from Baseline to 3-months Post-Treatment on the Digit Symbol Substitution Test [ Time Frame: Outcome measures will be assessed as change over a period of 17 weeks: Change from baseline to 3-month Post-Treatment ]

    Evaluation of treatment group differences in change on the Digit Symbol Substitution Test from baseline to 3-months. Metric: Number of Items

    Wechsler, D., (2008). Wechsler adult intelligence scale-Fourth Edition (WAIS-IV). San Antonio, TX: NCS Pearson.

14. Treatment group differences in change from Baseline to 2-months Post-Treatment on the Digit Symbol Substitution Test [ Time Frame: Outcome measures will be assessed as change over a period of 13 weeks: Change from baseline to 2-month Post-Treatment ]

    Evaluation of treatment group differences in change on the Digit Symbol Substitution Test from baseline to 2-months. Metric: Number of Items

    Wechsler, D., (2008). Wechsler adult intelligence scale-Fourth Edition (WAIS-IV). San Antonio, TX: NCS Pearson.

15. Treatment group differences in change from Baseline to 3-months Post-Treatment on the Grooved Pegboard Test [ Time Frame: Outcome measures will be assessed as change over a period of 17 weeks: Change from baseline to 3-month Post-Treatment ]

    Evaluation of treatment group differences in change on the Grooved Pegboard Test from baseline to 3-months. Metric: Completion Time

    Matthews, C.G., and Klove, H. (1964). Instruction manual for the adult neuropsychology test. Madison. Wis: University of Wisconsin Medical School.

16. Treatment group differences in change from Baseline to 2-months Post-Treatment on the Grooved Pegboard Test [ Time Frame: Outcome measures will be assessed as change over a period of 13 weeks: Change from baseline to 2-month Post-Treatment ]

    Evaluation of treatment group differences in change on the Grooved Pegboard Test from baseline to 2-months. Metric: Completion Time

    Matthews, C.G., and Klove, H. (1964). Instruction manual for the adult neuropsychology test. Madison. Wis: University of Wisconsin Medical School.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria: Participants are to be between the ages of 18-75, have previously served in the US armed services, and have had a traumatic brain injury that has led to 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: Exclusion criteria include a history of a psychological or neurological disorder, including, dementia of any type, epilepsy or other seizure disorders, severe traumatic brain injury, 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. Additionally, exclusion criteria include inability to give informed consent; cranial implants or skull defects that affect tDCS administration; and use of medications that interact with or potentially interact with tDCS effects, including, anti-convulsants, amphetamines, L-dopa, carbamazepine, sulpiride, pergolide, lorazepam, rivastigmine, dextromethorphan, D-cycloserine, flunarizine, ropinirole, or citalopram.

Contacts and Locations

Contacts

Contact: Tyler Rawlinson, BS; 972-883-3180; tyler.rawlinson@utdallas.edu

Contact: Jill Ritter, BS; 972-883-4853; jill.ritter@utdallas.edu

Locations

United States, Texas

The University of Texas at Dallas; Recruiting

Dallas, Texas, United States, 75235

Contact: Tyler Rawlinson, BS 972-883-3180 tyler.rawlinson@utdallas.edu

Contact: Kelsey Watson, MA 972-883-3171 kelsey.watson@utdallas.edu

Sub-Investigator: Michael Motes, PhD

Sub-Investigator: Gail Tillman, PhD

Sponsors and Collaborators

The University of Texas at Dallas

Investigators

• Principal Investigator: John Hart, MD; University of Texas at Dallas

More Information

• Responsible Party: The University of Texas at Dallas
• ClinicalTrials.gov Identifier: NCT04869059
• Other Study ID Numbers: UTD-TDCSTBI-21-15; CDMRP-PT190081 ( Other Identifier: CDMRP ); W81XWH-20-1-0846 ( Other Grant/Funding Number: DOD-CDMRP-USAMRDC )
• First Posted: May 3, 2021
• Last Update Posted: February 11, 2022
• Last Verified: April 2021

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes
• Product Manufactured in and Exported from the U.S.: No

Keywords provided by The University of Texas at Dallas:

Traumatic brain injury; transcranial direct current stimulation; electroencephalography; cognition; veteran traumatic brain injury

Additional relevant MeSH terms:

Brain Injuries; Brain Injuries, Traumatic; Brain Concussion; Wounds and Injuries; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Head Injuries, Closed; Wounds, Nonpenetrating