Transcranial Direct Current Stimulation for Mild Traumatic Brain Injury

(HDtDCS-TBI Trial)

Overseen by John Hart, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: The University of Texas at Dallas

Must not be taking: Anticonvulsants, Amphetamines, Dopaminergics, others

Disqualifiers: Dementia, Epilepsy, Severe TBI, others

No Placebo Group

Approved in 3 Jurisdictions

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

You may need to stop taking certain medications that could interact with the study treatment. These include anti-convulsants, amphetamines, and several others like L-dopa and citalopram. It's important to discuss your current medications with the study team to see if any changes are needed.

What data supports the effectiveness of this treatment for mild traumatic brain injury?

Research shows that high-definition transcranial direct current stimulation (HD-tDCS) can improve cognitive performance in people with chronic traumatic brain injury, suggesting potential benefits for those with mild traumatic brain injury as well. ^{1 2 3 4 5}

Is transcranial direct current stimulation (tDCS) safe for humans?

Transcranial direct current stimulation (tDCS) is generally considered safe for humans, with no reports of serious adverse effects or irreversible injury in over 33,200 sessions across various populations, including potentially vulnerable groups. However, there is limited evidence on its safety in children and adolescents, and some reports suggest it could cause skin irritation or injury. ^{6 7 8 9 10}

How is transcranial direct current stimulation (tDCS) different from other treatments for mild traumatic brain injury?

Transcranial direct current stimulation (tDCS) is unique because it uses a non-invasive method to modulate brain activity through small electrical currents applied via electrodes on the scalp, which can be more precisely targeted with high-definition tDCS (HD-tDCS) compared to conventional methods. This approach is different from other treatments that may not offer such targeted neural modulation. ^{1 2 3 5 11}

Research Team

John Hart, MD

Principal Investigator

University of Texas at Dallas

Eligibility Criteria

This trial is for US military veterans aged 18-75 with mild to moderate traumatic brain injury that has affected their verbal skills. They must be fluent in English and have no severe neurological disorders, drug abuse history, or conditions affecting the brain's blood vessels. Participants taking certain medications or with cranial implants cannot join.

Inclusion Criteria

Participants must have previously served in the US armed services

I have difficulty finding words due to a brain injury.

Participants must be fluent in speaking and reading English

Exclusion Criteria

Inability to give informed consent

I have implants or defects in my skull that could interfere with brain stimulation treatments.

I am not taking any medication that could affect tDCS treatment.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 20 minutes of 1 milliamp transcranial direct current stimulation or sham treatment to presupplementary motor area for 15 sessions

5 weeks

15 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment with assessments at 2-months and 3-months post-treatment

3 months

2 visits (in-person)

Second Round of Treatment (Optional)

Selected participants receive a second round of treatment with 20 minutes of tDCS or sham for 15 sessions, followed by follow-up assessments

5 weeks

15 visits (in-person)

Second Follow-up

Participants are monitored for safety and effectiveness after the second round of treatment with assessments at 2-months and 3-months post-second treatment

3 months

2 visits (in-person)

Treatment Details

Interventions

• sham tDCS (Behavioural Intervention)
• Transcranial direct current stimulation (Behavioural Intervention)

Trial Overview The study tests if a low-level electric brain stimulation technique called transcranial Direct Current Stimulation (tDCS) can improve memory-related verbal skills in participants with traumatic brain injuries. It compares real tDCS to sham (fake) treatment using neuropsychological assessments and EEG measures.

Participant Groups

Group I: Transcranial direct current stimulation Experimental Treatment 1 Intervention

20 minutes of 1 milliamp transcranial direct current stimulation to presupplementary motor area for 15 sessions

Group II: Sham transcranial direct current stimulation Placebo Group 1 Intervention

20 minutes of sham transcranial direct current stimulation to presupplementary motor area for 15 sessions

Transcranial direct current stimulation is already approved in Canada for the following indications:

Approved in Canada as tDCS for:

• Depression
• Chronic pain
• Stroke rehabilitation
• Traumatic brain injury rehabilitation

Who Is Running the Clinical Trial?

The University of Texas at Dallas

Lead Sponsor

Trials

71

Recruited

108,000+

Dr. Richard Benson

The University of Texas at Dallas

Chief Executive Officer since 2016

PhD in Molecular and Cell Biology from the University of Texas at Dallas

Dr. Patrizia Cavazzoni

The University of Texas at Dallas

Chief Medical Officer

MD from Harvard Medical School

Findings from Research

High-Definition transcranial Direct Current Stimulation (HD-tDCS) at amplitudes up to 4 mA was well tolerated by 292 older adults, with no safety-related adverse events reported and mostly mild sensations experienced during sessions.

The study demonstrated effective blinding for both participants and researchers, indicating that the sham stimulation was convincing, which supports the use of higher amplitudes for potentially greater therapeutic effects in older adults.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tolerability and blinding of high-definition transcranial direct current stimulation among older adults at intensities of up to 4 mA per electrode. El Jamal, C., Harrie, A., Rahman-Filipiak, A., et al.[2023]

Optimized high-definition montages for transcranial direct current stimulation (tDCS) can increase stimulation intensity by an average of 0.3 V/m compared to unoptimized montages, which is crucial for targeting areas beneath skull defects.

Large skull defects with titanium or acrylic plates can reduce stimulation intensity by about 80%, while smaller defects filled with cerebrospinal fluid or scar tissue can increase stimulation intensity by about 200%, highlighting the importance of individual anatomical considerations in tDCS treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimized high-definition tDCS in patients with skull defects and skull plates. Guillen, A., Truong, DQ., Datta, A., et al.[2023]

In a study involving veterans with chronic traumatic brain injury (TBI), active high-definition transcranial direct current stimulation (HD-tDCS) significantly improved cognitive performance, as evidenced by increased theta activity in the brain during a Go-NoGo task, compared to a sham treatment.

The results suggest that HD-tDCS induces specific changes in brain oscillatory activity, which could help identify individuals who are more likely to benefit from this type of intervention in the future.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-definition transcranial direct current stimulation modulates theta response during a Go-NoGo task in traumatic brain injury. Chiang, HS., Motes, M., Kraut, M., et al.[2023]

In a study involving 20 patients with posttraumatic encephalopathy, high-definition transcranial direct current stimulation (HD-tDCS) significantly improved cerebral blood flow (CBF) and cerebral blood volume (CBV), indicating enhanced oxygen delivery to brain tissue.

The treatment also reduced areas of hypoperfusion and ischemia, suggesting that HD-tDCS may be an effective non-pharmacologic intervention for improving cerebral perfusion after traumatic brain injury.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cerebral Hemodynamics After Transcranial Direct Current Stimulation (tDCS) in Patients with Consequences of Traumatic Brain Injury. Trofimov, AO., Kalentiev, G., Karelsky, M., et al.[2020]

The novel high-definition transcranial direct current stimulation (HD-tDCS) setup was found to be safe and well-tolerated, with fewer adverse effects compared to conventional tDCS, based on a study involving 60 healthy participants.

HD-tDCS significantly improved cognitive performance on a visual task, indicating its potential for more effective neural modulation, while also being compatible with simultaneous fMRI without causing significant heating or image quality issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, Tolerability, Blinding Efficacy and Behavioural Effects of a Novel MRI-Compatible, High-Definition tDCS Set-Up. Gbadeyan, O., Steinhauser, M., McMahon, K., et al.[2022]

Transcranial Direct Current Stimulation (tDCS) has been shown to be safe, with no reports of Serious Adverse Effects or irreversible injuries across over 33,200 sessions involving more than 1,000 subjects, including vulnerable populations.

Safety assessments indicate that the current densities used in conventional tDCS (≤4 milliamperes) are significantly lower than those that could potentially cause brain injury, suggesting that tDCS protocols are well within safe limits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of Transcranial Direct Current Stimulation: Evidence Based Update 2016. Bikson, M., Grossman, P., Thomas, C., et al.[2022]

Transcranial Direct Current Stimulation (tDCS) is generally considered safe, but there are concerns that it could lead to significant negative effects in healthy individuals.

The scientific community needs to be alerted about the potential risks of tDCS, emphasizing the importance of protecting healthy volunteers from possible harm.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of transcranial direct current stimulation in healthy participants. Boccard-Binet, S., Sen, A.[2021]

High-Definition transcranial Direct Current Stimulation (HD-tDCS) is a safe and well-tolerated method for non-invasive brain stimulation, even when using a 2 mA current for 22 minutes.

Using a 6% benzocaine topical numbing agent significantly reduces discomfort during HD-tDCS sessions, which can improve the quality of sham-controlled studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reduced discomfort during high-definition transcutaneous stimulation using 6% benzocaine. Guleyupoglu, B., Febles, N., Minhas, P., et al.[2021]

References

1. United States pubmed.ncbi.nlm.nih.gov

Tolerability and blinding of high-definition transcranial direct current stimulation among older adults at intensities of up to 4 mA per electrode. [2023]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Optimized high-definition tDCS in patients with skull defects and skull plates. [2023]

3. Netherlands pubmed.ncbi.nlm.nih.gov

High-definition transcranial direct current stimulation modulates theta response during a Go-NoGo task in traumatic brain injury. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Cerebral Hemodynamics After Transcranial Direct Current Stimulation (tDCS) in Patients with Consequences of Traumatic Brain Injury. [2020]

5. United States pubmed.ncbi.nlm.nih.gov

Safety, Tolerability, Blinding Efficacy and Behavioural Effects of a Novel MRI-Compatible, High-Definition tDCS Set-Up. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Safety of Transcranial Direct Current Stimulation: Evidence Based Update 2016. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Safety of transcranial direct current stimulation in healthy participants. [2021]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Systematic Review on the Safety and Tolerability of Transcranial Direct Current Stimulation in Children and Adolescents. [2021]

9. United States pubmed.ncbi.nlm.nih.gov

Tolerability and blinding of 4x1 high-definition transcranial direct current stimulation (HD-tDCS) at two and three milliamps. [2020]

10. England pubmed.ncbi.nlm.nih.gov

Microdermabrasion facilitates direct current stimulation by lowering skin resistance. [2023]

11. Switzerland pubmed.ncbi.nlm.nih.gov

Reduced discomfort during high-definition transcutaneous stimulation using 6% benzocaine. [2021]