Transcranial Direct Current Stimulation for Mild Traumatic Brain Injury

(HDtDCS-TBI Trial)

Overseen By Ashna Adhikari

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: The University of Texas at Dallas

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

Disqualifiers: Dementia, Epilepsy, Severe TBI, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 34

Duration: 5 weeks

136 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether a gentle electrical treatment, known as transcranial Direct Current Stimulation (tDCS), can improve memory in military veterans with mild traumatic brain injuries. The trial focuses on enhancing word recall and other cognitive skills, with some participants receiving the actual treatment and others a placebo. Veterans experiencing difficulty remembering words after a mild to moderate brain injury may be suitable candidates for this study. As an unphased trial, it provides veterans the opportunity to contribute to research that could advance memory treatments for brain injuries.

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 prior data suggests that transcranial direct current stimulation is safe for improving verbal retrieval in military veterans with traumatic brain injuries?

Research has shown that transcranial direct current stimulation (tDCS) is generally safe for people. One study found tDCS to be safe for patients with severe brain injuries, indicating it is well-tolerated even in serious cases.

Additionally, tDCS has been tested for other conditions and is considered non-invasive, as it doesn't involve surgery or entering the body. Most people experience only mild side effects, such as tingling or a slight itch on the skin where the device is placed. The studies mentioned have reported no serious problems related to its use.

Overall, evidence suggests that tDCS is safe for clinical use, particularly in studies focusing on brain injury. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Transcranial direct current stimulation (tDCS) is unique because it offers a non-invasive approach to treating mild traumatic brain injury (mTBI). Unlike standard care options such as cognitive therapy or medication, tDCS uses a small electrical current to stimulate specific areas of the brain, potentially enhancing neuroplasticity and improving cognitive function. Researchers are excited about tDCS because it could provide a quicker and more direct way to aid brain recovery with fewer side effects than traditional treatments. Additionally, the sham comparator in the trial helps ensure that any observed effects are truly due to the stimulation itself, providing a robust evaluation of its effectiveness.

What evidence suggests that transcranial direct current stimulation is effective for improving verbal retrieval in mild traumatic brain injury?

Research shows that transcranial direct current stimulation (tDCS), which participants in this trial may receive, can improve thinking and memory in people with brain conditions. Studies have found that tDCS boosts memory and thinking skills in those with traumatic brain injuries. This treatment helps the brain change and adapt, a process known as neuroplasticity. Although only a few small studies have focused on traumatic brain injury, early results are promising for improving thinking skills. tDCS uses gentle electric currents to enhance memory and other mental abilities. Participants in this trial may also receive sham tDCS, serving as a comparator to evaluate the effectiveness of the active treatment. ^{1 3 4 6 7}

Who Is on the Research Team?

John Hart, MD

Principal Investigator

University of Texas at Dallas

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

Interventions

• sham tDCS
• Transcranial direct current stimulation

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.

How Is the Trial Designed?

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 United States, European Union, Canada for the following indications:

Approved in United States as tDCS for:

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

Approved in European Union as tDCS for:

• Major depressive disorder
• Chronic pain
• Stroke rehabilitation
• Traumatic brain injury rehabilitation

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+

Published Research Related to This Trial

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]

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]

Microdermabrasion significantly reduced skin resistance by about 32%, allowing for higher doses of transcranial direct current stimulation (tDCS) without increasing skin sensations or device limitations.

The study found that while microdermabrasion increased perceived sensations slightly when not combined with sonication, overall, it enabled safer and more effective delivery of tDCS by lowering the voltage needed to achieve the same current.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Microdermabrasion facilitates direct current stimulation by lowering skin resistance. Chhatbar, PY., Liu, S., Ramakrishnan, V., 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]

High Definition transcranial direct current stimulation (HD-tDCS) is safe and well-tolerated in older adults, with no serious adverse events reported during a study involving 101 participants at stimulation intensities of 2 mA and 3 mA.

The study demonstrated effective blinding, as participants could not accurately distinguish between active and sham stimulation, indicating that HD-tDCS can be reliably used in clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tolerability and blinding of 4x1 high-definition transcranial direct current stimulation (HD-tDCS) at two and three milliamps. Reckow, J., Rahman-Filipiak, A., Garcia, S., et al.[2020]

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]

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]

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) appears to be safe and well-tolerated in youth, based on a synthesis of studies involving 156 children and a total of 864 active sessions.

The reviewed literature supports the acceptability of tDCS in pediatric populations, with only a small percentage of sessions (4.4%) conducted on neurotypical controls, indicating a focus on clinical subjects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systematic Review on the Safety and Tolerability of Transcranial Direct Current Stimulation in Children and Adolescents. Buchanan, DM., Bogdanowicz, T., Khanna, N., et al.[2021]

Citations

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Transcranial direct current stimulation (tDCS) effects on ... Multiple studies showed improved coma recovery scales in disorders of consciousness, and improved cognition on neuropsychological assessments.

2. apps.dtic.mil apps.dtic.mil/sti/pdfs/AD1172218.pdf

High-Definition Transcranial Direct Current Stimulation (HD ... The purpose of this research is to use high-definition transcranial direct current stimulation (HD-. tDCS) to treat neurosensory postconcussive ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1388245722008690

High-definition transcranial direct current stimulation ... High Definition transcranial Direct Current Stimulation (HD-tDCS) has been shown to improve cognitive performance in individuals with chronic traumatic brain ...

4. frontiersin.org frontiersin.org/journals/neuroergonomics/articles/10.3389/fnrgo.2023.1170473/full

A map of evidence using transcranial direct current ... Only two small TBI trials have been conducted based on the most recent systematic review of tDCS effectiveness for cognition following neurological impairment.

5. clinicaltrials.gov clinicaltrials.gov/study/NCT06228872

"Cognitive Rehabilitation With Direct Current Transcranial ... Transcranial Direct Current Stimulation (tDCS) has shown effectiveness in enhancing neuroplasticity in various neurological and psychiatric conditions 63.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8235194/

Transcranial Direct Current Stimulation as a Treatment Tool ... Mild traumatic brain injury (mTBI) has been defined as a transient (<24 h) condition of confusion and/or loss of consciousness for less than ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S2666459324000088

The safety and feasibility of transcranial direct current ... Our phase I safety study indicated that a single course of tDCS was safe in patients with severe traumatic brain injury.