Non-Invasive Brain Stimulation for Traumatic Brain Injury

(SMART Trial)

Overseen By David Darrow, MD

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: University of Minnesota

Disqualifiers: Severe TBI, Visual impairment, others

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

Compensation: Varies

Number of Visits: 6

Duration: 6 weeks

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if a gentle, non-invasive brain stimulation called TACS can enhance thinking and decision-making in individuals with mild to moderate traumatic brain injury (TBI). Participants will receive either the actual stimulation or a placebo treatment without stimulation. The trial seeks adults who have experienced a mild to moderate TBI and can comfortably use a computer for assessments. As an Early Phase 1 trial, this research focuses on understanding how TACS functions in people, offering participants the opportunity to explore this innovative treatment.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. Please consult with the trial coordinators for more details.

What prior data suggests that this non-invasive brain stimulation is safe for traumatic brain injury?

Research has shown that non-invasive brain stimulation methods, like the one being tested, hold promise for people with traumatic brain injuries (TBI). Current studies suggest these treatments are generally safe. Trials focused on TBI have found no major safety issues. In fact, results indicate that patients tolerate these techniques well. While more research is needed, existing evidence suggests this type of therapy has a good safety record. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about non-invasive brain stimulation for traumatic brain injury (TBI) because it offers a novel approach compared to traditional treatments like medication and rehabilitation therapy. Unlike standard care, which often focuses on managing symptoms, this method uses external non-invasive techniques to stimulate brain activity directly. This approach has the potential to enhance brain recovery by promoting neural connections without the need for surgery or drugs. Additionally, it could offer faster improvements in cognitive function, providing new hope for TBI patients seeking effective and accessible recovery options.

What evidence suggests that this trial's treatments could be effective for traumatic brain injury?

Research has shown that non-invasive brain stimulation, such as transcutaneous alternating current stimulation (TACS), may enhance thinking skills in individuals with traumatic brain injury (TBI). Some studies suggest these methods can slightly improve abilities like memory and decision-making for TBI patients. A review of research also highlights positive effects of these brain stimulation techniques on brain disorders, including TBI. In this trial, participants will join either a stimulation group or a sham group. Although more research is needed, early findings suggest potential benefits from this treatment. ^{1 2 4 6 7}

Who Is on the Research Team?

David Darrow, MD MPH

Principal Investigator

University of Minnesota

Are You a Good Fit for This Trial?

This trial is for adults over 18 who've had a mild to moderate traumatic brain injury (TBI) and can perform computerized tests. They must understand the consent process and commit to all appointments. It's not for those with severe TBI, scalp wounds, pacemakers/defibrillators, non-English speakers, or visual issues affecting computer use.

Inclusion Criteria

I am over 18, had a mild to moderate brain injury, can do computer tasks, and can follow the study plan.

I am over 18, can do computer tasks, and can attend all appointments.

Exclusion Criteria

Implanted defibrillator or pacemaker

Visual impairment that hinders ability to complete computerized assessments

I have an open wound on my scalp.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive transcutaneous alternating current stimulation (tACS) or sham stimulation once weekly for six weeks to improve cognitive function and decision-making after traumatic brain injury

6 weeks

6 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• COGED
• External non-invasive stimulation

Trial Overview The study is testing two types of external non-invasive brain stimulation: transcutaneous alternating current stimulation (TACS) and vagal nerve stimulation (tnVNS), aiming to improve cognitive function and decision-making after a TBI.

How Is the Trial Designed?

Group I: Stimulation Active Control 2 Interventions

Stimulation

Group II: Sham Placebo Group 1 Intervention

No stimulation

Who Is Running the Clinical Trial?

University of Minnesota

Lead Sponsor

Trials

1,459

Recruited

1,623,000+

United States Department of Defense

Collaborator

Trials

940

Recruited

339,000+

Uniformed Services University of the Health Sciences

Collaborator

Trials

130

Recruited

91,100+

Published Research Related to This Trial

Noninvasive transcranial stimulation can be used to create temporary brain dysfunctions, helping researchers understand the role of specific brain networks in various tasks.

This technique also has therapeutic potential, as it can induce lasting changes in brain function and behavior, making it a promising tool for treatment in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Consensus: Motor cortex plasticity protocols. Ziemann, U., Paulus, W., Nitsche, MA., et al.[2016]

Non-invasive brain stimulation (NIBS), particularly repetitive transcranial magnetic stimulation (rTMS), has been shown to significantly reduce depressive symptoms in traumatic brain injury (TBI) patients, based on a meta-analysis of 10 trials involving 234 participants.

While rTMS demonstrated strong short-term efficacy, the effects diminished after 1-2 months, and the safety profile was favorable with minimal adverse events reported, indicating NIBS could be a safe treatment option for depression in TBI patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of Non-Invasive Brain Stimulation for Treating Depression in Patients with Traumatic Brain Injury: A Meta-Analysis and Meta-Regression of Randomized Controlled Trials. Chang, CH., Chou, PH., Chuang, HY., et al.[2023]

Non-invasive brain stimulation (NIBS) shows potential for improving cognitive functions in individuals with traumatic brain injury (TBI), but the evidence is still limited, with only five studies meeting the criteria for analysis.

Among the studies, transcranial direct current stimulation (tDCS) demonstrated significant improvements in attention and memory in two out of three studies, while repetitive transcranial magnetic stimulation (rTMS) showed limited effectiveness, indicating a need for further research to establish reliable outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Effect of Non-Invasive Brain Stimulation (NIBS) on Executive Functioning, Attention and Memory in Rehabilitation Patients with Traumatic Brain Injury: A Systematic Review. Hara, T., Shanmugalingam, A., McIntyre, A., et al.[2021]

Noninvasive brain stimulation (NBS) techniques like transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) may help enhance neuroplasticity and recovery after traumatic brain injury (TBI) by modulating brain activity and facilitating learning.

While there is promising theoretical evidence from both animal and human studies suggesting that NBS can reduce injury effects and promote recovery, more research is needed in TBI patients to confirm these benefits and determine the best stimulation methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Noninvasive brain stimulation to modulate neuroplasticity in traumatic brain injury. Villamar, MF., Santos Portilla, A., Fregni, F., et al.[2022]

The review of 10 placebo-controlled studies on non-invasive brain stimulation (NIBS) for cognitive performance in traumatic brain injury (TBI) patients found insufficient high-quality evidence to support its effectiveness, particularly for cognitive functions other than attention.

While NIBS showed some potential benefits for depression in TBI patients, it did not consistently improve other cognitive deficits like executive function or memory, highlighting the need for further research due to the high risk of bias in the studies reviewed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Effectiveness of Non-Invasive Brain Stimulation Alone or Combined with Cognitive Training on the Cognitive Performance of Patients With Traumatic Brain Injury: Α Systematic Review. Nousia, A., Martzoukou, M., Liampas, I., et al.[2022]

Transcranial direct current stimulation (tDCS) is a safe and non-invasive treatment that shows promise in improving cognitive recovery in patients with traumatic brain injury (TBI), as evidenced by multiple studies reporting enhanced coma recovery and cognitive performance.

While tDCS can be effective on its own, combining it with other therapies like cognitive rehabilitation and physical therapy may lead to even better outcomes, and neurophysiological measures like EEG and TMS can serve as useful biomarkers for tracking progress.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial direct current stimulation (tDCS) effects on traumatic brain injury (TBI) recovery: A systematic review. Zaninotto, AL., El-Hagrassy, MM., Green, JR., et al.[2022]

Noninvasive brain stimulation (NBS) techniques, such as transcranial magnetic stimulation and transcranial direct current stimulation, show potential for both assessing and treating traumatic brain injury (TBI) by modulating brain activity and promoting recovery.

These techniques may help suppress harmful brain activity immediately after injury and enhance recovery during rehabilitation, but further safety research and clinical trials are needed to confirm their effectiveness and establish best practices for use in TBI patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Noninvasive brain stimulation in traumatic brain injury. Demirtas-Tatlidede, A., Vahabzadeh-Hagh, AM., Bernabeu, M., et al.[2022]

Targeted electromagnetic field (EMF) stimulation using a sinusoidal pattern can effectively promote recovery of neural circuits in a traumatic brain injury (TBI) model, as demonstrated in a Yucatan miniswine study.

Real-time measurements of EMF changes using advanced induction sensor technology showed that stimulation at specific frequencies and offsets can help restore EMF patterns to baseline levels, indicating potential for clinical applications in TBI treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Swine Model of Traumatic Brain Injury: Effects of Neuronally Generated Electromagnetic Fields and Electromagnetic Field Stimulation on Traumatic Brain Injury-Related Changes. Brazdzionis, J., Radwan, MM., Thankam, F., et al.[2023]

Non-invasive vagus nerve stimulation showed a greater responder rate in reducing migraine days compared to sham therapy, particularly benefiting participants with aura, although the overall reduction in monthly migraine days was not statistically significant.

The treatment demonstrated a strong safety profile, with no serious device-related adverse events reported during the study involving 336 participants, despite the trial being prematurely terminated due to the COVID-19 pandemic.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Non-invasive vagus nerve stimulation for prevention of migraine: The multicenter, randomized, double-blind, sham-controlled PREMIUM II trial. Najib, U., Smith, T., Hindiyeh, N., et al.[2022]

The study demonstrates that endovascular cortical stimulation is a safe and effective method for recording neural activity without the need for craniotomy, allowing for high-bandwidth intracranial EEG.

Electrical stimulation of neural tissue resulted in faster response times and more localized activation compared to visual stimulation, highlighting the potential of this technique for targeted therapeutic applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cortical Brain Stimulation with Endovascular Electrodes. Gerboni, G., John, SE., Ronayne, SM., et al.[2020]

Brain stimulation techniques, particularly transcranial direct current stimulation, show promise in promoting recovery from traumatic brain injury (TBI), especially in chronic phases, but evidence for acute phase efficacy and safety is still limited.

Most current brain stimulation interventions are non-targeted and lack sufficient clinical trials, highlighting the need for larger, well-designed studies to better understand their potential benefits in enhancing neuroplasticity and functional outcomes after TBI.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical utility of brain stimulation modalities following traumatic brain injury: current evidence. Li, S., Zaninotto, AL., Neville, IS., et al.[2022]

Noninvasive cortical stimulation techniques are valuable in neurorehabilitation, helping researchers understand how the brain recovers function after injury.

These techniques can modulate cortical excitability, potentially enhancing the effects of rehabilitation training and providing insights into the physiological mechanisms behind recovery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Noninvasive cortical stimulation in neurorehabilitation: a review. Harris-Love, ML., Cohen, LG.[2016]

Non-invasive brain stimulation (NBS) techniques like transcranial direct current stimulation (tDCS) and transcranial magnetic stimulation (TMS) show promise in treating traumatic brain injury (TBI) by potentially reducing symptoms and promoting neuroplasticity, based on a review of existing literature.

While animal and human studies suggest that NBS can help mitigate injury severity and enhance brain recovery, more research is needed to confirm its safety and effectiveness in TBI patients, as current evidence remains largely speculative.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

NEUROPLASTICITY AND BRAIN STIMULATION: DEVELOPING INTERVENTIONS TO PROMOTE RECOVERY FROM STROKE AND TRAUMATIC BRAIN INJURY. Malathi, H., Dhananjoy, L., Tarekar, A., et al.[2023]

Citations

1. sciencedirect.com sciencedirect.com/science/article/pii/S0006899323004043

The effects of non-invasive brain stimulation on disorder ... This systematic review and meta-analysis aimed to investigate the therapeutic effects of non-invasive brain stimulation (NIBS) techniques.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8301762/

Intervention Effect of Non-Invasive Brain Stimulation on ... The present findings suggest that NIBS is moderately effective in improving cognitive functions among people with TBI.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3342413/

NONINVASIVE BRAIN STIMULATION IN TRAUMATIC BRAIN ... This review introduces different techniques of noninvasive brain stimulation, which may find potential use in TBI.

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0278584623001495

Effectiveness of rTMS and tDCS treatment for chronic TBI ... This study aims at providing a systematic review and meta-analysis on the effectiveness of repetitive transcranial magnetic stimulation (TMS) and transcranial ...

5. frontiersin.org frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2023.1219043/full

Efficacy of non-invasive brain stimulation for disorders ... Results: A total of 17 studies with 377 DoC patients were included. NIBS significantly improved the state of consciousness in DoC patients when ...

6. withpower.com withpower.com/trial/early-phase-1-brain-injuries-traumatic-3-2022-678fb

Non-Invasive Brain Stimulation for Traumatic Brain Injury While more research is needed, current studies suggest it is generally safe, with no major safety concerns reported in trials for traumatic brain injury and ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT06228872

"Cognitive Rehabilitation With Direct Current Transcranial ... The outcomes of this clinical trial have the potential to identify an effective and accessible therapeutic approach to enhance cognitive function in individuals ...