tDCS for Post-Stroke Motor Impairment

Recruiting at 1 trial location

Overseen By Sanjiv Jain, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Carle Foundation Hospital

Disqualifiers: Cognitive dysfunction, Pacemaker, Pregnant, others

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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

Duration: 8 weeks

30 Participants Needed

Trial Summary

What is the purpose of this trial?

Significant motor impairments occur in 80% of individuals after moderate to severe stroke and impact the body side to the lesioned hemisphere. Typical motor impairments involve loss of dexterity with highly prevalent upper limb flexion synergy. Advances in treating flexion synergy impairments have been hampered by a lack of precision rehabilitation. Previous studies suggest and support the role of cortico-reticulospinal tract (CRST) hyperexcitability in post-stroke flexion synergy. CRST hyperexcitability is often caused by damage to the corticospinal tract (CST). We hypothesize that: 1) inhibiting the contralesional dorsal premotor cortex (cPMd) will directly reduce the CRST hyperexcitability and thus, reduce the expression of the flexion synergy; 2) facilitating the ipsilesional primary motor cortex (iM1) will improve the excitability of the damaged CST, therefore reducing the CRST hyperexcitability and the flexion synergy. we propose to use a novel targeted high-definition tDCS (THD-tDCS) to specifically modulate the targeted cortical regions for testing his hypothesis, via the following aims: Aim 1. Evaluate the effect of cathodal THD-tDCS over the cPMd on reducing the CRST hyperexcitability and the expression of flexion synergy. Aim 2. Evaluate the effect of anodal THD-tDCS over the iM1 on improving the excitability of the CST, and determine whether this, thus, also reduces the CRST hyperexcitability and the flexion synergy. Aim 3. Evaluate the confluence effect of bilateral THD-tDCS, i.e., simultaneous cathodal stimulation over the cPMd and anodal over the iM1.

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 data supports the effectiveness of this treatment for post-stroke motor impairment?

Research suggests that transcranial direct current stimulation (tDCS) can help improve motor recovery in stroke patients by changing brain activity. While some studies show mixed results, tDCS has shown promise in enhancing motor performance and learning in both healthy individuals and those recovering from a stroke. ^{1 2 3 4 5}

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

Transcranial direct current stimulation (tDCS) is generally considered safe and well-tolerated in humans, with no reports of serious adverse effects or irreversible injury in over 33,200 sessions across various populations, including potentially vulnerable groups like the elderly and those with mood disorders or stroke. ^{6 7 8 9 10}

How is the treatment tDCS for post-stroke motor impairment different from other treatments?

tDCS (Transcranial Direct Current Stimulation) is unique because it is a non-invasive brain stimulation technique that can modulate brain activity to potentially improve motor recovery after a stroke. The high-definition version (HD-tDCS) increases the precision and intensity of the stimulation, which may enhance treatment outcomes compared to standard tDCS or other rehabilitation therapies. ^{1 2 3 4 11}

Eligibility Criteria

This trial is for stroke survivors with significant motor impairments in one arm, who can consent to treatment. It's not suitable for those with abnormal muscle tone, severe limb wasting or sensory deficits, cognitive issues preventing understanding of the study, serious medical conditions, pacemaker users, metal implants in the head, known adverse reactions to TMS/tDCS or if pregnant.

Inclusion Criteria

I understand the details of the clinical trial and can consent to participate.

I have significant weakness in one arm.

Exclusion Criteria

Pregnant

I have muscle and movement issues in my limb that was not paralyzed.

My affected arm is very weak or has severe muscle loss.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo four different stimulation visits: anodal, cathodal, bilateral, and sham, with a 2-week washout period between each visit.

8 weeks

4 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Transcranial direct current stimulation (high- definition)

Trial Overview The trial tests targeted high-definition transcranial direct current stimulation (THD-tDCS) on reducing upper limb flexion synergy after a stroke. It will inhibit and facilitate specific brain regions to see if this improves motor function by modulating nerve tract excitability.

Participant Groups

Group I: Bilateral Stimulation Active Control 1 Intervention

Anodal stimulation targets the primary motor cortex (arm area) in the lesioned hemisphere and cathodal stimulation targets the dorsal premotor cortex (arm area) in the contralesional hemisphere at the same time.

Group II: Anodal stimulation Active Control 1 Intervention

Anodal stimulation targets the primary motor cortex (arm area) in the lesioned hemisphere, sham on the contralesional hemisphere.

Group III: Cathodal stimulation Active Control 1 Intervention

Cathodal stimulation targets the dorsal premotor cortex (arm area) in the contralesional hemisphere, sham on the lesioned hemisphere.

Group IV: Sham stimulation Placebo Group 1 Intervention

Sham stimulation to both hemisphere of the brain

Transcranial direct current stimulation (high- definition) is already approved in United States, European Union, Canada for the following indications:

Approved in United States as tDCS for:

• Stroke rehabilitation
• Motor disorders
• Neurological rehabilitation

Approved in European Union as tDCS for:

• Stroke rehabilitation
• Motor disorders
• Neurological rehabilitation

Approved in Canada as tDCS for:

• Stroke rehabilitation
• Motor disorders
• Neurological rehabilitation

Who Is Running the Clinical Trial?

Carle Foundation Hospital

Lead Sponsor

Trials

7

Recruited

720+

University of Oklahoma

Lead Sponsor

Trials

484

Recruited

95,900+

American Heart Association

Collaborator

Trials

352

Recruited

6,196,000+

Findings from Research

High-definition transcranial direct current stimulation (HD-tDCS) is feasible and acceptable for patients with chronic post-stroke aphasia, showing that it can be implemented effectively in a clinical setting with similar protocols to conventional sponge-based tDCS.

Preliminary results indicate that HD-tDCS may improve naming accuracy and response time in patients, with some evidence suggesting it could be more effective than conventional tDCS, although the differences were not statistically significant.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Feasibility of using high-definition transcranial direct current stimulation (HD-tDCS) to enhance treatment outcomes in persons with aphasia. Richardson, J., Datta, A., Dmochowski, J., et al.[2023]

Transcranial direct current stimulation (TDCS) applied to the affected hemisphere in 50 acute stroke patients was found to be safe, with no side effects reported during the treatment.

Despite being safe, the five daily sessions of anodal TDCS did not lead to significant improvements in motor deficits compared to sham treatment, indicating that TDCS may not enhance clinical outcomes in acute stroke patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial direct current stimulation of the affected hemisphere does not accelerate recovery of acute stroke patients. Rossi, C., Sallustio, F., Di Legge, S., et al.[2015]

The study involved 49 subacute stroke patients who participated in a 4-week robotic gait training program combined with transcranial direct current stimulation (tDCS), demonstrating that this combined approach is safe and feasible, with only one patient experiencing a minor side effect.

Despite improvements in gait speed and quality across all groups, the addition of tDCS targeting the leg motor cortex did not provide any additional benefits compared to robotic gait training alone or tDCS targeting the hand motor cortex.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

tDCS does not enhance the effects of robot-assisted gait training in patients with subacute stroke. Leon, D., Cortes, M., Elder, J., et al.[2018]

Transcranial direct current stimulation (tDCS) has shown promising results in enhancing motor learning and improving motor function in both healthy individuals and stroke patients, particularly when combined with targeted training.

tDCS is well tolerated and easy to use, with evidence suggesting that specific timing and electrode configurations can optimize its effectiveness for rehabilitation, although more acute studies in brain injury patients are needed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Modulation of motor performance and motor learning by transcranial direct current stimulation. Reis, J., Fritsch, B.[2022]

In a study involving 19 acute stroke patients with severe motor impairment, bihemispheric transcranial direct current stimulation (tDCS) combined with peripheral nerve stimulation did not show significant clinical or neurophysiological improvements compared to sham stimulation over a 12-month follow-up period.

Both treatment groups exhibited time-related changes in motor and sensory assessments, but there were no significant differences between the real and sham tDCS groups, suggesting that the severity of motor impairment may affect the efficacy of tDCS interventions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of Bihemispheric Transcranial Direct Current Stimulation Combined With Repetitive Peripheral Nerve Stimulation in Acute Stroke Patients. Yagüe, S., Veciana, M., Martínez-Yélamos, A., et al.[2023]

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]

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]

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]

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]

A systematic review of 64 studies involving 2262 participants found that transcranial direct current stimulation (tDCS) has a low dropout rate (6% for active and 7.2% for sham), indicating good acceptability among participants.

Despite the low dropout rates, many studies inadequately reported adverse events (AEs), highlighting a need for improved guidelines to standardize AE reporting in tDCS research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Systematic Review on the Acceptability and Tolerability of Transcranial Direct Current Stimulation Treatment in Neuropsychiatry Trials. Aparício, LVM., Guarienti, F., Razza, LB., et al.[2018]

Transcranial direct current stimulation (tDCS) using a new montage improved the detection of right-hand motor imagery in 4 out of 5 healthy volunteers when applied for 10 minutes at the highest current density over the right-hand motor area.

While changes in EEG band power were not directly linked to improved classification accuracy, the study suggests that tDCS can influence different motor areas, indicating potential for enhancing motor neurorehabilitation techniques.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of tDCS stimulation of motor cortex and cerebellum on EEG classification of motor imagery and sensorimotor band power. Angulo-Sherman, IN., Rodríguez-Ugarte, M., Sciacca, N., et al.[2018]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Feasibility of using high-definition transcranial direct current stimulation (HD-tDCS) to enhance treatment outcomes in persons with aphasia. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Transcranial direct current stimulation of the affected hemisphere does not accelerate recovery of acute stroke patients. [2015]

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

tDCS does not enhance the effects of robot-assisted gait training in patients with subacute stroke. [2018]

4. England pubmed.ncbi.nlm.nih.gov

Modulation of motor performance and motor learning by transcranial direct current stimulation. [2022]

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

Effects of Bihemispheric Transcranial Direct Current Stimulation Combined With Repetitive Peripheral Nerve Stimulation in Acute Stroke Patients. [2023]

6. 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]

7. 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]

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

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

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

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

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

A Systematic Review on the Acceptability and Tolerability of Transcranial Direct Current Stimulation Treatment in Neuropsychiatry Trials. [2018]

11. England pubmed.ncbi.nlm.nih.gov

Effect of tDCS stimulation of motor cortex and cerebellum on EEG classification of motor imagery and sensorimotor band power. [2018]