tDCS + Cognitive Training for Post-Stroke Cognitive Impairment

(TIPSCI Trial)

Overseen By Elisabeth B Marsh, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Johns Hopkins University

Disqualifiers: Dementia, Psychiatric illness, Aphasia, 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: 18

Duration: 5 weeks

60 Participants Needed

Trial Summary

What is the purpose of this trial?

The investigators will conduct a randomized, double-blinded, sham-controlled trial of approximately 60 patients with minor stroke and post-stroke mild cognitive impairment (psMCI). Participants will be individually randomized on enrollment using a random number generator to treatment with anodal tDCS + computerized cognitive treatment (CCT) versus sham + CCT (approximately 30 patients in each arm). Clinical evaluation including assessment of cognition will be performed pre- and post-intervention by individuals on the study team blinded to the participant's intervention. Participants will also undergo functional neuroimaging with magnetoencephalography (MEG) pre- and post-intervention (1, 3, and 6 months post-stroke to evaluate for initial and longer-term effects of treatment on cerebral activation patterns and functional connectivity). Neuroimaging and clinical outcomes will be assessed to determine the effect of tDCS versus sham + CCT on psMCI.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is the treatment Anodal transcranial Direct Current Stimulation (A-tDCS) combined with cognitive training effective for improving cognitive function in post-stroke patients?

Research shows that combining transcranial direct current stimulation (tDCS) with cognitive training can improve cognitive performance during the stimulation in healthy individuals, but the benefits do not necessarily lead to long-term learning improvements. In stroke patients, while cognitive training alone showed significant improvements, adding tDCS did not provide additional benefits. ^{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 studies showing no serious adverse effects in over 33,200 sessions across various populations, including potentially vulnerable groups. However, some reports suggest it could potentially cause significant conditions in healthy individuals, so caution is advised. ^{4 6 7 8 9}

How does the treatment Anodal tDCS differ from other treatments for post-stroke cognitive impairment?

Anodal tDCS is a non-invasive brain stimulation technique that uses a mild electrical current to enhance cognitive function, which is different from traditional drug-based treatments. It is often combined with cognitive training to potentially improve cognitive performance, although its effects can be less predictable and vary among individuals. ^{3 5 10 11 12}

Research Team

Elisabeth B Marsh, MD

Principal Investigator

Johns Hopkins University

Eligibility Criteria

This trial is for adults over 18 who've had a minor stroke within the last week and show mild cognitive issues afterward. They must speak English, have manageable stroke symptoms (NIHSS <8), and be relatively independent (mRS 0-2). People with dementia, severe psychiatric illness, or those unable to attend sessions are excluded.

Inclusion Criteria

Your stroke severity score is less than 8 at your first follow-up visit, which is about 30 days after the stroke.

I am an adult who had stroke symptoms start within the last week.

You have recently had a stroke shown on a brain MRI. Strokes that don't show up on imaging and transient ischemic attacks (TIAs) will also be excluded.

Exclusion Criteria

You have bleeding in your brain as shown by a head CT or MRI.

I have hearing or vision problems that haven't been corrected.

I have a major blood vessel blockage near my heart or brain.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 15 sessions of anodal tDCS or sham intervention over 5 weeks, combined with computerized cognitive therapy (CCT)

5 weeks

15 sessions (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with MEG and cognitive assessments at 1, 3, and 6 months post-stroke

6 months

3 visits (in-person)

Treatment Details

Interventions

• Anodal transcranial Direct Current Stimulation (A-tDCS)
• Sham Intervention

Trial Overview The study tests if anodal transcranial Direct Current Stimulation (A-tDCS) combined with computerized cognitive treatment improves cognition in post-stroke patients compared to a sham intervention. It's randomized and double-blinded, meaning participants won't know which treatment they're getting.

Participant Groups

Group I: A-tDCS Experimental Treatment 1 Intervention

Participants randomized to tDCS will undergo 15- 30 minute sessions over 5 weeks of A-tDCS to the ipsilesional frontoparietal cortex while participating in computerized cognitive therapy (CCT).

Group II: Sham Intervention Active Control 1 Intervention

Participants randomized to sham will undergo 15- 30 minute sessions over 5 weeks of a sham-intervention, also applied to the ipsilesional frontoparietal cortex, while participating in computerized cognitive therapy (CCT).

Anodal transcranial Direct Current Stimulation (A-tDCS) is already approved in United States, European Union, China for the following indications:

Approved in United States as Transcranial Direct Current Stimulation for:

• Post-stroke cognitive impairment
• Post-stroke depression
• Aphasia
• Central post-stroke pain

Approved in European Union as Transcranial Direct Current Stimulation for:

• Post-stroke cognitive impairment
• Post-stroke depression
• Aphasia
• Central post-stroke pain

Approved in China as Transcranial Direct Current Stimulation for:

• Post-stroke cognitive impairment
• Post-stroke depression
• Aphasia
• Central post-stroke pain

Who Is Running the Clinical Trial?

Johns Hopkins University

Lead Sponsor

Trials

2,366

Recruited

15,160,000+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

University of Maryland, College Park

Collaborator

Trials

163

Recruited

46,800+

Findings from Research

In a study involving 11 newly diagnosed stroke patients, the combination of transcranial direct current stimulation (tDCS) and computer-assisted cognitive rehabilitation (CACR) significantly improved cognitive function compared to a control group receiving sham stimulation.

Patients receiving tDCS showed notable enhancements in auditory and visual continuous performance tests, suggesting that targeting the prefrontal cortex with tDCS alongside cognitive training can effectively aid recovery from cognitive dysfunction after a stroke.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A double-blind, sham-controlled, pilot study to assess the effects of the concomitant use of transcranial direct current stimulation with the computer assisted cognitive rehabilitation to the prefrontal cortex on cognitive functions in patients with stroke. Park, SH., Koh, EJ., Choi, HY., et al.[2022]

In a study of 45 stroke patients with cognitive dysfunction, anodal transcranial direct-current stimulation (tDCS) applied to the left anterior temporal lobe significantly improved verbal learning abilities compared to sham stimulation.

Despite improvements in verbal learning, there were no significant changes in overall cognitive function or daily living activities as measured by the K-MMSE and K-MBI, suggesting that tDCS may specifically enhance certain cognitive aspects rather than overall cognitive performance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Effects of Transcranial Direct-Current Stimulation on Cognition in Stroke Patients. Yun, GJ., Chun, MH., Kim, BR.[2020]

Transcranial direct current stimulation (tDCS) combined with cognitive training significantly improved executive function and performance in daily activities among 50 stroke patients, as measured by various cognitive tests.

While most cognitive assessments showed significant improvements in the tDCS group compared to the sham group, some specific tasks related to daily living did not show notable differences, indicating that tDCS may be more effective for certain cognitive functions than others.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Explore combined use of transcranial direct current stimulation and cognitive training on executive function after stroke. Liu, YW., Chen, ZH., Luo, J., et al.[2022]

In a study involving 60 healthy participants, those who received active transcranial direct current stimulation (tDCS) combined with cognitive training (CT) showed improved accuracy on cognitive tasks compared to those who received sham tDCS, indicating that tDCS can enhance cognitive performance during training.

At a 4-week follow-up, participants who had the active tDCS combined with CT demonstrated greater improvements in attention and working memory on non-trained tasks compared to those who only received tDCS, suggesting that tDCS may enhance the benefits of cognitive training beyond the immediate task.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Can transcranial direct current stimulation enhance outcomes from cognitive training? A randomized controlled trial in healthy participants. Martin, DM., Liu, R., Alonzo, A., et al.[2022]

In a study involving 77 chronic stroke patients, combining computerized cognitive training (CCT) with transcranial direct current stimulation (tDCS) led to significant improvements in cognitive performance, but tDCS did not provide any additional benefits over CCT alone.

fMRI results indicated that improved cognitive performance was linked to increased brain activation in areas associated with attention, but there was no clear relationship between initial brain activation levels and cognitive gains, suggesting that the training itself was effective regardless of tDCS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reliability, sensitivity, and predictive value of fMRI during multiple object tracking as a marker of cognitive training gain in combination with tDCS in stroke survivors. Kolskår, KK., Richard, G., Alnaes, D., et al.[2022]

Transcranial direct current stimulation (tDCS) was found to enhance working memory and learning potential in a study of 31 healthy older adults, with 16 receiving actual stimulation and 15 receiving a sham treatment.

The study demonstrated that tDCS is a safe and non-invasive method for improving cognitive functions in older adults, although it did not show significant effects on immediate memory.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enhancing Immediate Memory, Potential Learning, and Working Memory with Transcranial Direct Current Stimulation in Healthy Older Adults. Satorres, E., Meléndez, JC., Pitarque, A., et al.[2023]

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) 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]

In a study involving 39 healthy young adults, repeated sessions of anodal high-definition transcranial direct current stimulation (HD-tDCS) over 4 weeks significantly improved executive control and psychomotor efficiency, with benefits increasing over time.

Unlike the sham group, which showed a return to baseline performance after 9 sessions, the anodal group maintained their improvements in attention, suggesting that repeated HD-tDCS has a cumulative positive effect on cognitive function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Modulation of Repeated Anodal HD-tDCS on Attention in Healthy Young Adults. Lu, H., Liu, Q., Guo, Z., et al.[2020]

Anodal transcranial direct current stimulation (a-tDCS) significantly improved cognitive functions in multiple sclerosis (MS) patients compared to a sham treatment, with effects persisting for some tasks during follow-up.

While cognitive training alone showed immediate benefits in attention and inhibitory control, these improvements did not last, indicating that a-tDCS may be a more effective long-term intervention for enhancing cognitive performance in MS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effectiveness of anodal tDCS and cognitive training on cognitive functions in multiple sclerosis; a randomized, double-blind, parallel-group study. Simani, L., Roozbeh, M., Shojaei, M., et al.[2023]

Transcranial direct current stimulation (tDCS) is a safe and affordable neuromodulatory technique that shows potential for modulating cognitive functioning, particularly in longitudinal studies where repeated sessions are used.

While tDCS has demonstrated some cognitive benefits, the effects are less consistent compared to its impact on motor outcomes, and more research is needed to understand the mechanisms behind its efficacy and to identify which individuals respond best to the treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cognitive Effects of Transcranial Direct Current Stimulation in Healthy and Clinical Populations: An Overview. Berryhill, ME., Martin, D.[2019]

References

1. Korea (South) pubmed.ncbi.nlm.nih.gov

A double-blind, sham-controlled, pilot study to assess the effects of the concomitant use of transcranial direct current stimulation with the computer assisted cognitive rehabilitation to the prefrontal cortex on cognitive functions in patients with stroke. [2022]

2. Korea (South) pubmed.ncbi.nlm.nih.gov

The Effects of Transcranial Direct-Current Stimulation on Cognition in Stroke Patients. [2020]

3. Sweden pubmed.ncbi.nlm.nih.gov

Explore combined use of transcranial direct current stimulation and cognitive training on executive function after stroke. [2022]

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

Can transcranial direct current stimulation enhance outcomes from cognitive training? A randomized controlled trial in healthy participants. [2022]

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

Reliability, sensitivity, and predictive value of fMRI during multiple object tracking as a marker of cognitive training gain in combination with tDCS in stroke survivors. [2022]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Enhancing Immediate Memory, Potential Learning, and Working Memory with Transcranial Direct Current Stimulation in Healthy Older Adults. [2023]

7. 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]

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. Switzerland pubmed.ncbi.nlm.nih.gov

Modulation of Repeated Anodal HD-tDCS on Attention in Healthy Young Adults. [2020]

11. Netherlands pubmed.ncbi.nlm.nih.gov

The effectiveness of anodal tDCS and cognitive training on cognitive functions in multiple sclerosis; a randomized, double-blind, parallel-group study. [2023]

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

Cognitive Effects of Transcranial Direct Current Stimulation in Healthy and Clinical Populations: An Overview. [2019]