Electrical Stimulation for Post-Stroke Fatigue

Overseen By Hui-Ting Goh

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Texas Woman's University

Must not be taking: Fatigue medications

Disqualifiers: Acute medical problems, Depression, others

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

Compensation: Varies

Number of Visits: 7

Duration: 1 week

32 Participants Needed

Trial Summary

What is the purpose of this trial?

The goal of this phase I/II clinical trial is to determine the behavioral and neural effects of 5-daily transcranial direct current stimulation on post-stroke fatigue. The three aims are: Aim 1: Investigate the behavioral effect of 5 daily sessions of anodal tDCS over the ipsilesional M1 on PSF. Aim 2: Investigate the neurophysiological effect of 5 daily sessions of anodal tDCS over the ipsilesional M1. Aim 3: Determine the relationship between changes in M1 excitability, brain connectivity and changes in PSF. Participants will receive either a real or sham stimulation for 5 consecutive days and fatigue will be assessed before, immediately after and 1-month after the intervention. Fatigue will be assessed using clinical, behavioral, and neurophysiological outcomes.

Will I have to stop taking my current medications?

Yes, you may need to stop taking medications that affect your level of fatigue, as they are listed in the exclusion criteria for the trial.

What data supports the effectiveness of the treatment for post-stroke fatigue?

Research suggests that transcranial direct current stimulation (tDCS) may help reduce fatigue in conditions like multiple sclerosis, which shares similar fatigue symptoms with post-stroke fatigue. This indicates potential benefits of tDCS for post-stroke fatigue, although direct evidence is still being explored. ^{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 across thousands of sessions. Common mild side effects include itching, tingling, and headaches, but these are not significantly different from those experienced with placebo treatments. ^{4 6 7 8 9}

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

Anodal transcranial direct current stimulation (tDCS) is unique because it is a non-invasive brain stimulation technique that may help reduce fatigue by enhancing brain activity, unlike other treatments that might not directly target brain function. Currently, there are no effective standard treatments for post-stroke fatigue, making tDCS a novel option to explore. ^{1 4 5 10 11}

Research Team

Hui-Ting Goh

Principal Investigator

Physical Therapy

Eligibility Criteria

This trial is for adults who've had a stroke at least 3 months ago, can follow simple instructions, and experience significant fatigue (scoring ≥4 on the Fatigue Severity Scale). They should be able to move their affected arm somewhat. People with acute health issues, contraindications to the study's procedures, severe depression, pain that affects arm movement or medications influencing fatigue levels cannot participate.

Inclusion Criteria

I had a stroke more than 3 months ago.

I can move my arm enough to reach out for things.

You have a high average score on the Fatigue Severity Scale (FSS).

Exclusion Criteria

Acute medical problems

You have any reasons why you should not have tDCS, MRI, or TMS.

I have significant depression, scoring over 10 on a depression scale.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either real or sham transcranial direct current stimulation (tDCS) for 5 consecutive days

1 week

5 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with assessments at baseline, immediately after intervention, and 1 month after

4 weeks

2 visits (in-person)

Treatment Details

Interventions

• Anodal transcranial direct current stimulation
• Sham transcranial direct current stimulation

Trial Overview The study tests if anodal transcranial direct current stimulation (tDCS) over part of the brain affected by stroke can reduce post-stroke fatigue. Participants will get either real or sham tDCS daily for five days. The effects on behavior and brain function are assessed before, right after treatment and one month later.

Participant Groups

Group I: Anodal tDCS group Experimental Treatment 1 Intervention

Participants will receive anodal tDCS applied to the ipsilesional primary motor cortex.

Group II: Sham tDCS Placebo Group 1 Intervention

Participants will receive sham tDCS applied to the ipsilesional primary motor cortex

Anodal transcranial direct current stimulation is already approved in United States, European Union, Canada, China for the following indications:

Approved in United States as Transcranial Direct Current Stimulation for:

• Post-stroke fatigue
• Depression
• Chronic pain

Approved in European Union as Transcranial Direct Current Stimulation for:

• Post-stroke fatigue
• Depression
• Chronic pain
• Multiple sclerosis-related fatigue

Approved in Canada as Transcranial Direct Current Stimulation for:

• Post-stroke fatigue
• Depression
• Chronic pain

Approved in China as Transcranial Direct Current Stimulation for:

• Post-stroke fatigue
• Depression
• Chronic pain

Who Is Running the Clinical Trial?

Texas Woman's University

Lead Sponsor

Trials

90

Recruited

5,900+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Collaborator

Trials

2,103

Recruited

2,760,000+

Findings from Research

In a study involving 19 stroke survivors, transcranial direct current stimulation (tDCS) applied to the left dorsolateral prefrontal cortex did not significantly increase the number of completed rehabilitation therapy sessions compared to sham treatment.

Despite being well tolerated, tDCS did not show an effect on participation in rehabilitation, indicating that it may not be an effective intervention for enhancing therapy session completion in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial Direct Current Stimulation to Optimise Participation in Stroke Rehabilitation - A Sham-Controlled Cross-Over Feasibility Study. Etherton-Beer, C., Lui, Y., Radalj, M., et al.[2022]

Transcranial direct current stimulation (tDCS) has been shown to be a promising treatment for depression and fatigue in Multiple Sclerosis, with a meta-analysis of 18 high-quality randomized controlled trials indicating it is moderately to highly recommendable due to its effectiveness and negligible side effects.

The study utilized the GRADE criteria and PICO model to evaluate tDCS treatments, highlighting its low-cost and easy-to-use nature, which supports its potential inclusion in medical therapies for conditions related to brain electrical activity imbalances.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

tDCS randomized controlled trials in no-structural diseases: a quantitative review. Gianni, E., Bertoli, M., Simonelli, I., et al.[2021]

Transcranial direct current stimulation (tDCS) has shown positive effects in reducing fatigue symptoms in patients with multiple sclerosis (MS), particularly cognitive fatigue, based on a systematic review of 8 studies.

Most studies reported no serious side effects from tDCS, suggesting it is a safe intervention; however, the variability in treatment protocols and short follow-up periods indicate the need for larger, more standardized studies to confirm its efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of tDCS on the fatigue in patients with multiple sclerosis: A systematic review of randomized controlled clinical trials. Ashrafi, A., Mohseni-Bandpei, MA., Seydi, M.[2020]

Transcranial direct current stimulation (tDCS) significantly reduced post-stroke fatigue in 60 patients after 4 weeks of treatment, showing better results compared to the control group that received sham tDCS.

tDCS also improved motor function and daily activity ability, indicating its potential as a safe and effective treatment for enhancing recovery in stroke patients, although the benefits in fatigue did not persist at the 8-week follow-up.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized controlled trial to explore the efficacy and safety of transcranial direct current stimulation on patients with post-stroke fatigue. Dong, XL., Sun, X., Sun, WM., et al.[2023]

In a study involving multiple sclerosis patients with fatigue, five days of anodal transcranial direct current stimulation (tDCS) did not significantly change overall fatigue scores for the group, indicating limited efficacy in the general population.

However, a subgroup analysis revealed that patients with higher lesion loads in the left frontal cortex responded better to tDCS, suggesting that this treatment may be beneficial for specific patients with identifiable brain changes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of transcranial direct current stimulation on fatigue in multiple sclerosis. Saiote, C., Goldschmidt, T., Timäus, C., et al.[2015]

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, with mild and transient adverse effects reported in clinical trials, but the frequency and relationship of these effects with clinical variables remain unclear due to selective reporting bias.

Out of 209 studies reviewed, 117 mentioned adverse effects, with common issues like itching and tingling reported more frequently in the active tDCS group, although these differences were not statistically significant.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A systematic review on reporting and assessment of adverse effects associated with transcranial direct current stimulation. Brunoni, AR., Amadera, J., Berbel, B., et al.[2022]

Transcranial direct current stimulation (tDCS) was found to be feasible and safe for use in outpatient therapy for stroke patients, with 100% adherence among the 7 participants who completed the study over 5-6 weeks.

Most participants (71%) reported positive impressions of tDCS, experiencing acute improvements in function and energy, with only one adverse event unrelated to the treatment and mild side effects reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Feasibility and Safety of Transcranial Direct Current Stimulation in an Outpatient Rehabilitation Setting After Stroke. Cleland, BT., Galick, M., Huckstep, A., et al.[2020]

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]

In a study involving 10 patients with multiple sclerosis, anodal transcranial direct current stimulation (tDCS) significantly reduced fatigue by an average of 26%, demonstrating its potential efficacy as a non-pharmacological treatment.

The results suggest that targeting the primary somatosensory areas with personalized tDCS can effectively alleviate fatigue symptoms in mildly disabled MS patients, improving their quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multiple sclerosis fatigue relief by bilateral somatosensory cortex neuromodulation. Tecchio, F., Cancelli, A., Cottone, C., et al.[2021]

In a study involving 74 chronic stroke patients, six sessions of transcranial direct current stimulation (tDCS) combined with cognitive training did not show any additional benefits in reducing fatigue and depression symptoms compared to a sham treatment.

The analysis indicated that while fatigue and depression symptoms decreased during the intervention, the lack of added benefit from tDCS suggests that fatigue is a significant clinical concern that may affect treatment adherence and outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

No add-on effect of tDCS on fatigue and depression in chronic stroke patients: A randomized sham-controlled trial combining tDCS with computerized cognitive training. Ulrichsen, KM., Kolskår, KK., Richard, G., et al.[2022]

References

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

Transcranial Direct Current Stimulation to Optimise Participation in Stroke Rehabilitation - A Sham-Controlled Cross-Over Feasibility Study. [2022]

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

tDCS randomized controlled trials in no-structural diseases: a quantitative review. [2021]

3. Scotland pubmed.ncbi.nlm.nih.gov

The effect of tDCS on the fatigue in patients with multiple sclerosis: A systematic review of randomized controlled clinical trials. [2020]

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

A randomized controlled trial to explore the efficacy and safety of transcranial direct current stimulation on patients with post-stroke fatigue. [2023]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Impact of transcranial direct current stimulation on fatigue in multiple sclerosis. [2015]

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

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

7. England pubmed.ncbi.nlm.nih.gov

A systematic review on reporting and assessment of adverse effects associated with transcranial direct current stimulation. [2022]

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

Feasibility and Safety of Transcranial Direct Current Stimulation in an Outpatient Rehabilitation Setting After Stroke. [2020]

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

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

10. Germany pubmed.ncbi.nlm.nih.gov

Multiple sclerosis fatigue relief by bilateral somatosensory cortex neuromodulation. [2021]

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

No add-on effect of tDCS on fatigue and depression in chronic stroke patients: A randomized sham-controlled trial combining tDCS with computerized cognitive training. [2022]