Transcranial Direct Current Stimulation for Cognitive Impairment in Multiple Sclerosis

(MS-HDtDCS Trial)

Overseen By Jill Ritter, BS

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: The University of Texas at Dallas

Must not be taking: Anti-convulsants, Stimulants, others

Disqualifiers: Dementia, Epilepsy, Stroke, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 22

Duration: 6 weeks

100 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of the study is to test whether low level electric stimulation, called transcranial Direct Current Stimulation (tDCS), on the part of the brain (i.e., presupplementary motor area) thought to aid in memory will improve verbal retrieval in multiple sclerosis patients. The primary outcome measures are neuropsychological assessments of verbal retrieval, and the secondary measures are neuropsychological assessments of other cognitive abilities and electroencephalography (EEG) measures. Additionally, the study will examine the degree to which baseline assessments of cognition and concussion history predict responses to treatment over time, both on assessments administered within the intervention period and at follow-up.

Will I have to stop taking my current medications?

You may need to stop taking certain medications that interact with the study treatment, such as stimulants like dextroamphetamine, amphetamine, modafinil, and armodafinil. If you are on benzodiazepines, you must have been on a stable dose for at least two months before joining the trial.

What data supports the effectiveness of the treatment High-Definition Transcranial Direct Current Stimulation for cognitive impairment in Multiple Sclerosis?

Research suggests that transcranial direct current stimulation (tDCS) may help improve cognitive functions in conditions like Alzheimer's disease and mild cognitive impairment, and it has been explored for cognitive issues in multiple sclerosis (MS). However, studies specifically on MS show mixed results, indicating a need for more research to confirm its effectiveness for cognitive improvement in MS patients. ^{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 no reports of serious adverse effects or irreversible injury in over 33,200 sessions across various populations, including potentially vulnerable groups. However, it can cause mild skin irritation, and there are concerns about potential risks, so caution is advised. ^{2 6 7 8 9}

How is transcranial direct current stimulation (tDCS) different from other treatments for cognitive impairment in multiple sclerosis?

Transcranial direct current stimulation (tDCS) is a unique, non-invasive brain stimulation technique that uses a mild electrical current to potentially improve cognitive functions in multiple sclerosis, unlike traditional drug treatments. It is still being studied for its effects on cognition, but it has shown promise in other conditions like Alzheimer's disease. ^{1 2 3 5 10}

Research Team

John Hart, Jr, MD

Principal Investigator

University of Texas at Dallas

Eligibility Criteria

This trial is for individuals with relapsing-remitting multiple sclerosis who have trouble retrieving words. They must speak and read English well, not have had a recent MS episode or taken steroids, and can't be on certain medications like benzodiazepines unless stable for two months.

Inclusion Criteria

Memory retrieval deficit based on neuropsychological testing done in our lab

Must be fluent in speaking and reading English.

I have been diagnosed with relapsing-remitting multiple sclerosis.

Exclusion Criteria

I am not taking any medication that could affect the study treatment.

I have been taking the same dose of benzodiazepines for at least two months.

I do not have any major brain-related health issues like dementia, epilepsy, or drug abuse.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive transcranial direct current stimulation (tDCS) or sham treatment for 20 minutes over 10 sessions

6 weeks

10 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with assessments at immediate and 2-month intervals

13 weeks

2 visits (in-person)

Second Round of Treatment (optional)

Selected participants receive a second round of tDCS or sham treatment, followed by immediate and 2-month follow-up assessments

6 weeks

10 visits (in-person)

Treatment Details

Interventions

• High-Definition Transcranial Direct Current Stimulation

Trial Overview The study tests if low-level electric brain stimulation (tDCS) improves word retrieval in MS patients. It compares real tDCS to sham (fake) treatment, measuring verbal skills before, during, after the treatment, and checks other cognitive abilities plus EEG readings.

Participant Groups

Group I: Transcranial direct current stimulation Experimental Treatment 1 Intervention

Transcranial direct current stimulation will be delivered via a Neuroelectrics Starstim tES. Stimulation will consist of 1 milliamp stimulation, with anodal stimulation delivered at electrode Fz (International 10/10 System for electroencephalography electrode placement) and electrodes F7, FP1, FP2, and F8 as returns. All electrodes are 1 cm diameter Ag/AgCl electrodes and make contact with the scalp via connective gel. Stimulation will linearly ramp up from 0 milliamps to 1 milliamp over 60 seconds, then remain at 1 milliamp of stimulation over 20 minutes, and finally ramping down at to 0 milliamps over 60 seconds. Other Names: tDCS 1 milliamp tDCS High definition tDCS High definition transcranial direct current stimulator, Neuroelectrics Starstim tES, SN E20200930-10

Group II: Sham transcranial direct current stimulation Placebo Group 1 Intervention

Sham transcranial direct current stimulation will be delivered via a Neuroelectrics Starstim tES. The sham setup will consist of anodal electrode Fz (International 10/10 System for electroencephalography electrode placement) and electrodes F7, FP1, FP2, and F8 as returns. All electrodes are 1 cm diameter Ag/AgCl electrodes and make contact with the scalp via connective gel. Stimulation will linearly ramp up from 0 milliamps to 1 milliamp over 60 seconds, ramp down to 0 milliamps over 60 seconds and then be left off for 20 minutes.

High-Definition Transcranial Direct Current Stimulation is already approved in United States, European Union for the following indications:

Approved in United States as tDCS for:

• Experimental treatment for cognitive deficits in multiple sclerosis

Approved in European Union as tDCS for:

• Experimental treatment for cognitive deficits in multiple sclerosis

Who Is Running the Clinical Trial?

The University of Texas at Dallas

Lead Sponsor

Trials

71

Recruited

108,000+

University of Texas Southwestern Medical Center

Collaborator

Trials

1,102

Recruited

1,077,000+

Findings from Research

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]

In a study involving 24 patients with multiple sclerosis, anodal transcranial direct current stimulation (tDCS) significantly improved cognitive functions, particularly reasoning and executive functions, compared to a sham treatment.

Despite the cognitive improvements, the study found no significant changes in resting-state brain electrical activity after the tDCS sessions, suggesting that while tDCS may enhance cognitive performance, its effects on brain activity need further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of transcranial direct current stimulation on cognitive dysfunction in multiple sclerosis. Gholami, M., Nami, M., Shamsi, F., et al.[2021]

Transcranial direct current stimulation (tDCS) is a safe and noninvasive method that shows promise in treating cognitive decline associated with Alzheimer's disease and mild cognitive impairment.

The review highlights the need for further large-scale clinical trials to better understand the mechanisms of tDCS and improve its application in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Potential of Transcranial Direct Current Stimulation in Alzheimer's Disease: Optimizing Trials Toward Clinical Use. Pilloni, G., Charvet, LE., Bikson, M., et al.[2022]

Anodal transcranial direct current stimulation (tDCS) applied to the left dorsolateral prefrontal cortex significantly improved cognitive tasks related to processing speed, selective attention, and planning in five older adults with mild cognitive impairment (MCI).

The study suggests that combining tDCS with cognitive stimulation programs may enhance cognitive performance in individuals with MCI, but further research is needed to explore long-term effects and practical applications in daily life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Effects of Transcranial Direct Current Stimulation on the Cognitive Functions in Older Adults with Mild Cognitive Impairment: A Pilot Study. Cruz Gonzalez, P., Fong, KNK., Brown, T.[2022]

In a small study of 11 patients with Multiple Sclerosis, transcranial direct current stimulation (tDCS) did not show significant improvements in general or social cognition, suggesting that this method may not be effective for cognitive enhancement in MS patients.

Interestingly, the study found that active tDCS might have impaired working memory performance, as indicated by a lack of improvement in the 1-Back test, highlighting the need for further research to understand the effects of tDCS on cognition in MS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of Transcranial Direct Current Stimulation on Information Processing Speed, Working Memory, Attention, and Social Cognition in Multiple Sclerosis. Grigorescu, C., Chalah, MA., Lefaucheur, JP., et al.[2020]

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]

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]

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]

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 14 patients with multiple sclerosis (MS) and 14 healthy controls, post-training transcranial direct current stimulation (tDCS) improved motor consolidation in healthy individuals but did not benefit MS patients, indicating a potential inefficiency in the motor consolidation network in MS.

Despite comparable learning speed during training, MS patients performed worse in functional motor tests, highlighting the need to understand disease-related mechanisms to enhance motor recovery strategies using non-invasive brain stimulation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Compromised tDCS-induced facilitation of motor consolidation in patients with multiple sclerosis. Rumpf, JJ., Dietrich, S., Stoppe, M., et al.[2018]

References

1. 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]

2. France pubmed.ncbi.nlm.nih.gov

Effects of transcranial direct current stimulation on cognitive dysfunction in multiple sclerosis. [2021]

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

Potential of Transcranial Direct Current Stimulation in Alzheimer's Disease: Optimizing Trials Toward Clinical Use. [2022]

4. Netherlands pubmed.ncbi.nlm.nih.gov

The Effects of Transcranial Direct Current Stimulation on the Cognitive Functions in Older Adults with Mild Cognitive Impairment: A Pilot Study. [2022]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Effects of Transcranial Direct Current Stimulation on Information Processing Speed, Working Memory, Attention, and Social Cognition in Multiple Sclerosis. [2020]

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

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

7. 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]

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

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

9. England pubmed.ncbi.nlm.nih.gov

Microdermabrasion facilitates direct current stimulation by lowering skin resistance. [2023]

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

Compromised tDCS-induced facilitation of motor consolidation in patients with multiple sclerosis. [2018]