Transcranial Direct Current Stimulation for Cognitive Impairment in Multiple Sclerosis

(MS-HDtDCS Trial)

Overseen By Jill Ritter, BS

Age: 18+

Sex: Any

Trial Phase: Academic

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether a mild electrical treatment called transcranial Direct Current Stimulation (tDCS) can improve memory in people with multiple sclerosis (MS). The main focus is on enhancing verbal recall, which involves remembering and using words. Participants will receive either the actual tDCS or a sham (inactive) version to determine if there's a noticeable benefit. Those diagnosed with relapsing-remitting multiple sclerosis (RRMS) who struggle with memory retrieval might be suitable for this trial. As an unphased study, this trial allows participants to contribute to valuable research that could lead to new insights into memory improvement for MS patients.

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 prior data suggests that transcranial direct current stimulation is safe for cognitive impairment in multiple sclerosis?

Research has shown that transcranial Direct Current Stimulation (tDCS) is a safe and well-tolerated treatment. Studies have found that this type of brain stimulation does not cause serious side effects. For instance, participants tolerated levels up to 4 milliamps well. This trial uses an even lower level of 1 milliamp, which previous studies have proven safe.

Individuals who have used tDCS report only mild side effects, such as slight tingling on the scalp or some skin redness, which are usually temporary and not harmful. This technique has even been used safely at home for conditions like multiple sclerosis, a disease affecting the brain and spinal cord.

Overall, evidence suggests that tDCS is a safe option for those considering joining this study. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about using High-Definition Transcranial Direct Current Stimulation (HD-tDCS) for cognitive impairment in multiple sclerosis because it offers a novel, non-invasive approach. Unlike traditional medications that often focus on symptom management through drug-based therapies, HD-tDCS directly targets brain activity by using mild electrical currents to potentially enhance neural connections and improve cognitive function. This method is particularly promising as it might offer a safer alternative with fewer side effects compared to pharmacological treatments. Additionally, the precision of HD-tDCS in targeting specific brain areas makes it a cutting-edge option that could lead to more personalized and effective treatment strategies for patients.

What evidence suggests that transcranial Direct Current Stimulation is effective for cognitive impairment in multiple sclerosis?

Research has shown that transcranial Direct Current Stimulation (tDCS) can improve thinking skills in people with multiple sclerosis (MS). In this trial, participants will receive either active tDCS or sham tDCS. One study found that tDCS improved thinking speed, mood, pain, and tiredness in MS patients. Another study suggested that tDCS might be more effective when combined with brain training exercises. Evidence also indicates that tDCS can help with thinking problems in conditions like schizophrenia and depression. Overall, tDCS appears to be a promising method for addressing thinking challenges in MS. ^{6 7 8 9 10}

Who Is on the Research Team?

John Hart, Jr, MD

Principal Investigator

University of Texas at Dallas

Are You a Good Fit for This Trial?

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 for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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) 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 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]

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 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]

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]

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]

Citations

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Transcranial Direct Current Stimulation for Cognitive ... Moreover, tDCS has been shown to be effective in treating cognitive dysfunction in conditions such as schizophrenia, multiple sclerosis, and major depression ( ...

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High-Definition Transcranial Direct Current Stimulation (HD ... Evidence suggests that anodal tDCS, unlike cathodal tDCS, can induce beneficial functional effects without accelerating the progression of Amyotrophic Lateral ...

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Effects of transcranial direct current stimulation on cognitive ... Anodal tDCS over the left DLPFC appears to be a promising therapeutic option for cognitive dysfunction in patients with MS.

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Home-based transcranial direct current stimulation paired ... A safe and well-tolerated type of noninvasive brain stimulation, is a low-cost and home-based approach with the potential to reduce fatigue in MS.

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Tolerability and blinding of high-definition transcranial ... HD-tDCS was well tolerated with center electrode amplitudes up to 4 mA. The bimodal ramp-up/down format of the sham was effective for blinding.

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Study Details | NCT03499314 | A Pilot Trial of Remotely- ... This is a randomized, double-blind pilot clinical trial to test a novel treatment approach to rehabilitate fine motor function in individuals living with ...

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Extended Multiple-Field High-Definition transcranial direct ... Extended Multiple-Field High-Definition transcranial direct current stimulation (HD-tDCS) is well tolerated and safe in healthy adults. Christopher A Turski ...