Brain Stimulation for Dementia

(COBALT Trial)

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Texas Southwestern Medical Center

Must not be taking: Medications altering HD-tDCS

Disqualifiers: Epilepsy, Brain tumor, Substance use, others

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 20

9999 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a pilot study being done to attempt to improve episodic memory problems in persons with mild cognitive impairment (MCI) or dementia. The pre-supplemental motor area (preSMA) and dorsal anterior cingulate cortex (dACC) have been shown to play a role in episodic memory and language retrieval. Prior studies have suggested that neurostimulation targeting this region can improve episodic memory and word recall. The purpose of this study is to examine the efficacy of high-definition transcranial direct current stimulation (HD-tDCS) to the preSMA/dACC region and its influence on word retrieval and other cognitive functions in patients with MCI or dementia. Entraining the preSMA/dACC circuit with 10 sessions of HD-tDCS will allow us to study whether neurostimulation may be an effective treatment.

Will I have to stop taking my current medications?

The trial excludes participants who are currently using medications known to alter the effects of the brain stimulation treatment. If you're on such medications, you may need to stop taking them to participate.

What data supports the effectiveness of the treatment NeuroElectric StarStim, HD-tDCS, Transcranial Direct Current Stimulation, High-Definition tDCS for dementia?

Research suggests that transcranial direct current stimulation (tDCS) may help improve cognitive performance and slow cognitive decline in Alzheimer's disease, a type of dementia. Studies have shown that combining tDCS with cognitive exercises can enhance brain activity and cognitive function in patients with Alzheimer's. ^{1 2 3 4 5}

Is brain stimulation for dementia safe for humans?

Transcranial Direct Current Stimulation (tDCS), including its high-definition version, is generally considered safe in humans, with no serious adverse effects reported in over 33,200 sessions across various populations, including potentially vulnerable groups like the elderly. However, some studies suggest it may cause skin irritation or other minor, temporary side effects. ^{6 7 8 9 10}

How is the NeuroElectric StarStim treatment different from other dementia treatments?

NeuroElectric StarStim, or HD-tDCS, is unique because it uses high-definition transcranial direct current stimulation to specifically target brain areas, potentially improving cognitive function by altering brain activity and connectivity without the side effects of drugs. ^{2 3 11 12 13}

Eligibility Criteria

This trial is for individuals aged 55 or older who are fluent in English and have been diagnosed with mild cognitive impairment or dementia. It's open to all genders and ethnicities. People can't join if they've had major neurological conditions, substance use disorders within the last year, metal fragments in their head, sensory impairments affecting testing, or take medications that affect brain stimulation.

Inclusion Criteria

I have been diagnosed with mild cognitive impairment or dementia.

I am either a man or a woman.

I am 55 years old or older.

Exclusion Criteria

I am taking medication that affects brain stimulation treatments.

Substance use disorder within the past year

Has metal fragments in skull/head

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Phase 1

Participants receive 10 sessions of active or sham HD-tDCS targeting preSMA/dACC over 2 weeks

2 weeks

10 visits (in-person)

Follow-up Phase 1

Participants complete word retrieval and cognitive tasks immediately after session 10 and at a 2-month follow-up

2 months

Treatment Phase 2

Participants from the sham group receive 10 sessions of active HD-tDCS after 2 months

2 weeks

10 visits (in-person)

Follow-up Phase 2

Participants complete word retrieval and cognitive tasks immediately after the last HD-tDCS session and at a 2-month follow-up

2 months

Treatment Details

Interventions

• NeuroElectric StarStim

Trial Overview The study tests whether a brain stimulation device called NeuroElectric StarStim can improve memory and language in people with memory problems due to MCI or dementia. Participants will receive either real neurostimulation targeting specific brain areas or a sham (fake) treatment as part of the research.

Participant Groups

Group I: Phase 2: Active Treatment Active Control 1 Intervention

For Phase 2, participants randomized into the sham group will have the opportunity to return after 2 months from completing Phase 1. They will receive the active treatment while being unblinded to their treatment condition. Following 10 active treatment sessions, word retrieval and other cognitive tasks will again be completed immediately following the last HD-tDCS session and then a 2-month follow-up.

Group II: Phase 1: Active Treatment Active Control 1 Intervention

Participants will receive 10 sessions of active stimulation (1 mA anodal HD-tDCS targeting preSMA/dACC for 20 min) across 2 weeks. Word retrieval and other cognitive tasks will be completed at baseline, immediate follow-up after session 10, and a 2-month follow-up

Group III: Phase 1: Sham Treatment Placebo Group 1 Intervention

Participants will receive 10 sessions of sham stimulation across 2 weeks. Word retrieval and other cognitive tasks will be completed at baseline, immediate follow-up after session 10, and a 2-month follow-up

NeuroElectric StarStim is already approved in United States for the following indications:

Approved in United States as NeuroElectric StarStim for:

• Investigational for mild cognitive impairment (MCI) and dementia

Who Is Running the Clinical Trial?

University of Texas Southwestern Medical Center

Lead Sponsor

Trials

1,102

Recruited

1,077,000+

Texas Alzheimer's Research and Care Consortium

Collaborator

Trials

4

Recruited

10,100+

TEXAS ALZHEIMER'S RESEARCH & CARE CONSORTIUM

Collaborator

Trials

1

Recruited

10,000+

Findings from Research

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]

A meta-analysis of 4 studies found that transcranial direct current stimulation (tDCS) alone did not significantly improve the naming ability of patients with dementia.

However, when tDCS was combined with language or cognitive training, it resulted in a large effect size (SMD=0.72), indicating a significant improvement in naming ability for dementia patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined Effects of tDCS and Language/Cognitive Intervention on the Naming of Dementia Patients: A Systematic Review and Meta-Analysis. Byeon, H.[2022]

Anodal transcranial direct current stimulation (tDCS) significantly improved cognitive performance in healthy elderly individuals by increasing neural activity, as evidenced by enhanced P200 and P300 amplitudes during a working memory task.

Cathodal tDCS also showed potential benefits for Alzheimer's disease patients, increasing P200 amplitude and frontal theta activity, suggesting that tDCS can modulate neural function differently based on the individual's cognitive state.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Behavioural and electrophysiological modulations induced by transcranial direct current stimulation in healthy elderly and Alzheimer's disease patients: A pilot study. Cespón, J., Rodella, C., Miniussi, C., et al.[2020]

In a study involving 36 patients with Alzheimer's disease, multisite anodal transcranial direct current stimulation (tDCS) combined with cognitive stimulation significantly delayed cognitive decline compared to a sham treatment, as measured by the ADAS-cog scale.

The active tDCS+CS group showed greater changes in EEG coherence, indicating enhanced brain activity, which correlated with improvements in cognitive performance, suggesting that this combined approach may effectively modulate brain function in Alzheimer's patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of multisite anodal transcranial direct current stimulation combined with cognitive stimulation in patients with Alzheimer's disease and its neurophysiological correlates: A double-blind randomized clinical trial. Andrade, SM., Machado, DGDS., Silva-Sauerc, LD., et al.[2022]

In a study involving 34 Alzheimer's disease patients, both anodal and cathodal transcranial direct current stimulation (tDCS) significantly improved cognitive function as measured by the mini-mental state examination (MMSE) compared to sham stimulation.

tDCS also reduced the P300 latency, a measure associated with cognitive processing, indicating potential benefits in neurorehabilitation for Alzheimer's patients, although it did not affect motor cortex excitability.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A double-blind randomized clinical trial on the efficacy of cortical direct current stimulation for the treatment of Alzheimer's disease. Khedr, EM., Gamal, NF., El-Fetoh, NA., 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]

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]

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]

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]

Transcranial direct current stimulation (tDCS) is gaining recognition as a potential treatment method, especially for individuals who do not respond to or cannot tolerate traditional medications.

The review suggests that large controlled studies should be conducted within the National Health Service (NHS) to further explore the efficacy and practical applications of tDCS in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial stimulation in depression. Allan, C., Kalu, UG., Sexton, CE., et al.[2021]

Transcranial direct current stimulation (tDCS) shows promise as a non-invasive treatment for Alzheimer's disease (AD) by improving cognitive functions such as working and visual recognition memory, based on its ability to alter neuronal activity and cerebral blood flow.

tDCS may also have beneficial effects on other types of dementia, suggesting its potential as a versatile therapeutic tool, but further large-scale studies are needed to confirm its efficacy and mechanisms in various dementia disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Action mechanisms of transcranial direct current stimulation in Alzheimer's disease and memory loss. Hansen, N.[2021]

The novel high-definition transcranial direct current stimulation (HD-tDCS) setup was found to be safe and well-tolerated, with fewer adverse effects compared to conventional tDCS, based on a study involving 60 healthy participants.

HD-tDCS significantly improved cognitive performance on a visual task, indicating its potential for more effective neural modulation, while also being compatible with simultaneous fMRI without causing significant heating or image quality issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, Tolerability, Blinding Efficacy and Behavioural Effects of a Novel MRI-Compatible, High-Definition tDCS Set-Up. Gbadeyan, O., Steinhauser, M., McMahon, K., et al.[2022]

References

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

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Combined Effects of tDCS and Language/Cognitive Intervention on the Naming of Dementia Patients: A Systematic Review and Meta-Analysis. [2022]

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Behavioural and electrophysiological modulations induced by transcranial direct current stimulation in healthy elderly and Alzheimer's disease patients: A pilot study. [2020]

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Effects of multisite anodal transcranial direct current stimulation combined with cognitive stimulation in patients with Alzheimer's disease and its neurophysiological correlates: A double-blind randomized clinical trial. [2022]

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A double-blind randomized clinical trial on the efficacy of cortical direct current stimulation for the treatment of Alzheimer's disease. [2022]

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

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

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

9. 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]

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

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Transcranial stimulation in depression. [2021]

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Action mechanisms of transcranial direct current stimulation in Alzheimer's disease and memory loss. [2021]

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Safety, Tolerability, Blinding Efficacy and Behavioural Effects of a Novel MRI-Compatible, High-Definition tDCS Set-Up. [2022]