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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new method to help people with mild cognitive impairment (MCI) or dementia improve memory and language skills. The study tests a device called NeuroElectric StarStim, which uses gentle brain stimulation (known as High-Definition Transcranial Direct Current Stimulation or HD-tDCS) to target specific brain areas involved in memory. Participants receive either active or sham (fake) stimulation over ten sessions and complete memory tests before and after the treatment. Individuals diagnosed with MCI or dementia who frequently experience memory issues may be well-suited for this trial. As an unphased trial, this study offers participants the chance to contribute to innovative research that could lead to new treatment options.

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 prior data suggests that this neurostimulation technique is safe for improving cognitive functions in dementia patients?

Research has shown that high-definition transcranial direct current stimulation (HD-tDCS) is generally safe. Earlier studies used HD-tDCS safely for up to 20 days, often improving thinking skills without major side effects. This brain stimulation employs a gentle electrical current to influence brain activity.

Participants in these studies found the treatment easy to handle. Side effects, if any, were usually mild, such as slight itching or tingling where the device was placed, and these effects typically resolved quickly.

Overall, the available data indicates that HD-tDCS, like the NeuroElectric StarStim device used in this study, is a safe option for those considering joining a clinical trial. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about NeuroElectric StarStim for dementia because it offers a novel approach by using non-invasive brain stimulation. Unlike current medications that often focus on chemical pathways, this treatment uses high-definition transcranial direct current stimulation (HD-tDCS) to target specific brain regions like the preSMA/dACC. This method aims to directly enhance cognitive functions such as word retrieval, potentially offering quicker improvements without the side effects commonly associated with drug therapies. Plus, the possibility of personalizing the stimulation to individual brain patterns makes it stand out as a promising alternative to traditional treatments.

What evidence suggests that this neurostimulation technique is effective for improving memory in dementia?

Research has shown that high-definition transcranial direct current stimulation (HD-tDCS) can enhance memory and thinking skills. One study found that people with mild memory problems learned and remembered better after HD-tDCS treatment. Another study discovered that this brain stimulation helped older adults think more clearly. The technique gently stimulates specific brain areas related to memory and word recall. In this trial, participants will receive either active HD-tDCS treatment or a sham treatment. Early findings suggest that HD-tDCS might benefit those with mild cognitive impairment or dementia. ^{1 6 7 8 9}

Are You a Good Fit for This Trial?

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.

All races/ethnicities

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

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]

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]

Citations

1.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/39863318/

High definition transcranial direct current stimulation as an ...

The primary outcome was change in total learning and delayed recall on the Rey Auditory Verbal Learning Test (RAVLT) immediately post-treatment and at 8-weeks.

2.

sciencedirect.com

sciencedirect.com/science/article/abs/pii/S1876201820306559

High definition transcranial direct current stimulation (HD- ...

The current article narratively reviews the mechanism of action of HD-tDCS, and it systematically examines the cognitive, clinical, and neurobiological effects ...

3.

nature.com

nature.com/articles/s41598-024-67664-9

Effects of transcranial direct current stimulation on ...

This study evaluates the cognitive effects of sequential tDCS on 63 mild cognitive impairment (MCI) patients, considering AD risk factors.

4.

gpsych.bmj.com

gpsych.bmj.com/content/36/6/e101166

Impact of twice-a-day transcranial direct current stimulation ...

Our research indicates for the first time that twice-a-day tDCS may improve the cognitive function of patients with AD.

5.

karger.com

karger.com/ger/article/70/5/544/898064/Effects-of-Transcranial-Direct-Current-Stimulation

Effects of Transcranial Direct Current Stimulation on ...

The results showed that tDCS enhanced the cognitive function of older adults with statistical significance (Z = 2.36, p = 0.02), and its effect ...

6.

clinicaltrials.gov

clinicaltrials.gov/study/NCT04599764

High Definition Transcranial Direct Current Stimulation (HD ...

Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation tool that alters cortical excitability and activity via application of weak ...

7.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC11040101/

Safety and feasibility of optimized transcranial direct current ...

Previous research has shown that tDCS can be safely used for 20 days and has significant effects on cognitive function (11, 12). Although there ...

8.

sciencedirect.com

sciencedirect.com/science/article/pii/S2324242625000129

Comparison of the efficacy of high-definition transcranial ...

All groups demonstrated significant improvement in depressive symptoms and cognitive function. The rTMS group exhibited a significantly greater decrease in ...

9.

physio-pedia.com

physio-pedia.com/Transcranial_Electrical_Nerve_Stimulation_for_Dementia

Transcranial Electrical Nerve Stimulation for Dementia

Current findings suggest that tDCS combined with Robotic Therapy (RT) does not improve upper limb function, strength, spasticity, functional independence or ...