Noninvasive Brain Stimulation for Alzheimer's Disease

Overseen By Robert M. G. Reinhart, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Boston University Charles River Campus

Must be taking: Cholinesterase inhibitors

Disqualifiers: Stroke, Traumatic brain injury, 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: Unknown

Duration: 1 year

204 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new, drug-free method to improve memory in people with Alzheimer's Disease (AD). Researchers are testing high-definition transcranial electrical current stimulation, a noninvasive brain stimulation technique, to determine if it can enhance memory by improving brain activity patterns. Participants with mild Alzheimer's dementia or mild cognitive impairment due to Alzheimer's, who face daily challenges like memory problems or difficulty with tasks they once performed easily, might be suitable candidates. The trial includes different groups: one receiving active stimulation and another receiving a sham (inactive) treatment for comparison. As an unphased trial, this study offers participants a unique opportunity to contribute to innovative research that could lead to new, non-drug treatments for Alzheimer's.

Will I have to stop taking my current medications?

The trial allows participants to continue taking certain medications, including antidepressants, Alzheimer's medications, and various heart and blood pressure medications. However, if you are on medications not listed, it's best to check with the trial coordinators.

What prior data suggests that high definition transcranial electrical current stimulation is safe for Alzheimer's patients?

Research shows that high-definition transcranial electrical current stimulation is generally well-tolerated by patients. Studies have demonstrated that this non-invasive brain treatment is safe for people with Alzheimer's disease. For instance, one study found that patients experienced memory improvements with minimal reports of discomfort or side effects.

Another review highlighted that this treatment safely addresses cognitive issues, such as memory problems, in Alzheimer's patients. Participants in these studies reported few negative effects, suggesting the treatment is safe for most people. This information should reassure potential participants about the safety of this approach as researchers explore its benefits for memory improvement. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about high definition transcranial electrical current stimulation for Alzheimer's because it offers a noninvasive approach to potentially enhancing memory. Unlike current treatments, which often rely on medications like cholinesterase inhibitors and NMDA receptor antagonists, this method uses electrical currents to directly stimulate brain activity. This technique could offer a new way to improve cognitive function without the side effects associated with drugs. Plus, as a noninvasive method, it might be more accessible and less intimidating for patients.

What evidence suggests that high definition transcranial electrical current stimulation is effective for Alzheimer's disease?

Research has shown that high definition transcranial electrical current stimulation (HD-tDCS) might improve thinking and memory in people with Alzheimer's disease. Some studies found that memory improves after this treatment, particularly in tasks like learning and recalling new information. However, not all studies have identified significant differences between real and sham stimulation. In this trial, participants will receive either active HD-tDCS or sham stimulation to further investigate its effectiveness. While promising, more research is necessary to confirm its efficacy. Currently, HD-tDCS represents an exciting avenue for non-drug treatments in Alzheimer's. ^{1 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for people aged 50-100 with Alzheimer's or mild cognitive impairment due to Alzheimer's, having certain memory performance scores. Healthy individuals can join if they meet specific cognitive norms. Participants must not have severe mental health issues, significant past brain conditions, or be on excluded medications.

Inclusion Criteria

Do you have a diagnosis of Mild Cognitive Impairment or Alzheimer's disease?

Exclusion Criteria

Have you ever had a diagnosis of epilepsy, or do you have current or past history of seizures?

Do you have a history of neurological problems such as stroke or head injury such as traumatic brain injury?

Do you have any skin sensitivity on your face or scalp (the study involves placing a fabric cap, several electrodes and some water-soluble gel at these sites)?

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive low-intensity, high-definition, transcranial electrical current stimulation while performing computer-based tasks

1 year

Follow-up

Participants are monitored for memory performance and cognitive function after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• High definition transcranial electrical current stimulation

Trial Overview

The study tests whether noninvasive brain stimulation using high definition transcranial electrical current can improve memory in those with Alzheimer's by affecting rhythmic activity in the brain. It aims to pave the way for drug-free treatments.

How Is the Trial Designed?

Group I: active stimulation Experimental Treatment 1 Intervention

Memory performance data is collected during active brain stimulation and reported 1 year later

Group II: sham stimulation Placebo Group 1 Intervention

Memory performance data is collected during sham brain stimulation and reported 1 year later

Who Is Running the Clinical Trial?

Boston University Charles River Campus

Lead Sponsor

Trials

125

Recruited

14,100+

Published Research Related to This Trial

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]

This study involves 100 older adults with mild-to-moderate Alzheimer's disease and investigates the effects of 6 months of at-home transcranial direct current stimulation (tDCS) on cognitive performance and other outcomes.

The trial aims to provide robust evidence on the safety and efficacy of tDCS as a treatment for Alzheimer's symptoms, addressing limitations of previous studies that had smaller sample sizes and shorter stimulation durations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neurostimulation for cognitive enhancement in Alzheimer's disease (the NICE-AD study): a randomized clinical trial. Gulley, E., Verghese, J., Blumen, HM., et al.[2022]

High-Definition transcranial Direct Current Stimulation (HD-tDCS) at amplitudes up to 4 mA was well tolerated by 292 older adults, with no safety-related adverse events reported and mostly mild sensations experienced during sessions.

The study demonstrated effective blinding for both participants and researchers, indicating that the sham stimulation was convincing, which supports the use of higher amplitudes for potentially greater therapeutic effects in older adults.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tolerability and blinding of high-definition transcranial direct current stimulation among older adults at intensities of up to 4 mA per electrode. El Jamal, C., Harrie, A., Rahman-Filipiak, A., 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]

In a study involving 10 patients with Alzheimer's disease, anodal transcranial direct current stimulation (AtDCS) significantly improved recognition memory performance, while cathodal tDCS (CtDCS) led to a decline in performance.

tDCS is shown to be a safe and inexpensive method that could enhance cognitive function in Alzheimer's patients, suggesting potential for further research on its use alongside other treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial direct current stimulation improves recognition memory in Alzheimer disease. Ferrucci, R., Mameli, F., Guidi, I., et al.[2022]

Transcranial electrical stimulation (tES) methods, including tDCS, tACS, tRNS, and tPCS, were effective in reversing cognitive impairments caused by beta-amyloid in a rat model of Alzheimer's disease, indicating potential therapeutic benefits.

Among the different stimulation paradigms, tRNS showed the most significant improvement in memory performance, suggesting that various tES techniques could be viable options for treating cognitive deficits in Alzheimer's patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ameliorative Effects of Different Transcranial Electrical Stimulation Paradigms on the Novel Object Recognition Task in a Rat Model of Alzheimer Disease. Zarifkar, AH., Zarifkar, A., Nami, M., et al.[2022]

Transcranial direct current stimulation (tDCS) significantly improved cognitive function in patients with mild to moderate Alzheimer's disease, based on a meta-analysis of seven studies involving 146 patients, with a standardized mean difference of 0.37.

Single sessions of tDCS were effective, particularly when stimulating the temporal cortex, while repeated sessions and lower current densities did not show significant benefits, highlighting the need for careful consideration of treatment parameters.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial Direct Current Stimulation Improves Cognitive Function in Mild to Moderate Alzheimer Disease: A Meta-Analysis. Cai, M., Guo, Z., Xing, G., et al.[2020]

A novel treatment combining rTMS and tDCS (rTMS-tDCS) significantly improved neuropsychiatric symptoms in Alzheimer's disease patients compared to single-tDCS and sham treatments, with benefits observed at both 4 and 12 weeks after treatment.

The rTMS-tDCS technique also enhanced cognitive function and sleep quality, demonstrating its efficacy and safety, as adverse events were minimal and short-lived.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of simultaneous rTMS-tDCS over bilateral angular gyrus on neuropsychiatric symptoms in patients with moderate Alzheimer's disease: A prospective, randomized, sham-controlled pilot study. Hu, Y., Jia, Y., Sun, Y., et al.[2023]

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 patient with early-onset Alzheimer's disease showed significant improvements in immediate recall (39%) and delayed recall (23%) after daily transcranial direct current stimulation (tDCS) for 8 months, indicating potential cognitive benefits.

The results suggest that tDCS may help stabilize cognitive functions and possibly slow cognitive decline in Alzheimer's disease, warranting further investigation in clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Can 8 months of daily tDCS application slow the cognitive decline in Alzheimer's disease? A case study. Bystad, M., Rasmussen, ID., Grønli, O., et al.[2018]

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