tDCS for Alzheimer's Disease

(NICE-AD Trial)

Not currently recruiting at 1 trial location

Overseen By Mirnova Ceide, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Albert Einstein College of Medicine

Must not be taking: Monoclonal antibodies

Disqualifiers: Unstable medical, psychiatric illnesses, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 6 months

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 Alzheimer's Disease (AD) manage symptoms at home. It uses a device called tDCS (Transcranial Direct Current Stimulation), which sends a mild electrical current to a part of the brain to potentially improve memory and thinking skills. Researchers aim to determine if using this device five times a week for six months can make a difference. People with mild to moderate Alzheimer's, who live at home and maintain a stable medication routine, may be suitable for this study. As an unphased trial, this study offers participants the chance to contribute to innovative research that could enhance at-home care for Alzheimer's patients.

Will I have to stop taking my current medications?

The trial does not require you to stop taking your current dementia medications, but your medication regimen should be stable for at least 4 weeks before joining. Your doctor can still adjust your medications during the trial if needed.

What prior data suggests that this tDCS device is safe for Alzheimer's patients?

Research has shown that transcranial Direct Current Stimulation (tDCS) is generally safe for people with Alzheimer's Disease (AD). In studies involving over a thousand adults, participants tolerated the treatment well. Most experienced only mild side effects, such as slight tingling on the scalp. No major or serious negative effects were reported. This suggests that tDCS is a low-risk option for managing AD symptoms. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about using transcranial direct current stimulation (tDCS) for Alzheimer's disease because it offers a non-invasive way to potentially enhance brain function. Unlike traditional medications that aim to manage symptoms through chemical means, tDCS uses a gentle electrical current to stimulate specific areas of the brain, which might improve memory and cognitive abilities. This method stands out because it sidesteps the side effects commonly associated with drugs, offering a novel approach that could complement existing treatments like cholinesterase inhibitors and memantine.

What evidence suggests that this tDCS device is effective for Alzheimer's Disease?

Research has shown that transcranial Direct Current Stimulation (tDCS) can enhance thinking and memory in individuals with Alzheimer's Disease (AD). A review of several studies found that tDCS boosts overall brain function in those with mild cognitive impairment (MCI) and AD. Notably, individuals with AD experienced greater improvement than those with MCI or other types of dementia. One study suggested that using tDCS twice daily could further benefit brain function in AD patients. In this trial, participants will receive either active tDCS or sham tDCS to evaluate its effectiveness in managing AD symptoms. ^{2 4 6 7 8}

Who Is on the Research Team?

Joe Verghese, MD

Principal Investigator

Stony Brook University

Lara Dhingra, PhD

Principal Investigator

Metropolitan Jewish Health System

Mirnova Ceide, MD

Principal Investigator

Albert Einstein College of Medicine

Are You a Good Fit for This Trial?

This trial is for people aged 60 or older with mild to moderate Alzheimer's Disease, diagnosed by specialists. Participants must be stable on dementia medications if any, speak English or Spanish well enough for study procedures, and agree to an MRI scan. Those with unstable health conditions, skin issues where electrodes are placed, head trauma history, metal implants in the head/neck, or involved in other studies can't join.

Inclusion Criteria

I am willing to undergo an MRI scan.

I can speak and understand English or Spanish well enough for medical procedures.

My dementia is in the mild to moderate stage.

Exclusion Criteria

Exclusions specific to neuroimaging procedure: surgically implanted metallic devices such as aneurysm clips or pacemakers, large amounts of dental or surgical hardware in the head and neck, known history of claustrophobia, weight >350lbs, or waist circumference >55 inches

I have a history of head trauma, seizures, brain surgery, stroke, or cancer affecting my head.

I have skin issues where electrodes might be placed.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive remotely supervised active tDCS or sham tDCS stimulation over the dorsolateral prefrontal cortex for 30 minutes, 5 times per week for 6 months at home

6 months

Follow-up

Participants are monitored for durability of tDCS effects on cognitive performance and neuroplasticity

3 months

What Are the Treatments Tested in This Trial?

Interventions

• tDCS device model Soterix mini-CT (Soterix Medical Inc., New York, NY) programed to deliver active tDCS
• tDCS device model Soterix mini-CT (Soterix Medical Inc., New York, NY) programed to deliver sham tDCS

Trial Overview The study tests a tDCS device delivering either active or sham (fake) stimulation to the brain's dorsolateral prefrontal cortex at home. It aims to see if this treatment improves cognitive performance and symptoms over six months and affects neuroplasticity markers in patients with Alzheimer's.

How Is the Trial Designed?

Group I: Active tDCS Experimental Treatment 1 Intervention

The active tDCS will involve 30-minutes of direct current at intensity of 2 milliamperes (mA).

Group II: Sham tDCS Placebo Group 1 Intervention

Sham stimulation consists of the direct current ramped up to 2mA over 30 seconds, ramped down over 30 seconds and stay at 0 current for the remaining application period.

tDCS device model Soterix mini-CT (Soterix Medical Inc., New York, NY) programed to deliver active tDCS is already approved in United States, European Union for the following indications:

Approved in United States as tDCS for:

• Investigational use for cognitive enhancement in Alzheimer's disease

Approved in European Union as tDCS for:

• Investigational use for cognitive enhancement in Alzheimer's disease

Who Is Running the Clinical Trial?

Albert Einstein College of Medicine

Lead Sponsor

Trials

302

Recruited

11,690,000+

Stony Brook University

Collaborator

Trials

225

Recruited

41,700+

National Institute on Aging (NIA)

Collaborator

Trials

1,841

Recruited

28,150,000+

MJHS Institute for Innovation in Palliative Care

Collaborator

Trials

6

Recruited

1,700+

Published Research Related to This Trial

Transcranial direct current stimulation (tDCS) is a non-invasive method that uses controlled electrical currents through electrodes on the scalp to modulate brain function, with device design being crucial for effectiveness and user comfort.

High-definition tDCS, which employs smaller electrodes in specific arrangements, can enhance the precision of brain stimulation, and while safety is generally protocol-specific, using medical-grade devices helps minimize risks associated with tDCS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Physics of Transcranial Direct Current Stimulation Devices and Their History. Truong, DQ., Bikson, M.[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]

In a clinical trial involving 16 participants with moderate-to-severe major depression, transcranial direct current stimulation (tDCS) led to a significant reduction in depressive symptoms within just two weeks of treatment, as measured by the Montgomery-Åsberg Depression Rating Scale.

By the end of the treatment and tapering phase, 75% of participants responded positively to the tDCS intervention, with 63% achieving remission, indicating that tDCS can be an effective option for managing major depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Home-administered transcranial direct current stimulation is a feasible intervention for depression: an observational cohort study. Charvet, L., George, A., Charlson, E., et al.[2023]

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]

A study involving 24 rats showed that 500 μA cathodal transcranial direct current stimulation (tDCS) applied for 10 days was safe, with no adverse effects on motor functions, learning, or memory.

The treatment did not cause any significant changes in brain morphology, neurotransmitter levels, or overall organ health, indicating that this level of tDCS is safe for use in research settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A safety study of 500 μA cathodal transcranial direct current stimulation in rat. Zhang, K., Guo, L., Zhang, J., et al.[2020]

In a study involving 50 participants, the effects of different tDCS devices and electrode sizes on quadriceps motor cortical excitability were evaluated, and no significant differences were found, suggesting that these factors do not impact the effectiveness of tDCS.

The results indicated that anodal tDCS did not significantly alter motor cortical excitability, leading to the conclusion that future research should focus on whether behavioral outcomes vary with different tDCS devices or electrode sizes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of conventional transcranial direct current stimulation devices and electrode sizes on motor cortical excitability of the quadriceps muscle. Gardi, AZ., Vogel, AK., Dharia, AK., et al.[2022]

Optimized high-definition montages for transcranial direct current stimulation (tDCS) can increase stimulation intensity by an average of 0.3 V/m compared to unoptimized montages, which is crucial for targeting areas beneath skull defects.

Large skull defects with titanium or acrylic plates can reduce stimulation intensity by about 80%, while smaller defects filled with cerebrospinal fluid or scar tissue can increase stimulation intensity by about 200%, highlighting the importance of individual anatomical considerations in tDCS treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimized high-definition tDCS in patients with skull defects and skull plates. Guillen, A., Truong, DQ., Datta, A., et al.[2023]

A review of 15 studies on transcranial direct current stimulation (tDCS) before 1998 found that most trials (about 83%) focused on treating psychiatric conditions like depression and schizophrenia, with 12 out of 15 studies showing positive outcomes.

While the stimulation intensities used in older studies were lower than modern standards, the longer session durations and higher current densities suggest that these factors may have contributed to the encouraging results and mild side effects reported, such as headaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Notes on Human Trials of Transcranial Direct Current Stimulation between 1960 and 1998. Esmaeilpour, Z., Schestatsky, P., Bikson, M., 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]

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 a safe and well-tolerated technique, with no serious adverse effects reported in a study involving 131 healthy subjects across 277 sessions.

While sensory side effects like tingling and itching are common, they are generally mild; however, the higher occurrence and severity of these side effects during active stimulation compared to sham stimulation suggest that the current sham method may not be an effective control in some research contexts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Differences in the experience of active and sham transcranial direct current stimulation. Kessler, SK., Turkeltaub, PE., Benson, JG., et al.[2021]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39089145/

Systematic review and meta-analysis of transcranial direct ... Conclusion: The tDCS can ameliorate the global cognition of patients with MCI and AD, and it has a better rehabilitation effect than non-tDCS or sham-tDCS.

2. alzres.biomedcentral.com alzres.biomedcentral.com/articles/10.1186/s13195-025-01677-y

A systematic review and meta-analysis of the impact of ... People with AD showed greater improvements compared to those with MCI or dementia (SMD = 0.91, p = 0.02). However, tDCS did not significantly ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S2274580724006150

High definition transcranial direct current stimulation as an ... In this pilot trial, no statistically significant differences on cognitive outcomes were found between sham and active HD-tDCS immediately post-treatment (p's > ...

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

Impact of twice-a-day transcranial direct current stimulation ... Conclusions Our research indicates for the first time that twice-a-day tDCS may improve the cognitive function of patients with AD. This study ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11900501/

Efficacy of Transcranial Direct Current Stimulation and ... Efficacy of transcranial direct current stimulation and photobiomodulation in improving cognitive abilities for Alzheimer's disease: a systematic review.

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

Safety and feasibility of optimized transcranial direct current ... This study aims to determine the feasibility and safety of applying tDCS treatment using optimized and personalized tDCS electrode positions in patients with ...

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0197457224001927

Systematic review and meta-analysis of transcranial ... We conducted a meta-analysis of twenty-two trials involving 1074 adults with mild cognitive impairment and Alzheimer's disease.

8. mdpi.com mdpi.com/2077-0383/14/5/1766

Efficacy of Transcranial Direct Current Stimulation and ... We assessed the efficacy and safety of tDCS and PBM and their potential to enhance cognitive functions in individuals with AD.