tDCS for Alzheimer's Disease

(NICE-AD Trial)

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

100 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

The prevalence of Alzheimer's Disease (AD) is rising, but existing medications provide only modest control of cognitive decline and associated symptoms, and novel therapies are urgently needed. This randomized sham-controlled trial will determine if an innovative low-risk remotely-supervised transcranial Direct Current Stimulation (tDCS) applied over the area of the dorsolateral prefrontal cortex for 30 minutes at the intensity of 2 mA five times per week for 6 months at home can improve cognitive performance and symptoms and modulate neuroimaging markers of neuroplasticity in 100 patients with mild to moderate AD. If effective, this novel intervention can substantially enhance AD symptom management at home, improve quality of life of AD patients and their families, and reduce burden associated with this debilitating illness.

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.

Is transcranial direct current stimulation (tDCS) generally safe for humans?

Research shows that transcranial direct current stimulation (tDCS) is generally safe for humans when used in conventional protocols, with no reports of serious adverse effects in over 33,200 sessions. However, some studies caution that tDCS could potentially be harmful, so it's important to follow medical guidance and use approved devices. ^{1 2 3 4 5}

How does tDCS treatment for Alzheimer's differ from other treatments?

tDCS (transcranial direct current stimulation) is a unique treatment for Alzheimer's because it is a noninvasive method that uses a small electrical current to stimulate the brain, potentially improving cognitive function. Unlike traditional drug treatments, tDCS can be administered at home and focuses on modulating brain activity rather than altering brain chemistry. ^{2 6 7 8 9}

What data supports the effectiveness of the treatment tDCS for Alzheimer's Disease?

Research shows that transcranial direct current stimulation (tDCS) has been effective in reducing symptoms of depression, with significant improvements noted in patients after several weeks of treatment. This suggests that tDCS may have potential benefits for other brain-related conditions, like Alzheimer's Disease, although direct evidence for Alzheimer's is not provided. ^{2 7 10 11 12}

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.

My medical and mental health conditions are stable.

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+

MJHS Institute for Innovation in Palliative Care

Collaborator

Trials

6

Recruited

1,700+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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) 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]

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]

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]

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]

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]

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]

Citations

1. Netherlands pubmed.ncbi.nlm.nih.gov

Effect of conventional transcranial direct current stimulation devices and electrode sizes on motor cortical excitability of the quadriceps muscle. [2022]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Notes on Human Trials of Transcranial Direct Current Stimulation between 1960 and 1998. [2022]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Home-administered transcranial direct current stimulation is a feasible intervention for depression: an observational cohort study. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Physics of Transcranial Direct Current Stimulation Devices and Their History. [2022]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Optimized high-definition tDCS in patients with skull defects and skull plates. [2023]

6. United States pubmed.ncbi.nlm.nih.gov

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

7. United States pubmed.ncbi.nlm.nih.gov

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

8. United States pubmed.ncbi.nlm.nih.gov

Differences in the experience of active and sham transcranial direct current stimulation. [2021]

9. England pubmed.ncbi.nlm.nih.gov

A safety study of 500 μA cathodal transcranial direct current stimulation in rat. [2020]

10. Korea (South) pubmed.ncbi.nlm.nih.gov

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

11. Netherlands 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. [2020]

12. England pubmed.ncbi.nlm.nih.gov

Neurostimulation for cognitive enhancement in Alzheimer's disease (the NICE-AD study): a randomized clinical trial. [2022]