Brain Stimulation for Alzheimer's Disease

(ISTIM-AD Trial)

Overseen By Kathryn Tasker

Age: 65+

Sex: Any

Trial Phase: Academic

Sponsor: Hebrew SeniorLife

Must not be taking: Antipsychotics, Benzodiazepines, Neuroactive drugs

Disqualifiers: Stroke, Parkinson's, Schizophrenia, 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: 10

Duration: 2 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new brain stimulation technique to determine if it can help individuals with mild Alzheimer's disease improve their thinking and mobility. Researchers will administer ten sessions of a treatment called personalized tDCS (Transcranial Direct Current Stimulation), which sends mild electrical currents to a specific part of the brain. The trial will compare this treatment to a similar procedure that does not affect the brain to assess any real benefits. Participants should be adults with mild Alzheimer's who live in supportive housing and can move around using a cane or walker without assistance. As an unphased trial, this study offers a unique opportunity to contribute to groundbreaking research in Alzheimer's treatment.

Do I have to stop taking my current medications for the trial?

Yes, you must stop taking antipsychotics, anti-seizure medications, benzodiazepines, or other neuroactive medications to participate in the trial.

What prior data suggests that this brain stimulation technique is safe for Alzheimer's patients?

Research shows that transcranial direct current stimulation (tDCS) is generally safe for people. Studies on individuals with Alzheimer's disease have found that multiple tDCS sessions can improve thinking skills without causing major side effects. Personalized tDCS, which adjusts the treatment to each person, has also proven safe.

In the treatment under study, the electrical current remains low, with a maximum of 2.0 milliamperes (mA) per electrode and no more than 4 mA in total. This careful control ensures safety and comfort. Sessions begin and end with a gradual increase and decrease of the current to enhance comfort.

Overall, existing research supports the safety of tDCS, making it a promising option for those considering joining clinical trials for Alzheimer's disease. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about personalized transcranial direct current stimulation (tDCS) for Alzheimer's disease because it offers a tailored approach, potentially enhancing the effectiveness of brain stimulation by customizing the treatment to each individual's brain structure. Unlike current treatments that often involve medications like cholinesterase inhibitors or memantine, which target neurotransmitter systems, personalized tDCS targets the brain's left dorsolateral prefrontal cortex (dlPFC) with a specific electric field to improve cognitive function. This method could lead to more precise and comfortable treatments with fewer side effects, as it fine-tunes the current flow based on the participant's MRI data. Additionally, the active-sham component ensures that any perceived effects are due to the actual treatment, not placebo sensations, offering a robust way to assess the real impact of the therapy.

What evidence suggests that personalized tDCS is effective for Alzheimer's?

Research has shown that personalized transcranial direct current stimulation (tDCS), which participants in this trial may receive, can improve thinking and memory in people with Alzheimer's disease. One study used tDCS to target a specific brain area involved in memory and decision-making. This involved applying a mild electrical current for 20 minutes, which improved overall thinking skills in older adults with mild memory problems due to Alzheimer's. Another study found that conducting tDCS sessions twice a day might boost thinking abilities in people with Alzheimer's. While results can differ, these studies suggest that personalized tDCS could benefit people with mild Alzheimer's disease. This trial will compare personalized tDCS with an active-sham treatment to evaluate its effectiveness further. ^{1 3 6 7 8}

Who Is on the Research Team?

Brad Manor, PhD

Principal Investigator

Hebrew SeniorLife

Are You a Good Fit for This Trial?

This trial is for men and women aged 65 or older with mild Alzheimer's, living in supportive housing. Participants must have some cognitive impairment, difficulty with daily activities, and a specific dementia rating. Excluded are those with MRI or tDCS contraindications like seizures, metal in the body, certain medical devices, skin conditions on the scalp; also excluded are those unable to walk without help (except cane/walker users), severe arthritis/neuropathy sufferers, other neurological condition patients outside of mild AD.

Inclusion Criteria

I am 65 or older and live in a supportive housing facility.

I have mild Alzheimer's with some memory loss and daily activity challenges.

Exclusion Criteria

I have a history of neurological conditions other than mild Alzheimer's Disease.

I need someone's help to walk, but I can use a cane or walker.

I don't have seizures, use certain drugs, have metal in my body, specific implants, or scalp conditions.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a 10-session personalized tDCS intervention targeting the left dorsolateral prefrontal cortex

2 weeks

10 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Personalized tDCS

Trial Overview The study tests a brain stimulation technique called personalized tDCS aimed at improving cognitive function and mobility in Alzheimer's patients. It involves 10 sessions targeting the left prefrontal cortex compared against a sham (placebo-like) procedure to see if there's any benefit.

How Is the Trial Designed?

Group I: Personalized tDCS Experimental Treatment 1 Intervention

Baseline MRIs will enable personalization of tDCS via current flow modeling for optimization to each participant with the goal of generating an average electric field of 0.25 V/m within their identified left dlPFC. The direct current delivered by any one electrode will not exceed 2.0 mA and the total amount of current from all electrodes will not exceed 4 mA. Each 20-minutes session will begin and end with a 60-second ramp up/down of current amplitude to maximize comfort.

Group II: Active-Sham Placebo Group 1 Intervention

The investigators will use an active sham in which very low-level currents (0.5 mA total) will be transferred between electrodes in close proximity on the scalp throughout the entire 20-minute session. This intervention will be optimized to each participant to deliver currents designed to not significantly influence their cortical tissue, but still mimic the cutaneous sensations induced by tDCS.

Personalized tDCS is already approved in United States, European Union for the following indications:

Approved in United States as Transcranial Direct Current Stimulation for:

• Depression
• Cognitive Impairment
• Auditory Hallucinations
• Rehabilitation for Stroke and Neurological Disorders

Approved in European Union as Transcranial Direct Current Stimulation for:

• Depression
• Cognitive Impairment
• Rehabilitation for Stroke and Neurological Disorders

Who Is Running the Clinical Trial?

Hebrew SeniorLife

Lead Sponsor

Trials

52

Recruited

273,000+

Published Research Related to This Trial

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]

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 18 early Alzheimer's disease patients, daily transcranial direct current stimulation (tDCS) over 6 months significantly improved global cognition and language function compared to a sham treatment.

Active tDCS also helped preserve glucose metabolism in specific brain regions, indicating its potential as a therapeutic intervention to stabilize cognitive decline in Alzheimer's patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of 6-month at-home transcranial direct current stimulation on cognition and cerebral glucose metabolism in Alzheimer's disease. Im, JJ., Jeong, H., Bikson, M., 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]

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]

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]

Citations

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

Safety and feasibility of optimized transcranial direct current ... A recent study reported that tDCS over the DLPFC at 2 mA for 20 min in older adults with MCI due to AD effectively improved general cognition ...

2. 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 > ...

3. 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 ...

4. 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.

5. 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.

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38660096/

a multicenter study protocol for a randomized controlled trial 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/pii/S1041610224039474

Effects of Transcranial Direct Current Stimulation (tDCS) on ... Recently, an increasing number of studies have been conducted to evaluate the efficacy of tDCS in AD and concluded a positive therapeutic effect. Currently, ...

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.