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

24 Participants Needed

Trial Summary

What is the purpose of this trial?

The objective of this study is to conduct a pilot, randomized sham-controlled trials to determine the feasibility and effects of a 10-session personalized tDCS intervention targeting the left dorsolateral prefrontal cortex on cognitive function, dual task standing and walking, and other metrics of mobility in 24 older adults with mild AD living in supportive housing.

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 data supports the idea that Brain Stimulation for Alzheimer's Disease (also known as: Personalized tDCS, Transcranial Direct Current Stimulation, tDCS) is an effective treatment?

The available research shows that transcranial direct current stimulation (tDCS) can help improve memory and thinking skills in people with Alzheimer's disease. One study found that tDCS improved recognition memory, which is the ability to remember previously encountered information. Another study highlighted that tDCS could enhance cognitive performance in Alzheimer's patients. Additionally, a long-term study suggested that using tDCS at home for six months could lead to better thinking abilities. These findings suggest that tDCS might be a promising treatment for Alzheimer's disease, offering an alternative to traditional drug therapies. ^{1 2 3 4 5}

What safety data is available for tDCS treatment in Alzheimer's?

Transcranial Direct Current Stimulation (tDCS) is considered safe and well-tolerated, with no reports of serious adverse effects or irreversible injury in human trials. This includes over 33,200 sessions and 1,000 subjects, even among potentially vulnerable populations like the elderly. Safety data from animal studies suggest that brain injury occurs at current densities much higher than those used in conventional tDCS protocols. ^{1 2 3 6 7}

Is Personalized tDCS a promising treatment for Alzheimer's Disease?

Yes, Personalized tDCS is a promising treatment for Alzheimer's Disease. It is a safe and noninvasive method that can help improve memory and cognitive function in patients. Studies show it can slow down or improve the decline in brain function associated with Alzheimer's. ^{1 2 3 4 5}

Research Team

Brad Manor, PhD

Principal Investigator

Hebrew SeniorLife

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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 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) 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) 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]

References

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

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

2. 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]

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

Transcranial direct current stimulation improves recognition memory in Alzheimer disease. [2022]

4. Switzerland 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. [2022]

5. United States 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. [2020]

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

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

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

Transcranial Direct Current Stimulation Improves Cognitive Function in Mild to Moderate Alzheimer Disease: A Meta-Analysis. [2020]