Transcranial Magnetic Stimulation for Alzheimer's Disease

Overseen By Alexandra Touroutoglou, PhD

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Massachusetts General Hospital

Must not be taking: Epileptogenic, Anti-amyloid

Disqualifiers: Head trauma, Neurologic condition, Seizures, others

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 12

Duration: 2 weeks

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how repetitive Transcranial Magnetic Stimulation (rTMS) affects memory and brain function, particularly in individuals with mild memory issues or at risk for Alzheimer's. rTMS is a non-invasive method that uses magnetic fields to gently alter brain activity related to memory. Participants will take memory tests and undergo brain scans to assess the effects. The trial suits native English speakers aged 40 to 99 who have mild memory problems or are at risk for Alzheimer's. As an Early Phase 1 trial, this research aims to understand how rTMS works in people, offering participants a chance to contribute to groundbreaking science.

Do I need to stop my current medications to join the trial?

The trial does not specify if you need to stop all current medications, but you cannot take medications that are highly epileptogenic or be on anti-amyloid treatments.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications that are highly epileptogenic (likely to cause seizures), such as clozapine, high doses of bupropion, and others listed in the exclusion criteria. If you are on anti-amyloid treatments, you will also need to stop those to participate.

What prior data suggests that this technique is safe for use in humans?

Research has shown that repetitive Transcranial Magnetic Stimulation (rTMS) is generally safe. Serious side effects are rare in studies. Most side effects, such as mild headaches or slight discomfort at the stimulation site, are minor and temporary.

Some studies have explored rTMS for Alzheimer's and similar conditions, finding no harm to participants. Although the quality of evidence varies, no serious safety concerns have been reported. Importantly, rTMS is already approved for treating depression, indicating its safety for brain-related conditions.

In this trial, all participants will receive the same rTMS treatment. The study is in its early stages, so fewer people have tried the treatment so far. However, existing evidence suggests rTMS is safe for testing in humans. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Transcranial Magnetic Stimulation (TMS) is unique because it offers a non-invasive way to potentially treat Alzheimer's disease by directly stimulating specific brain regions with magnetic fields. Unlike traditional treatments that primarily focus on managing symptoms with medications, TMS aims to alter brain activity patterns, potentially addressing the underlying neural dysfunctions of the disease. Researchers are excited about TMS because it could provide a new approach to slowing cognitive decline, offering hope for those with Alzheimer's disease where existing treatments have limited effectiveness.

What evidence suggests that repetitive Transcranial Magnetic Stimulation is effective for Alzheimer's Disease?

Research has shown that repetitive Transcranial Magnetic Stimulation (rTMS) might enhance memory and thinking skills in people with Alzheimer's. For instance, studies have found that rTMS can improve scores on cognitive ability tests in Alzheimer's patients. Additionally, animal studies have demonstrated that rTMS can prevent memory decline, suggesting potential benefits for humans. Early findings indicate that this non-invasive treatment might help maintain brain function by slightly altering brain activity related to memory. Although more research is needed, these initial results offer promise for those with mild cognitive impairment. Participants in this trial will receive rTMS as part of the study interventions. ^{1 2 6 7 8}

Are You a Good Fit for This Trial?

This trial is for older adults with good general health who have Alzheimer's, various types of cognitive impairments, or memory issues. They should be able to undergo MRI scans and attend multiple study visits over several weeks. People with metal implants in their head, seizure history, or severe psychiatric conditions cannot participate.

Inclusion Criteria

Patients with PPA will be asked to bring a study partner to all visits

I am a native English speaker.

Willing and able to consent to the protocol and undergo imaging and neuropsychological testing at the specified time points

Exclusion Criteria

Another major neurologic or psychiatric condition

Unwilling to return for follow-up, undergo neuropsychological testing, TMS, and MR imaging

I have had a head injury that made me lose or alter my consciousness.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline

Participants undergo baseline assessments including behavioral tests of memory and brain imaging

1 day

1 visit (in-person)

Treatment

Participants receive daily rTMS for 10 days, followed by an evaluation visit

2 weeks

10 visits (in-person) for rTMS, 1 evaluation visit (in-person)

Break

Participants have a 2-week break with no treatment

2 weeks

Second Treatment

Participants undergo another baseline visit, followed by 10 days of rTMS and a final evaluation visit

2 weeks

1 baseline visit (in-person), 10 visits (in-person) for rTMS, 1 final evaluation visit (in-person)

Follow-up

Participants are monitored for changes in brain network connectivity and memory post-treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Transcranial Magnetic Stimulation

Trial Overview

The study tests repetitive Transcranial Magnetic Stimulation (rTMS), a non-invasive brain stimulation technique aimed at improving memory and brain function. Participants will receive rTMS daily on weekdays for two separate 10-day periods with a break in between.

How Is the Trial Designed?

Group I: AD, aMCI, lvPPA patients, and preclinical AD Experimental Treatment 2 Interventions

All participants will receive the same study interventions in a within-subject crossover design.

Transcranial Magnetic Stimulation is already approved in United States, Canada, European Union for the following indications:

Approved in United States as Transcranial Magnetic Stimulation for:

• Major Depressive Disorder
• Obsessive Compulsive Disorder

Approved in Canada as Transcranial Magnetic Stimulation for:

• Major Depressive Disorder

Approved in European Union as Transcranial Magnetic Stimulation for:

• Major Depressive Disorder

Who Is Running the Clinical Trial?

Massachusetts General Hospital

Lead Sponsor

Trials

3,066

Recruited

13,430,000+

Published Research Related to This Trial

In a study involving 42 Japanese patients with Alzheimer's dementia, 4 weeks of repetitive transcranial magnetic stimulation (rTMS) at 120% resting motor threshold showed significant efficacy in improving cognitive function for patients with MMSE scores ≥ 15, with 41.7% of participants experiencing a notable improvement compared to 0% in the Sham group.

The treatment was found to be safe, with no serious adverse events reported, suggesting that rTMS could be a promising intervention for patients with moderate to mild Alzheimer's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized, sham-controlled, clinical trial of repetitive transcranial magnetic stimulation for patients with Alzheimer's dementia in Japan. Saitoh, Y., Hosomi, K., Mano, T., et al.[2023]

In a study involving 12 Alzheimer's disease patients, four sessions of high-frequency repetitive transcranial magnetic stimulation (rTMS) over two weeks led to significant improvements in language skills, which were sustained for at least four weeks after treatment.

Functional MRI results indicated increased brain activation during cognitive tasks following rTMS, supporting the idea that rTMS may enhance cognitive function in Alzheimer's patients, consistent with findings from other studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Open-label, short-term, repetitive transcranial magnetic stimulation in patients with Alzheimer's disease with functional imaging correlates and literature review. Devi, G., Voss, HU., Levine, D., et al.[2014]

Repetitive transcranial magnetic stimulation (rTMS) showed significant cognitive improvement in Alzheimer's disease patients compared to sham stimulation, as indicated by a reduction in ADAS-cog scores, but did not show improvement in MMSE scores.

rTMS was well tolerated with only a few mild adverse events reported, suggesting it is a safe intervention with potential benefits for cognitive function in Alzheimer's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repetitive transcranial magnetic stimulation for the treatment of Alzheimer's disease: A systematic review and meta-analysis of randomized controlled trials. Dong, X., Yan, L., Huang, L., et al.[2019]

Repetitive transcranial magnetic stimulation (rTMS) has gained popularity for its ability to modulate brain activity, but safety considerations are crucial, especially with the recent updates to safety guidelines published in 2021.

The guidelines emphasize the importance of screening for risks, monitoring for adverse events, and specific safety measures when using rTMS, particularly in patients with conditions like stroke and traumatic brain injury.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety Review for Clinical Application of Repetitive Transcranial Magnetic Stimulation. Kim, WS., Paik, NJ.[2023]

In a pilot study involving 26 Veterans, 20 sessions of repetitive transcranial magnetic stimulation (rTMS) over 4 weeks were well-tolerated and showed improved auditory-verbal memory compared to a sham treatment, indicating potential cognitive benefits for Alzheimer's disease.

While rTMS improved memory, there was a concerning trend of decreased semantic verbal fluency in the active treatment group, suggesting that further research is needed to confirm these findings and assess the overall cognitive impact.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repetitive Transcranial Magnetic Stimulation as a Treatment for Veterans with Cognitive Impairment and Multiple Comorbidities. Cheng, J., Fairchild, JK., McNerney, MW., et al.[2023]

Repetitive transcranial magnetic stimulation (rTMS) has not been thoroughly studied for side effects, with the main known risk being the acute production of seizures.

While tissue damage from rTMS is unlikely, there are concerns about potential cognitive effects and the possibility of long-term changes in brain function that have not yet been fully understood.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Side effects of repetitive transcranial magnetic stimulation. Wassermann, EM.[2005]

This meta-analysis of seven studies involving 94 patients with mild to moderate Alzheimer's disease found that high-frequency repetitive transcranial magnetic stimulation (rTMS) significantly improves cognitive function, with a standardized mean difference of 1.00, indicating a strong effect.

The effectiveness of rTMS was found to be dependent on the stimulation frequency and the targeted brain hemisphere, with significant improvements observed when stimulating the right or bilateral dorsolateral prefrontal cortex, but not the left.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repetitive Transcranial Magnetic Stimulation as an Alternative Therapy for Cognitive Impairment in Alzheimer's Disease: A Meta-Analysis. Liao, X., Li, G., Wang, A., et al.[2015]

In a pilot study involving 30 Alzheimer's disease patients, focal repetitive transcranial magnetic stimulation (rTMS) using the H2-coil showed a trend toward improved cognitive function, with a mean decrease of -1.01 points on the ADAS-Cog scale after treatment, although this effect was not sustained two months post-treatment.

The study indicates that rTMS with the H2-coil is safe and feasible for Alzheimer's patients, suggesting potential cognitive benefits that warrant further investigation in larger trials, especially when combined with cognitive rehabilitation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repetitive Transcranial Magnetic Stimulation With H-Coil in Alzheimer's Disease: A Double-Blind, Placebo-Controlled Pilot Study. Leocani, L., Dalla Costa, G., Coppi, E., et al.[2021]

Repetitive transcranial magnetic stimulation (rTMS) can effectively improve cognitive function and behavioral symptoms in dementia patients, as demonstrated in a case where a patient showed significant improvement after switching from 1 Hz to 10 Hz rTMS.

While rTMS is generally beneficial, it can lead to adverse reactions such as seizures; however, adjusting the treatment parameters (like reducing the frequency) can help mitigate these risks and continue to improve patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The repetitive transcranial magnetic stimulation in Alzheimer's disease patients with behavioral and psychological symptoms of dementia: a case report. Yang, Z., Zhou, Y.[2023]

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