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?

In this research study we want to learn more about the effects of non-invasive brain stimulation on memory and brain-network function in cognitively unimpaired older adults and in patients with amnestic mild cognitive impairment (aMCI). This study will use a form of non-invasive brain stimulation called repetitive Transcranial Magnetic Stimulation (rTMS). rTMS will slightly alter activity in an area of your brain that controls memory. Changes resulting from this stimulation will be measured with behavioral tests of memory and general cognition, as well as by taking images of your brain with Magnetic Resonance Imaging (MRI). Participants will come in for one baseline visit followed by 10 days of daily rTMS study visits (Monday through Friday) and an evaluation visit. Then, there will be a 2-week break. After this break, they will return for another baseline visit, an additional 10 days of rTMS, and a final evaluation visit.

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 safety data exists for Transcranial Magnetic Stimulation in Alzheimer's treatment?

Safety data for Transcranial Magnetic Stimulation (TMS), including repetitive TMS (rTMS), has been developed over decades. Initial safety guidelines were published in 1996, with updates in 2008 and 2021. These guidelines cover potential adverse events, precautions, and dosing considerations. While rTMS is generally considered safe, side effects such as seizures, cognitive changes, and other adverse effects have been observed. Specific studies on Alzheimer's patients suggest rTMS can reduce symptoms with few reported adverse reactions, but comprehensive safety data is still limited. ^{1 2 3 4 5}

Is repetitive transcranial magnetic stimulation (rTMS) safe for humans?

Repetitive transcranial magnetic stimulation (rTMS) has been used safely in both healthy individuals and those with various brain-related conditions since the 1990s, with safety guidelines updated as recently as 2021. While some side effects like seizures and cognitive changes have been noted, these are generally rare, and the treatment is considered noninvasive and safe when proper guidelines are followed. ^{1 2 3 4 5}

Is Transcranial Magnetic Stimulation a promising treatment for Alzheimer's Disease?

Yes, Transcranial Magnetic Stimulation (rTMS) shows promise as a treatment for Alzheimer's Disease. Studies suggest it may help improve cognitive function, which is the ability to think and remember, in people with Alzheimer's. ^{3 6 7 8 9}

How is the treatment repetitive transcranial magnetic stimulation (rTMS) different from other treatments for Alzheimer's disease?

Repetitive transcranial magnetic stimulation (rTMS) is unique because it uses magnetic fields to stimulate nerve cells in the brain, potentially improving cognitive function in Alzheimer's patients. Unlike traditional medications, rTMS is a non-invasive procedure that targets specific brain areas, and it may offer temporary cognitive benefits, although its long-term effectiveness is still being studied. ^{3 6 7 8 9}

What data supports the idea that Transcranial Magnetic Stimulation for Alzheimer's Disease is an effective treatment?

The available research shows that Transcranial Magnetic Stimulation (rTMS) might help improve cognitive function in people with Alzheimer's disease. One study found that patients who received real rTMS treatment showed a trend toward improved cognitive scores compared to those who received a fake treatment. However, these improvements were temporary and disappeared two months after the treatment ended. While some studies suggest potential benefits, the overall results are mixed, and more research is needed to confirm its effectiveness. ^{3 6 7 8 9}

What data supports the effectiveness of the treatment Transcranial Magnetic Stimulation for Alzheimer's Disease?

Research suggests that repetitive transcranial magnetic stimulation (rTMS) might help improve cognitive function in people with Alzheimer's disease, although the results are not definitive. Some studies show a trend toward improved cognitive scores, but the effects may be temporary. ^{3 6 7 8 9}

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

I do not have any serious illnesses that would prevent me from following the study rules.

Another major neurologic or psychiatric condition

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 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]

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 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]

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) 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]

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]

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]

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]

Citations

1. United States 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. [2014]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Repetitive Transcranial Magnetic Stimulation as an Alternative Therapy for Cognitive Impairment in Alzheimer's Disease: A Meta-Analysis. [2015]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Repetitive Transcranial Magnetic Stimulation as a Treatment for Veterans with Cognitive Impairment and Multiple Comorbidities. [2023]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Repetitive Transcranial Magnetic Stimulation With H-Coil in Alzheimer's Disease: A Double-Blind, Placebo-Controlled Pilot Study. [2021]

5. United States 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. [2019]

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

Safety Review for Clinical Application of Repetitive Transcranial Magnetic Stimulation. [2023]

7. England 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. [2023]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Randomized, sham-controlled, clinical trial of repetitive transcranial magnetic stimulation for patients with Alzheimer's dementia in Japan. [2023]

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

Side effects of repetitive transcranial magnetic stimulation. [2005]