RTMS for Dementia

(rTMS for demen Trial)

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: VA Office of Research and Development

Must not be taking: Seizure-inducing drugs

Disqualifiers: Seizure disorder, Psychosis, Substance abuse, others

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

Compensation: Varies

Number of Visits: 10

Duration: 8 weeks

32 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose is to is to study if repetitive transcranial magnetic stimulation (rTMS) improves cognitive function in patients with neurodegenerative conditions which may manifest as mild to moderate cognitive impairment and, in late phase, dementia. This study also intends to investigate if the responses to rTMS intervention are either positively or negatively correlated with the initial severity of cognitive impairment.

Will I have to stop taking my current medications?

The trial requires that if you are on a medication for cognition, your dose must be stable for at least 4 weeks before starting and remain stable during the treatment phase. You may need to stop medications that increase the risk of seizures at least two weeks before treatment.

What data supports the effectiveness of the treatment RTMS for dementia?

Research shows that repetitive transcranial magnetic stimulation (rTMS) has beneficial effects on Alzheimer's disease, improving cognitive functions when used alone or with other treatments. It is a safe, non-invasive method that has shown promise in early intervention and as an add-on to standard care. ^{1 2 3 4 5}

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

Repetitive transcranial magnetic stimulation (rTMS) is generally considered safe when used according to guidelines, with common side effects being minor, such as headaches. There is a low risk of more serious events like seizures, but these are rare and associated with specific risk factors that can be screened for before treatment. ^{6 7 8 9 10}

How does the treatment RTMS differ from other treatments for dementia?

Repetitive transcranial magnetic stimulation (rTMS) is unique because it is a non-invasive treatment that uses magnetic fields to stimulate specific areas of the brain, potentially improving cognitive functions in dementia patients. Unlike traditional medications, rTMS targets brain activity directly and can be used alongside standard treatments to enhance their effects. ^{1 2 4 11 12}

Research Team

Jauhtai J Cheng, MD

Principal Investigator

VA Palo Alto Health Care System, Palo Alto, CA

Eligibility Criteria

This trial is for veterans aged 55 or older with mild to moderate cognitive impairment or dementia likely due to Alzheimer's, who can attend clinic visits and have stable medication doses. They must be able to consent and not have pacemakers, cochlear implants, metal in the brain, seizure risks, severe hearing issues, active CNS diseases increasing seizure risk, recent traumatic brain injury or current psychosis.

Inclusion Criteria

Ability to obtain a Motor Threshold, determined during the screening process

I can read and understand the consent form and agree to participate in the study.

I am a veteran aged 55 or older with Mild Cognitive Impairment or Alzheimer's.

Exclusion Criteria

Have an implanted device deep brain stimulation or metal in the brain

Active current suicidal intent or plan as determined by patient report or chart review

Traumatic brain injury within the last two months

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive repetitive transcranial magnetic stimulation (rTMS) applied to the dorsolateral prefrontal cortex

8 weeks

8 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including cognitive assessments and biomarker analysis

4 months

2 visits (in-person)

Treatment Details

Interventions

• RTMS
• sham

Trial Overview The study tests whether repetitive transcranial magnetic stimulation (rTMS) improves cognitive function in patients with neurodegenerative conditions leading to dementia. It also examines if the severity of initial cognitive impairment affects rTMS response. Participants are randomly assigned to receive either rTMS or a sham (placebo-like) procedure.

Participant Groups

Group I: RTMS Experimental Treatment 1 Intervention

repetitive transcranial magnetic stimulation

Group II: sham Placebo Group 1 Intervention

sham noise to block the sound of treatment

Who Is Running the Clinical Trial?

VA Office of Research and Development

Lead Sponsor

Trials

1,691

Recruited

3,759,000+

Findings from Research

In a study involving 19 participants, both a simple rTMS protocol targeting the left dorsolateral prefrontal cortex (lDLPFC) and a complex protocol involving six brain regions showed similar improvements in cognitive function, behavior, and functionality after 3 weeks of treatment.

The benefits of rTMS were maintained for an additional 4 weeks without further treatment, suggesting that targeting the lDLPFC alone may be sufficient for clinical improvement in Alzheimer's disease symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Similar clinical improvement and maintenance after rTMS at 5 Hz using a simple vs. complex protocol in Alzheimer's disease. Alcalá-Lozano, R., Morelos-Santana, E., Cortés-Sotres, JF., et al.[2022]

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 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]

Repetitive transcranial magnetic stimulation (rTMS) is generally safe for older adults with late-life depression, with only 12.4% reporting any adverse events and serious adverse events occurring in just 1.5% of cases, based on a review of 11 studies involving 353 patients.

The most common adverse events were mild, such as headaches (6.9%) and discomfort at the stimulation site (2.7%), although some serious adverse events, including psychiatric hospitalization and increased suicidal ideation, were noted in case reports, highlighting the need for further research to ensure safety in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse events of repetitive transcranial magnetic stimulation in older adults with depression, a systematic review of the literature. Overvliet, GM., Jansen, RAC., van Balkom, AJLM., et al.[2021]

A patient with treatment-resistant depression (TRD) showed unexpected improvement after experiencing a seizure during repetitive transcranial magnetic stimulation (rTMS), suggesting a potential link between seizure activity and therapeutic effects in TRD.

While rTMS is generally safe, known adverse events include headaches and seizures; this case highlights an unusual outcome where a seizure may have contributed to the patient's improvement, warranting further investigation into the mechanisms of rTMS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment-Resistant Depression Entering Remission Following a Seizure during the Course of Repetitive Transcranial Magnetic Stimulation. Kim, JW., Bae, KY., Kim, SW., et al.[2020]

Repetitive Transcranial Magnetic Stimulation (rTMS) has a good overall safety profile for treating depression, with common side effects like headaches being minor and manageable.

While there is a low incidence of serious side effects such as seizures and hypomania, these are linked to specific risk factors, suggesting that proper screening can enhance patient safety during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A review of the safety of repetitive transcranial magnetic stimulation as a clinical treatment for depression. Loo, CK., McFarquhar, TF., Mitchell, PB.[2021]

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]

References

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

Similar clinical improvement and maintenance after rTMS at 5 Hz using a simple vs. complex protocol in Alzheimer's disease. [2022]

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

Repetitive Transcranial Magnetic Stimulation in the Treatment of Alzheimer's Disease and Other Dementias. [2021]

3. Germany pubmed.ncbi.nlm.nih.gov

Repetitive transcranial magnetic stimulation for cognitive impairment in Alzheimer's disease: a meta-analysis of randomized controlled trials. [2021]

4. 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]

5. England pubmed.ncbi.nlm.nih.gov

Early intervention attenuates synaptic plasticity impairment and neuroinflammation in 5xFAD mice. [2021]

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. England pubmed.ncbi.nlm.nih.gov

Adverse events of repetitive transcranial magnetic stimulation in older adults with depression, a systematic review of the literature. [2021]

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

Treatment-Resistant Depression Entering Remission Following a Seizure during the Course of Repetitive Transcranial Magnetic Stimulation. [2020]

10. England pubmed.ncbi.nlm.nih.gov

A review of the safety of repetitive transcranial magnetic stimulation as a clinical treatment for depression. [2021]

11. Netherlands pubmed.ncbi.nlm.nih.gov

Diagnostic contribution and therapeutic perspectives of transcranial magnetic stimulation in dementia. [2021]

12. 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]