rTMS for Mild Cognitive Impairment

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Maria I. Lapid, M.D.

Disqualifiers: Dementia, Epilepsy, Stroke, Psychosis, others

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

Compensation: Varies

Number of Visits: 21

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if iTBS rTMS, a type of repetitive transcranial magnetic stimulation, can improve memory in individuals with mild cognitive impairment (MCI). Participants will undergo a series of brief, daily sessions where magnetic stimulation targets specific brain areas. The study includes multiple groups, each receiving different sequences of the treatment. Suitable candidates have been diagnosed with MCI, experience memory issues, and do not have dementia. Participants must also speak English fluently and meet specific health and safety standards. As an unphased study, this trial offers participants the chance to contribute to groundbreaking research that could lead to new memory improvement treatments.

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

The trial requires that you have a stable medication regimen for at least 4 weeks before starting. This means you should not change your current medications during that time.

What prior data suggests that this treatment protocol is safe for adults with mild cognitive impairment?

Research shows that intermittent theta burst stimulation (iTBS) repetitive transcranial magnetic stimulation (rTMS) is generally safe. Studies have found that it can enhance thinking skills in individuals with mild cognitive impairment (MCI). Importantly, side effects are rare and usually mild. Some individuals might experience slight tingling, headaches, or discomfort at the treatment site, but these effects typically resolve on their own.

For those considering joining a trial, it is reassuring that iTBS rTMS has been tested in similar studies before. While any treatment carries some risk, evidence so far suggests that iTBS rTMS is safe for most people. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the use of intermittent Theta Burst Stimulation (iTBS) rTMS for Mild Cognitive Impairment because it offers a novel approach compared to traditional treatments like cholinesterase inhibitors or lifestyle interventions. iTBS rTMS is a non-invasive brain stimulation technique that targets specific brain regions, such as the Left Dorsolateral Prefrontal Cortex (DLPFC) and Lateral Parietal Cortex (LPC), which are involved in cognitive processes. This method is distinct because it directly modulates neural activity to potentially enhance cognitive function. Furthermore, iTBS rTMS sessions are brief, lasting only 3.5 minutes, and may offer quicker cognitive improvements, making it an appealing option for those seeking more immediate results.

What evidence suggests that this trial's treatments could be effective for mild cognitive impairment?

Research has shown that intermittent theta burst stimulation (iTBS), a type of repetitive transcranial magnetic stimulation (rTMS), can improve thinking skills in people with mild cognitive impairment (MCI). In this trial, participants will receive iTBS targeting different brain areas. Some participants will receive iTBS on the left dorsolateral prefrontal cortex (DLPFC), which studies have found may enhance memory and attention over time. Others will receive iTBS targeting the lateral parietal cortex (LPC), which similar research suggests might also improve cognitive abilities in MCI, although the specific benefits are still under investigation. These treatments use magnetic pulses to stimulate brain regions involved in thinking, which is believed to enhance brain function. Overall, these early findings are promising and suggest that iTBS could be beneficial for addressing cognitive problems in MCI. ^{1 5 6 7 8}

Who Is on the Research Team?

Maria I Lapid

Principal Investigator

Mayo Clinic

Are You a Good Fit for This Trial?

This trial is for adults with mild cognitive impairment (MCI) who speak English fluently, have been diagnosed by a neurologist, show memory issues but not severe enough to be dementia, and are in good health. They must not be pregnant or planning pregnancy, should have stable medication use for the past month, and need a care partner for study visits.

Inclusion Criteria

Ability to provide informed consent

I can see and hear well enough to take psychological tests.

My thinking and memory skills are generally good.

Exclusion Criteria

Substance use disorder (except caffeine and nicotine) within the past 12 months

History of traumatic brain injury

conductive, ferromagnetic or other magnetic-sensitive metals implanted in their head or within 30 cm of the treatment coil (e.g., cochlear implants, implanted electrodes/stimulators, aneurysm clips or coils, stents, bullet fragments or jewelry)

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Period 1

Participants receive 10 consecutive days of daily single session of iTBS rTMS for 3.5 minutes per day over the vertex or DLPFC or LPC

2 weeks

10 visits (in-person)

Washout

Participants undergo a washout period to eliminate the effects of the first treatment before starting the second treatment period

4 weeks

Treatment Period 2

Participants receive 10 consecutive days of daily single session of iTBS rTMS for 3.5 minutes per day over the DLPFC or LPC or vertex

2 weeks

10 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• iTBS rTMS

Trial Overview The trial tests intermittent theta burst stimulation (iTBS) using repetitive transcranial magnetic stimulation (rTMS) on adults with MCI. It aims to see if this treatment is doable and can improve memory functions in participants.

How Is the Trial Designed?

Group I: iTBS rTMS Vertex then Left Dorsolateral Prefrontal Cortex (DLPFC) Experimental Treatment 1 Intervention

Subjects will receive 1 session of iTBS rTMS for 3.5 minutes daily over the vertex for 10 consecutive days in the first treatment period, complete a washout period of 4 weeks then receive 10 consecutive days of daily single session of iTBS rTMS for 3.5 minutes per day over the DLPFC.

Group II: iTBS rTMS Vertex then Lateral Parietal Cortex (LPC) Experimental Treatment 1 Intervention

Subjects will receive 1 session of iTBS rTMS for 3.5 minutes daily over the vertex for 10 consecutive days in the first treatment period, complete a washout period of 4 weeks then receive 10 consecutive days of daily single session of iTBS rTMS for 3.5 minutes per day over the LPC.

Group III: iTBS rTMS Left Dorsolateral Prefrontal Cortex (DLPFC) then Vertex Experimental Treatment 1 Intervention

Subjects will receive 10 consecutive days of daily single session of iTBS rTMS for 3.5 minutes per day over the DLPFC in the first treatment period, complete a washout period of 4 weeks then receive 1 session of iTBS rTMS for 3.5 minutes daily over the vertex for 10 consecutive days.

Group IV: iTBS rTMS Lateral Parietal Cortex (LPC) then Vertex Experimental Treatment 1 Intervention

Subjects will receive 10 consecutive days of daily single session of iTBS rTMS for 3.5 minutes per day over the LPC in the first treatment period, complete a washout period of 4 weeks then receive 1 session of iTBS rTMS for 3.5 minutes daily over the vertex for 10 consecutive days.

Group V: iTBS rTMS Vertex only Placebo Group 1 Intervention

Cognitively normal and healthy controls will receive 1 session of iTBS rTMS for 3.5 minutes daily over the vertex for 10 consecutive days. The vertex serves as a control as there are no functional improvements in cognition with stimulation of the vertex region.

Who Is Running the Clinical Trial?

Maria I. Lapid, M.D.

Lead Sponsor

Trials

1

Recruited

30+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05327257

NCT05327257 | iTBS rTMS in Mild Cognitive Impairment The purposes of this research are to test whether it is feasible to administer a treatment protocol called intermittent theta burst stimulation (iTBS) ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12465570/

Effects of intermittent theta-burst stimulation on cognition ... These findings suggest that iTBS can produce delayed cognitive enhancement in individuals with amnestic MCI and very mild AD, while the impact ...

3. pilotfeasibilitystudies.biomedcentral.com pilotfeasibilitystudies.biomedcentral.com/articles/10.1186/s40814-025-01625-5

A pilot randomized controlled double-blind trial of intermittent ... This innovative study aims to test the feasibility of iTBS as a cognitive enhancement strategy in MCI.

4. jnnp.bmj.com jnnp.bmj.com/content/95/11/1036

A phase I trial of accelerated intermittent theta burst rTMS for ... Accelerated intermittent theta burst stimulation (iTBS) rTMS protocols are promising as they substantially reduce burden by shortening the treatment course.

5. sciencedirect.com sciencedirect.com/science/article/pii/S3050529125000042

Neurocognitive effects of theta burst stimulation for ... Results suggested that TBS for TRD may produce neurocognitive enhancement across specific neurocognitive domains including executive functioning, attention, ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11963328/

A pilot randomized controlled double-blind trial of intermittent ... Our study will test the feasibility of using intermittent theta burst stimulation (iTBS) technique of rTMS in MCI, pilot test the study design, ...

7. mayo.edu mayo.edu/research/clinical-trials/cls-20533349

iTBS rTMS in Mild Cognitive Impairment - Clinical Trials About this study. To test the feasibility of conducting a 10-day Intermittent Theta Burst Stimulation (iTBS) repetitive Transcranial ...

8. clinicaltrial.be clinicaltrial.be/en/details/29755?per_page=100&only_recruiting=1&only_eligible=0&only_active=0

iTBS rTMS in Mild Cognitive Impairment Subjects will receive 10 consecutive days of daily single session of iTBS rTMS for 3.5 minutes per day over the DLPFC in the first treatment ...