Transcranial Pulse Stimulation for Dementia

Overseen By Joseph M Gullett, Ph.D.

Age: 65+

Sex: Any

Trial Phase: Academic

Sponsor: University of Florida

Must not be taking: Sedatives, Anticholinergics, CNS drugs

Disqualifiers: Neurological disorders, Major psychiatric illness, others

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 10

Duration: 2 weeks

20 Participants Needed

Trial Summary

What is the purpose of this trial?

This study will investigate transcranial pulse stimulation (TPS) as a method of enhancing cognitive and neural function. The study team will apply this low intensity, magnetically pulse technology to key brain regions in a randomized, sham-controlled trial (RCT). The study will determine the magnitude of changes in cognitive function and brain function and structure between a pre- and post-stimulation among 10 typically-aging older adults and 10 patients with mild dementia.

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

The trial requires that you avoid medications with cognitive side effects or strong anticholinergic effects. You should be stable on any recently changed medications for at least four weeks before starting the study. Your medications will be reviewed to identify any that might interfere with the trial.

What data supports the effectiveness of the treatment Neurolith Transcranial Pulse Stimulation for dementia?

Research shows that Transcranial Pulse Stimulation (TPS) can improve brain function and cognitive performance in Alzheimer's patients, a type of dementia. Studies have found that TPS enhances brain connectivity and may improve memory and language skills, although its effects on brain structure are still being studied. ^{1 2 3 4 5}

How is the treatment Neurolith Transcranial Pulse Stimulation different from other treatments for dementia?

Neurolith Transcranial Pulse Stimulation (TPS) is unique because it uses non-invasive ultrasound pulses to stimulate the brain, which can enhance brain connectivity and improve cognitive functions. Unlike traditional drug treatments, TPS directly targets brain activity without the need for medication, offering a novel approach to treating dementia. ^{1 3 4 5 6}

Research Team

Joseph M Gullett, PhD

Principal Investigator

University of Florida

Eligibility Criteria

This trial is for English-speaking men and women aged 65-84 who are physically mobile without major falls or balance issues. It includes healthy older adults and those with mild dementia, as determined by specific cognitive tests (TICS and MoCA). Exclusions include severe medical conditions, certain medication use, history of brain infections or neurological disorders, MRI contraindications like metal implants, left-handedness/ambidextrousness due to atypical brain function lateralization.

Inclusion Criteria

I am between 65 and 84 years old.

English speaking

I can move around easily and haven't had major falls or balance issues.

Exclusion Criteria

Hearing or vision deficits that will not allow for reliable standardized cognitive assessment; i.e. colorblindness, inability to hear through headphones (with or without hearing aids), macular degeneration or other significant diseases that cause severe loss of vision. If vision is corrected with lenses to appropriate levels, then participant will be eligible

I have a blood clotting disorder or thrombosis.

I cannot walk two blocks without stopping or have trouble balancing.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1 week

1 visit (in-person)

Baseline Assessment

Participants undergo pre-intervention multi-modal MRI, blood draw, and neurocognitive evaluation

1 week

1 visit (in-person)

Treatment

Participants receive thrice-weekly transcranial pulse stimulation (TPS) for two weeks

2 weeks

6 visits (in-person)

Post-intervention Assessment

Participants undergo post-intervention MRI, blood draw, and neurocognitive evaluation

1 week

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including a no-contact period and quarterly phone surveys for one year

1 year

1 phone call (7 days post-treatment), quarterly phone surveys

Treatment Details

Interventions

• Neurolith Transcranial Pulse Stimulation Active
• Neurolith Transcranial Pulse Stimulation Sham

Trial Overview The study examines transcranial pulse stimulation (TPS) using Neurolith technology on the brain. Participants will be randomly assigned to receive either active TPS or a sham (placebo-like) procedure in an effort to improve cognitive functions. The effects will be measured before and after treatment among typically aging adults and patients with mild dementia.

Participant Groups

Group I: Active brain stimulation Active Control 1 Intervention

These participants will receive focused TPS (pulsed stimulation) of the specified default mode network regions as specified in the detailed study description.

Group II: Sham brain stimulation Placebo Group 1 Intervention

These participants will also receive focused TPS (pulsed stimulation) of the specified default mode network regions as specified in the detailed study description, though the device will be set to "Sham" in a blinded fashion by the biostatistician by placing an air pouch in the device hand piece.

Neurolith Transcranial Pulse Stimulation Active is already approved in European Union for the following indications:

Approved in European Union as Neurolith Transcranial Pulse Stimulation for:

• Alzheimer's disease

Who Is Running the Clinical Trial?

University of Florida

Lead Sponsor

Trials

1,428

Recruited

987,000+

Findings from Research

Transcranial pulse stimulation (TPS) has shown significant improvements in cognitive performance and reductions in depressive symptoms among 99 Alzheimer's disease patients, as evidenced by various cognitive assessment scales.

TPS appears to be a safe treatment option, with only mild and reversible side effects reported, and no serious adverse events observed, suggesting its potential as an adjunct therapy for Alzheimer's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial pulse stimulation in Alzheimer's disease. Chen, X., You, J., Ma, H., et al.[2023]

Transcranial pulse stimulation (TPS) therapy over 2-4 weeks showed improvements in cognitive performance and functional networks in Alzheimer's disease (AD) patients, with effects lasting up to 3 months.

In a study of 17 AD patients, an increase in cortical thickness was significantly correlated with neuropsychological improvements, suggesting that TPS may help reduce cortical atrophy in critical brain areas associated with memory.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial ultrasound pulse stimulation reduces cortical atrophy in Alzheimer's patients: A follow-up study. Popescu, T., Pernet, C., Beisteiner, R.[2023]

Transcranial pulse stimulation (TPS) showed potential cognitive benefits in Alzheimer's patients, particularly in improving cognition and language, but it negatively affected visuo-constructive functions, highlighting a specific functional impact of the treatment.

In a study of 18 Alzheimer's patients, it was found that important nodes in the visuo-constructive network were not stimulated, leading to decreased network efficiency and correlating with poorer visuo-constructive test scores, suggesting that TPS may need to be tailored to target specific brain areas for optimal outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Functional Specificity of TPS Brain Stimulation Effects in Patients with Alzheimer's Disease: A Follow-up fMRI Analysis. Dörl, G., Matt, E., Beisteiner, R.[2022]

Transcranial pulse stimulation (TPS) appears to be a safe and promising add-on therapy for Alzheimer's disease, with only rare and transient side effects reported in 4% of sessions among 11 patients studied.

Patients showed significant improvements in cognitive function as measured by the ADAS and ADAS Cog tests, along with self-reported reductions in symptom severity and depressive symptoms, suggesting TPS may benefit both cognitive and emotional aspects of Alzheimer's.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Retrospective real-world pilot data on transcranial pulse stimulation in mild to severe Alzheimer's patients. Cont, C., Stute, N., Galli, A., et al.[2022]

Transcranial pulse stimulation (TPS) was found to significantly improve cognitive function in older adults with mild neurocognitive disorder (NCD) after a two-week intervention involving three sessions per week, with no serious side effects reported among the 19 participants.

The study showed improvements in various cognitive assessments, including the HK-MoCA and Stroop interference tests, suggesting TPS could help delay cognitive decline in this population, although further research is needed to explore its long-term effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial pulse stimulation in the treatment of mild neurocognitive disorders. Fong, TKH., Cheung, T., Ngan, STJ., et al.[2023]

Transcranial Pulse Stimulation (TPS) was found to significantly improve motor symptoms in 20 Parkinson's disease patients, with a notable reduction in Unified Parkinson's Disease Rating Scale part III (UPDRS-III) scores after ten treatment sessions.

The treatment was deemed safe, as no major side effects were reported during the intervention, suggesting TPS could be a beneficial add-on therapy for patients already receiving standard treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel ultrasound neuromodulation therapy with transcranial pulse stimulation (TPS) in Parkinson's disease: a first retrospective analysis. Osou, S., Radjenovic, S., Bender, L., et al.[2023]

References

1. England pubmed.ncbi.nlm.nih.gov

Transcranial pulse stimulation in Alzheimer's disease. [2023]

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

Transcranial ultrasound pulse stimulation reduces cortical atrophy in Alzheimer's patients: A follow-up study. [2023]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Functional Specificity of TPS Brain Stimulation Effects in Patients with Alzheimer's Disease: A Follow-up fMRI Analysis. [2022]

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

Retrospective real-world pilot data on transcranial pulse stimulation in mild to severe Alzheimer's patients. [2022]

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

Transcranial pulse stimulation in the treatment of mild neurocognitive disorders. [2023]

6. Germany pubmed.ncbi.nlm.nih.gov

Novel ultrasound neuromodulation therapy with transcranial pulse stimulation (TPS) in Parkinson's disease: a first retrospective analysis. [2023]