rTMS for Progressive Supranuclear Palsy

Overseen By Graham Harker

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Oregon Health and Science University

Must be taking: Cholinergic, Dopaminergic, Serotonergic, NMDA antagonists

Disqualifiers: Neurological disorders, Vestibular disorders, others

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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 8

30 Participants Needed

Trial Summary

What is the purpose of this trial?

The objective of this proposal is to investigate the effect of non-invasive repetitive cerebellar transcranial magnetic stimulation (rTMS) on motor control in progressive supranuclear (PSP). The central hypothesis is that augmenting cerebellar inhibition via cerebellar rTMS will decrease postural instability in patients with PSP. We will use functional near infrared spectroscopy (fNIRS) to examine changes in motor and premotor cortical activity after cerebellar rTMS.

Will I have to stop taking my current medications?

You can stay on your current medications as long as the doses are stable and they are cholinergic, dopaminergic, serotonergic sedatives, or NMDA receptor antagonists.

What data supports the effectiveness of the treatment Repetitive Transcranial Magnetic Stimulation (rTMS) for Progressive Supranuclear Palsy?

Research shows that rTMS can lead to modest and temporary improvements in symptoms for patients with Progressive Supranuclear Palsy, particularly in balance and stability. Additionally, rTMS has been effective in improving language functions in other neurodegenerative conditions, suggesting potential benefits for similar disorders. ^{1 2 3 4 5}

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

Repetitive transcranial magnetic stimulation (rTMS) is generally considered safe, with guidelines established to minimize risks. Some studies report a slight risk of seizures and other adverse effects, but these are rare. Safety guidelines have been updated over the years to ensure safe application in both healthy individuals and those with various conditions. ^{6 7 8 9 10}

How does the treatment rTMS differ from other treatments for Progressive Supranuclear Palsy?

Repetitive transcranial magnetic stimulation (rTMS) is unique because it is a non-invasive treatment that uses magnetic fields to stimulate nerve cells in the brain, which is different from traditional drug therapies. It has shown modest and temporary improvements in symptoms of Progressive Supranuclear Palsy, a condition for which no specific treatments currently exist. ^{1 3 4 5 11}

Research Team

Marian L Dale, MD, MCR

Principal Investigator

Oregon Health and Science University

Eligibility Criteria

This trial is for adults aged 40-85 with progressive supranuclear palsy (PSP) who can follow simple instructions and walk independently with a walker. They must not start new therapies during the study, be on stable medication doses, and women of childbearing age need to use reliable birth control.

Inclusion Criteria

Ability to read at 6th grade reading level in English

I can keep my current doses of brain-related medications stable during the study.

I can avoid starting new physical or speech therapy during the study.

Exclusion Criteria

I do not have major nerve or balance disorders.

You have any electronic, magnetic, or mechanical implants, or have had metal in your eyes, head, or body that could cause harm.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Assessment

Participants undergo baseline assessments before starting the intervention

1 week

TMS Intervention

Participants receive a 2-week TMS intervention or sham treatment

2 weeks

4 visits (in-person)

Washout Period

A 1-month washout period between TMS and sham treatments

4 weeks

Sham TMS or TMS Intervention

Participants receive a 2-week sham TMS or TMS intervention

2 weeks

4 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Repetitive transcranial magnetic stimulation (rTMS)

Trial Overview The trial tests if non-invasive brain stimulation called repetitive transcranial magnetic stimulation (rTMS) can improve motor control in PSP patients by targeting the cerebellum. Changes in brain activity will be monitored using functional near infrared spectroscopy (fNIRS).

Participant Groups

Group I: Sham treatment first Experimental Treatment 1 Intervention

After completing their baseline assessment, participants randomized to this arm will initially take part in a 2-week sham TMS period. After the midpoint assessment and subsequent a 1-month washout, these participants will then complete a 2-week TMS intervention prior to their final assessment.

Group II: Active TMS first Experimental Treatment 1 Intervention

After completing their baseline assessment, participants randomized to this arm will initially take part in a 2-week TMS intervention. After the midpoint assessment and subsequent a 1-month washout, these participants will then complete a 2-week sham TMS period prior to their final assessment.

Repetitive transcranial magnetic stimulation (rTMS) is already approved in United States, European Union, Canada for the following indications:

Approved in United States as rTMS for:

• Major depressive disorder
• Obsessive-compulsive disorder
• Migraine prevention

Approved in European Union as rTMS for:

• Major depressive disorder
• Obsessive-compulsive disorder

Approved in Canada as rTMS for:

• Major depressive disorder
• Obsessive-compulsive disorder

Who Is Running the Clinical Trial?

Oregon Health and Science University

Lead Sponsor

Trials

1,024

Recruited

7,420,000+

National Center of Neuromodulation for Rehabilitation

Collaborator

Trials

12

Recruited

240+

National Institute of Neurological Disorders and Stroke (NINDS)

Collaborator

Trials

1,403

Recruited

655,000+

Collins Medical Trust

Collaborator

Trials

6

Recruited

410+

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Collaborator

Trials

2,103

Recruited

2,760,000+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

Department of Health and Human Services

Collaborator

Trials

240

Recruited

944,000+

National Center for Advancing Translational Sciences (NCATS)

Collaborator

Trials

394

Recruited

404,000+

National Center of Neuromodulation for Rehabilitation (NC-NM4R)

Collaborator

Trials

1

Recruited

30+

Findings from Research

In a small group of patients with progressive supranuclear palsy, treatment with rapid-rate repetitive transcranial magnetic stimulation over five days led to modest and temporary improvements in symptoms, particularly those affecting posture and balance.

No side effects were reported during the treatment, suggesting that this intervention may be safe for patients with this neurodegenerative disorder.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repetitive transcranial magnetic stimulation in patients with progressive supranuclear palsy: a pilot study. Santens, P., Sieben, A., De Letter, M.[2009]

High frequency repetitive Transcranial Magnetic Stimulation (hf-rTMS) applied to the left prefrontal cortex showed significant and lasting improvements in linguistic skills for a patient with Primary Progressive Aphasia (PPA).

The study indicates that hf-rTMS may enhance neural connections in areas affected by metabolic dysfunction, suggesting its potential as a therapeutic tool for neurodegenerative aphasia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A case study of Primary Progressive Aphasia: improvement on verbs after rTMS treatment. Finocchiaro, C., Maimone, M., Brighina, F., et al.[2022]

Theta burst repetitive transcranial magnetic stimulation (rTMS) significantly improved postural stability in 20 patients with progressive supranuclear palsy (PSP), as evidenced by increased time without falls and enhanced balance metrics during specific tasks.

The study utilized a double-blind crossover design, showing that real rTMS led to measurable improvements in sway parameters compared to sham stimulation, suggesting that non-invasive brain stimulation could be a promising avenue for treating PSP.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cerebellar rTMS in PSP: a Double-Blind Sham-Controlled Study Using Mobile Health Technology. Pilotto, A., Rizzetti, MC., Lombardi, A., et al.[2022]

High-frequency repetitive transcranial magnetic stimulation (rTMS) applied to the dorsolateral prefrontal cortex significantly improved language functions in patients with primary progressive aphasia (PPA), as evidenced by higher scores on the Boston Naming Test (BNT) and Western Aphasia Battery (WAB) compared to a sham treatment over a 6-month follow-up.

The improvements in language abilities were consistent across different variants of PPA, and significant enhancements in communicative activity were also noted at 1 and 3 months post-treatment, indicating the sustained efficacy of rTMS in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of primary progressive aphasia by repetitive transcranial magnetic stimulation: a randomized, double-blind, placebo-controlled study. Huang, Y., Tan, Y., Hao, H., et al.[2023]

High-frequency repetitive transcranial magnetic stimulation (hf-rTMS) applied to the left dorso-lateral prefrontal cortex showed a significant temporary improvement in linguistic skills in a patient with logopenic variant primary progressive aphasia (LPPA).

The study suggests that hf-rTMS may enhance language abilities by promoting long-term potentiation and synaptic plasticity in the brain areas involved in language, indicating potential for future research into its therapeutic use for LPPA and other neurodegenerative disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repetitive deep transcranial magnetic stimulation improves verbal fluency and written language in a patient with primary progressive aphasia-logopenic variant (LPPA). Trebbastoni, A., Raccah, R., de Lena, C., et al.[2022]

A review of 84 single pulse and paired-pulse TMS studies with 1091 Parkinson's disease patients, and 77 repetitive TMS studies with 1137 patients, found a very low risk of adverse events, with no seizures reported.

The overall risk of adverse events from rTMS was 0.040 per patient, with common side effects being mild and transient, such as headaches and scalp pain, indicating that TMS is generally safe for Parkinson's patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of transcranial magnetic stimulation in Parkinson's disease: a review of the literature. Vonloh, M., Chen, R., Kluger, B.[2021]

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]

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 study involving 18 subjects with major depression, repetitive transcranial magnetic stimulation (rTMS) for up to 4 weeks was found to be generally safe, with no significant mean deficits in neuropsychologic function or auditory thresholds.

However, two patients experienced mild high-frequency hearing loss, indicating that while rTMS is safe for most, individual responses may vary and warrant further investigation into long-term safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of a 2- to 4-week course of repetitive transcranial magnetic stimulation (rTMS) on neuropsychologic functioning, electroencephalogram, and auditory threshold in depressed patients. Loo, C., Sachdev, P., Elsayed, H., et al.[2019]

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 28 Parkinson's disease (PD) and 23 Progressive Supranuclear Palsy (PSP) patients, both conditions showed similar increases in motor evoked potential (MEP) amplitude compared to healthy controls, suggesting shared neurophysiological characteristics at early stages.

The resting motor threshold (rMT) was positively correlated with cognitive performance in PSP patients, indicating that rMT may serve as an early indicator of cognitive decline in this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical and Electrophysiological Hints to TMS in De Novo Patients with Parkinson's Disease and Progressive Supranuclear Palsy. Fisicaro, F., Lanza, G., Cantone, M., et al.[2020]

References

1. Italy pubmed.ncbi.nlm.nih.gov

Repetitive transcranial magnetic stimulation in patients with progressive supranuclear palsy: a pilot study. [2009]

2. England pubmed.ncbi.nlm.nih.gov

A case study of Primary Progressive Aphasia: improvement on verbs after rTMS treatment. [2022]

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

Cerebellar rTMS in PSP: a Double-Blind Sham-Controlled Study Using Mobile Health Technology. [2022]

4. Austria pubmed.ncbi.nlm.nih.gov

Treatment of primary progressive aphasia by repetitive transcranial magnetic stimulation: a randomized, double-blind, placebo-controlled study. [2023]

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

Repetitive deep transcranial magnetic stimulation improves verbal fluency and written language in a patient with primary progressive aphasia-logopenic variant (LPPA). [2022]

6. England pubmed.ncbi.nlm.nih.gov

Safety of transcranial magnetic stimulation in Parkinson's disease: a review of the literature. [2021]

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

Side effects of repetitive transcranial magnetic stimulation. [2005]

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

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

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

Effects of a 2- to 4-week course of repetitive transcranial magnetic stimulation (rTMS) on neuropsychologic functioning, electroencephalogram, and auditory threshold in depressed patients. [2019]

10. 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]

11. Switzerland pubmed.ncbi.nlm.nih.gov

Clinical and Electrophysiological Hints to TMS in De Novo Patients with Parkinson's Disease and Progressive Supranuclear Palsy. [2020]