Sensory-Specific Peripheral Stimulation for Parkinson's Disease

Recruiting in Palo Alto (17 mi)

Overseen by Jose Pons, Ph.D

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: Shirley Ryan AbilityLab

Must not be taking: Seizure medications

Disqualifiers: Epilepsy, Seizures, Substance abuse, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

The purpose of this study is to understand the neurophysiological mechanisms of peripheral electrical stimulation (PES) in modulating supraspinal tremorogenic input to motoneurons. For this purpose, the investigators will use transcutaneous PES, high-density electromyography (HD-EMG), transcranial magnetic stimulation (TMS), electroencephalography (EEG), magnetic resonance imaging (MRI), and neuromusculoskeletal modelling. This study will be carried out in both healthy participants and patients with essential tremor (ET) and Parkinson's disease (PD).

Will I have to stop taking my current medications?

The trial requires that patients have stable medication doses for at least 30 days before joining, and they must be willing to stop taking tremor medications on the day of study assessments.

What data supports the effectiveness of the treatment Sensory-Specific Peripheral Stimulation for Parkinson's Disease?

Research shows that transcranial magnetic stimulation (TMS), a component of the treatment, can improve motor function in Parkinson's disease patients, with a modest positive effect. Additionally, a case study using a similar method, T-PEMF, reported improvements in motor function and handwriting in a Parkinson's patient. ^{1 2 3 4 5}

Is sensory-specific peripheral stimulation safe for humans?

Transcranial magnetic stimulation (TMS), a similar technique, has been used in various studies and is generally safe, but there is a slight risk of seizures and other side effects. In patients with Parkinson's disease, TMS has been used safely, but caution is advised for those with deep brain stimulation implants due to potential electrical interference. ^{6 7 8 9 10}

How does the treatment Sensory-Specific Peripheral Stimulation for Parkinson's Disease differ from other treatments?

This treatment is unique because it combines peripheral electrical stimulation (using small electrical currents on the skin) with transcranial magnetic stimulation (using magnetic fields to stimulate the brain) to target sensory processing issues in Parkinson's disease, which are not typically addressed by standard dopaminergic treatments. ^{1 3 7 11 12}

Research Team

Jose Pons, Ph.D

Principal Investigator

Shirley Ryan AbilityLab

Eligibility Criteria

This trial is for adults aged 18-80 with moderate to severe tremor due to Parkinson's Disease or Essential Tremor, without other neurological disorders. Participants must have stable medication doses for at least 30 days and be able to understand English and consent. Exclusions include metal implants, pacemakers, substance abuse, pregnancy, mixed tremors, dementia, significant head trauma or diseases that could interfere with the study.

Inclusion Criteria

My medication doses have been the same for the last 30 days.

I understand the study and agree to participate.

You have significant hand tremors, as determined by a doctor's assessment and specific tremor rating scales.

Exclusion Criteria

You have a cochlear implant.

I do not have any neurological, heart, kidney, liver, cancer, or mental health conditions that would affect the study.

I cannot or will not stop my tremor medications for assessments.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Experiment A

Healthy participants undergo PES, TMS, and MRI to study neurophysiological mechanisms

3 months

Multiple visits with different stimulation patterns

Experiment B

Patients with ET or PD undergo PES, TMS, and MRI to study tremor reduction strategies

6 months

Multiple visits with different stimulation patterns

Follow-up

Participants are monitored for long-term effects of PES on motor inhibition and tremor reduction

1 week

Treatment Details

Interventions

• Peripheral electrical stimulation (Device)
• Single pulse TMS (Device)

Trial Overview The study aims to explore how peripheral electrical stimulation (PES) affects brain signals that cause tremors in patients with Essential Tremor (ET) and Parkinson's Disease (PD). It involves non-invasive techniques like TMS and EEG along with MRI imaging in both healthy individuals and those affected by ET or PD.

Participant Groups

Group I: Patients Experimental Treatment 2 Interventions

Participants with Parkinson's Disease or essential tremor will be scanned with MRI and undergo PES and/or single pulse TMS during several visits, each with different stimulation patterns, while HD-EMG and EEG are recorded.

Group II: Healthy Participants Experimental Treatment 2 Interventions

Healthy participants without motor disorders and medications influencing brain functions will be scanned with MRI and undergo PES and/or single pulse TMS during several visits, each with different stimulation patterns, while HD-EMG is recorded.

Who Is Running the Clinical Trial?

Shirley Ryan AbilityLab

Lead Sponsor

Trials

212

Recruited

17,900+

Dr. Pablo Celnik

Shirley Ryan AbilityLab

Chief Executive Officer since 2023

MD from University of Buenos Aires Faculty of Medical Sciences

Dr. James Sliwa

Shirley Ryan AbilityLab

Chief Medical Officer since 2021

DO

Northwestern University

Collaborator

Trials

1,674

Recruited

989,000+

Dr. Jeffrey Sherman

Northwestern University

Chief Medical Officer

MD from Northwestern University

Dr. Alicia Löffler

Northwestern University

Chief Executive Officer since 2010

PhD from the University of Massachusetts at Amherst, post-doctoral training at Caltech

Findings from Research

In a study involving 22 patients with Parkinson's disease, various rTMS protocols were tested over 5 days, but none showed significant improvement over placebo in enhancing motor function.

The only notable result was in the Purdue Pegboard Test, where all active rTMS protocols performed slightly better than sham stimulation, indicating that while rTMS may have some effects, motor training and medication likely played a larger role in observed improvements.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Training effects outweigh effects of single-session conventional rTMS and theta burst stimulation in PD patients. Rothkegel, H., Sommer, M., Rammsayer, T., et al.[2019]

A 62-year-old man with Parkinson's disease showed significant improvements in handwriting and motor function after receiving bipolar pulsed electromagnetic stimulation (T-PEMF) for 30 minutes a day over three 8-week periods.

The treatment led to a notable decrease in motor symptoms, as indicated by a reduction in UPDRS scores, and the benefits lasted for about three months, suggesting T-PEMF may have potential as a non-pharmacological therapy for Parkinson's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of Long-Term Treatment with T-PEMF on Forearm Muscle Activation and Motor Function in Parkinson's Disease. Jensen, BR., Malling, ASB., Morberg, BM., et al.[2020]

In a study involving 14 patients with Parkinson's disease and 13 control subjects, it was found that dopaminergic treatment alters sensory perception, specifically in how patients respond to tactile stimuli compared to healthy individuals.

Transcranial magnetic stimulation revealed that while healthy controls showed increased sensory responses at certain stimulus intervals, patients on dopaminergic treatment did not, indicating that this treatment may affect the excitability of the primary somatosensory cortex and sensory integration in Parkinson's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sensory perception changes induced by transcranial magnetic stimulation over the primary somatosensory cortex in Parkinson's disease. Palomar, FJ., Díaz-Corrales, F., Carrillo, F., et al.[2011]

Repetitive transcranial magnetic stimulation (rTMS) showed a significant short-term improvement in walking performance for individuals with Parkinson's disease, as evidenced by a meta-analysis of 14 studies involving 298 participants.

However, the benefits of rTMS did not persist in the long term, and there were no significant differences in measures like the Timed Up and Go test or the freezing of gait questionnaire between rTMS and control groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of Repetitive Transcranial Magnetic Stimulation on Gait and Freezing of Gait in Parkinson Disease: A Systematic Review and Meta-analysis. Xie, YJ., Gao, Q., He, CQ., et al.[2020]

Transcranial magnetic stimulation (TMS) has a modest but significant positive effect on motor function in patients with Parkinson's disease, with a pooled effect size of 0.62 based on 12 studies.

Electroconvulsive therapy (ECT) shows a stronger effect on motor function in Parkinson's disease patients, with a pooled effect size of 1.68 from five studies, indicating it may be a more effective treatment option for motor dysfunction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Non-invasive brain stimulation for Parkinson's disease: a systematic review and meta-analysis of the literature. Fregni, F., Simon, DK., Wu, A., et al.[2022]

Transcranial static magnetic field stimulation (tSMS) effectively decreases cortical excitability in patients with Parkinson's disease when they are OFF their medication, as shown by reduced motor evoked potentials (MEPs) after 10 minutes of stimulation.

The effects of tSMS are influenced by the patient's medication status, with variability in response observed when patients are ON medication, suggesting that dopamine levels play a crucial role in how tSMS affects cortical excitability.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dopamine-dependent changes of cortical excitability induced by transcranial static magnetic field stimulation in Parkinson's disease. Dileone, M., Carrasco-López, MC., Segundo-Rodriguez, JC., et al.[2019]

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]

Transcranial magnetic stimulation (TMS) has a very low seizure risk, with only 0.08 seizures reported per 1,000 sessions, and less than 0.02 seizures per 1,000 sessions when guidelines are followed for individuals without known risk factors.

The study found that exceeding safety guidelines increases the risk of seizures, and seizures are more likely to occur during the first few TMS sessions, suggesting that TMS is generally safe when administered properly.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Seizures from transcranial magnetic stimulation 2012-2016: Results of a survey of active laboratories and clinics. Lerner, AJ., Wassermann, EM., Tamir, DI.[2021]

In patients with Parkinson's disease (PD), transcranial magnetic stimulation (TMS) revealed that their muscle responses during sustained contractions differed significantly from healthy individuals, indicating potential impairments in their motor control mechanisms.

While healthy subjects showed predictable changes in muscle excitability during fatigue, PD patients exhibited inconsistent responses, suggesting a disruption in the balance between cortical excitation and inhibition during challenging motor tasks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Changes in motor cortex excitability associated with muscle fatigue in patients with Parkinson's disease. Milanović, S., Filipović, SR., Radovanović, S., et al.[2019]

In a study involving 10 patients with idiopathic Parkinson's disease (IPD), 10 patients with multiple system atrophy of the parkinsonian type (MSA-P), and 10 control subjects, it was found that patients with IPD showed a significant impairment in processing proprioceptive information induced by muscle vibration compared to controls.

The results indicated that while controls exhibited a clear enhancement in motor evoked potentials (MEPs) due to muscle vibration, this response was absent in IPD patients and less pronounced in MSA-P patients, suggesting that proprioceptive processing deficits may contribute to motor difficulties in these conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Changes in processing of proprioceptive information in Parkinson's disease and multiple system atrophy. Schrader, C., Peschel, T., Däuper, J., et al.[2008]

References

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

Training effects outweigh effects of single-session conventional rTMS and theta burst stimulation in PD patients. [2019]

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

Effects of Long-Term Treatment with T-PEMF on Forearm Muscle Activation and Motor Function in Parkinson's Disease. [2020]

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

Sensory perception changes induced by transcranial magnetic stimulation over the primary somatosensory cortex in Parkinson's disease. [2011]

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

Effect of Repetitive Transcranial Magnetic Stimulation on Gait and Freezing of Gait in Parkinson Disease: A Systematic Review and Meta-analysis. [2020]

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

Non-invasive brain stimulation for Parkinson's disease: a systematic review and meta-analysis of the literature. [2022]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Somatosensory inputs modulate the excitability of cerebellar-cortical interaction. [2021]

7. England pubmed.ncbi.nlm.nih.gov

Dopamine-dependent changes of cortical excitability induced by transcranial static magnetic field stimulation in Parkinson's disease. [2019]

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

Transcranial magnetic stimulation in the presence of deep brain stimulation implants: Induced electrode currents. [2021]

9. England pubmed.ncbi.nlm.nih.gov

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

10. Netherlands pubmed.ncbi.nlm.nih.gov

Seizures from transcranial magnetic stimulation 2012-2016: Results of a survey of active laboratories and clinics. [2021]

11. Serbia pubmed.ncbi.nlm.nih.gov

Changes in motor cortex excitability associated with muscle fatigue in patients with Parkinson's disease. [2019]

12. Netherlands pubmed.ncbi.nlm.nih.gov

Changes in processing of proprioceptive information in Parkinson's disease and multiple system atrophy. [2008]