Sensory-Specific Peripheral Stimulation for Parkinson's Disease

Overseen By Jose Pons, Ph.D

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Shirley Ryan AbilityLab

Must not be taking: Seizure medications

Disqualifiers: Epilepsy, Seizures, Substance abuse, others

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

Compensation: Varies

Number of Visits: Unknown

180 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how peripheral electrical stimulation (PES) might help manage tremors in people with Parkinson’s disease and essential tremor. The researchers aim to determine whether PES can alter the brain's signals that cause these tremors. Participants will undergo various tests and scans, including transcranial magnetic stimulation (a method of stimulating the brain) and electromyography (a test to study muscle activity). Ideal candidates include individuals with essential tremor or Parkinson’s disease who experience significant tremors in their arms.

As an unphased trial, this study offers participants the chance to contribute to groundbreaking research that could lead to new treatments for tremors.

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 prior data suggests that peripheral electrical stimulation and single pulse TMS are safe for use in this study?

Research has shown that peripheral electrical stimulation (PES) is generally safe and can help reduce tremors in conditions like essential tremor and Parkinson's disease. Most people tolerate it well, with no major safety issues reported. Studies suggest that single pulse transcranial magnetic stimulation (TMS) poses no risk for people with Parkinson's disease. When users follow the recommended guidelines, it is considered safe. Both treatments have been used in clinical settings and maintain positive safety records. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it explores novel ways to manage Parkinson's Disease symptoms through sensory-specific peripheral stimulation techniques. Unlike traditional treatments like medication or deep brain stimulation, which target dopamine levels or brain structures, peripheral electrical stimulation (PES) and single pulse transcranial magnetic stimulation (TMS) focus on non-invasive methods that stimulate the nervous system differently. This approach could offer a complementary option with potentially fewer side effects and more customizable treatments, as the stimulation patterns can be tailored to each individual's needs. By using advanced imaging techniques like MRI and monitoring tools like HD-EMG and EEG, researchers hope to uncover new insights into how these methods can modify brain activity and improve motor function.

What evidence suggests that this trial's treatments could be effective for Parkinson's disease?

Research has shown that peripheral electrical stimulation (PES) can greatly reduce tremors in people with Parkinson's disease (PD). One study found that tremors decreased by nearly 50%, indicating that PES can effectively manage PD symptoms. In this trial, some participants will receive PES. Similarly, single pulse transcranial magnetic stimulation (TMS) has been found to improve movement problems in PD patients. TMS can reduce tremors for at least 24 hours after just one session. Other participants in this trial will receive TMS. Both treatments show promise in easing the symptoms of Parkinson’s disease. ^{1 2 5 6 7}

Who Is on the Research Team?

Jose Pons, Ph.D

Principal Investigator

Shirley Ryan AbilityLab

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Peripheral electrical stimulation
• Single pulse TMS

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.

How Is the Trial Designed?

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.

Peripheral electrical stimulation is already approved in United States, European Union for the following indications:

Approved in United States as Peripheral Electrical Stimulation for:

• Essential Tremor
• Parkinson's Disease

Approved in European Union as Peripheral Electrical Stimulation for:

• Essential Tremor
• Parkinson's Disease

Who Is Running the Clinical Trial?

Shirley Ryan AbilityLab

Lead Sponsor

Trials

212

Recruited

17,900+

Northwestern University

Collaborator

Trials

1,674

Recruited

989,000+

Published Research Related to This Trial

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]

Transcranial magnetic stimulation (TMS) can induce dangerously high voltages (up to 100 V) and currents (up to 83 mA) in deep brain stimulation (DBS) leads, which are significantly higher than normal DBS operation levels.

These induced currents pose a risk of tissue damage, especially when the implantable pulse generator (IPG) is turned off, as currents only flow if the TMS-induced voltage exceeds 5 V.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial magnetic stimulation in the presence of deep brain stimulation implants: Induced electrode currents. Deng, ZD., Lisanby, SH., Peterchev, AV.[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]

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 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]

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]

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]

In a study involving 12 healthy subjects, peripheral electrical stimulation of the right median nerve was found to significantly weaken cerebellar brain inhibition (CBI) when delivered 25 ms and 35 ms before cerebellar stimulation, indicating a modulation of motor cortex excitability.

The results suggest that the interaction between sensory inputs and cerebellar activity could play a crucial role in motor coordination and may have implications for understanding motor tasks and neuropsychiatric disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Somatosensory inputs modulate the excitability of cerebellar-cortical interaction. Bonassi, G., Pelosin, E., Lagravinese, G., et al.[2021]

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]

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]

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]

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Non-invasive electrical stimulation of peripheral nerves has emerged as a safe and effective strategy for reducing pathologic tremor in essential tremor.