Sensory-Specific Peripheral Stimulation for Parkinson's Disease
Recruiting in Palo Alto (17 mi)
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.12345
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.678910
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.1371112
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.
See 11 more
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.
See 23 more
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 OverviewThe 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
2Treatment groups
Experimental Treatment
Group I: PatientsExperimental Treatment2 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 ParticipantsExperimental Treatment2 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
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Shirley Ryan AbilityLabChicago, IL
Loading ...
Who Is Running the Clinical Trial?
Shirley Ryan AbilityLabLead Sponsor
Northwestern UniversityCollaborator
References
Training effects outweigh effects of single-session conventional rTMS and theta burst stimulation in PD patients. [2019]Focal single-session repetitive transcranial magnetic stimulation (rTMS) of the primary motor cortex has been claimed to be capable of improving motor function in Parkinson's disease.
Effects of Long-Term Treatment with T-PEMF on Forearm Muscle Activation and Motor Function in Parkinson's Disease. [2020]Bipolar pulsed electromagnetic stimulation applied to the brain (T-PEMF) is a non-pharmacological treatment which has been shown to stimulate nerve growth, attenuate nerve abnormalities, and improve microcirculation. We report on a 62-year-old, medically well-treated man with idiopathic Parkinson's disease. He was treated with T-PEMF, 30 min per day for three 8-week periods separated by two 1-week breaks. The disease made his handwriting impossible to read mainly due to small letters and lack of fluency. Forearm EMG measured during standardized conditions showed an involuntary spiky EMG pattern with regular burst activity (on his left side) at baseline. The intervention normalized the handwriting and forearm EMG. The UPDRS-motor score decreased from 25 to 17, and UPDRS-II-handwriting decreased from a pre-intervention value of 3 to 0 after the intervention. Finally, the patient reported improved fine motor function, less muscle stiffness, less muscle cramps and tingling, and less fatigue during the day in response to the T-PEMF treatment. The improved handwriting lasted for approximately 3 months after the treatment. Our results should be considered as preliminary, and large-scale, controlled studies are recommended to elucidate the therapeutic potential of long-term treatment with T-PEMF.
Sensory perception changes induced by transcranial magnetic stimulation over the primary somatosensory cortex in Parkinson's disease. [2011]Sensory symptoms are common nonmotor manifestations of Parkinson's disease. It has been hypothesized that abnormal central processing of sensory signals occurs in Parkinson's disease and is related to dopaminergic treatment. The objective of this study was to investigate the alterations in sensory perception induced by transcranial magnetic stimulation of the primary somatosensory cortex in patients with Parkinson's disease and the modulatory effects of dopaminergic treatment. Fourteen patients with Parkinson's disease with and without dopaminergic treatment and 13 control subjects were included. Twenty milliseconds after peripheral electrical tactile stimuli in the contralateral thumb, paired-pulse transcranial magnetic stimulation over the right primary somatosensory cortex was delivered. We evaluated the perception of peripheral electrical tactile stimuli at 2 conditioning stimulus intensities, set at 70% and 90% of the right resting motor threshold, using different interstimulus intervals. At 70% of the resting motor threshold, paired-pulse transcranial magnetic stimulation over the right primary somatosensory cortex induced an increase in positive responses at short interstimulus intervals (1-7 ms) in controls but not in patients with dopaminergic treatment. At 90% of the resting motor threshold, controls and patients showed similar transcranial magnetic stimulation effects. Changes in peripheral electrical tactile stimuli perception after paired-pulse transcranial magnetic stimulation over the primary somatosensory cortex are altered in patients with Parkinson's disease with dopaminergic treatment compared with controls. These findings suggest that primary somatosensory cortex excitability could be involved in changes in somatosensory integration in Parkinson's disease with dopaminergic treatment.
Effect of Repetitive Transcranial Magnetic Stimulation on Gait and Freezing of Gait in Parkinson Disease: A Systematic Review and Meta-analysis. [2020]The purpose of this review was to systematically assess the effectiveness of repetitive transcranial magnetic stimulation (rTMS) intervention on gait in individuals with Parkinson disease (PD).
Non-invasive brain stimulation for Parkinson's disease: a systematic review and meta-analysis of the literature. [2022]A systematic review and meta-analysis were conducted to quantify the efficacy of transcranial magnetic stimulation (TMS) and electroconvulsive therapy (ECT) for the treatment of motor dysfunction in patients with Parkinson's disease (PD). Prospective studies which evaluated the effects of either TMS (12 studies) or ECT (five studies) on motor function in PD using the motor subscale of the Unified Parkinson's Disease Rating Scale (UPDRS) for TMS studies and any continuous measures of motor function in PD for ECT studies were included. The pooled effect size (standardised mean difference between pre-treatment versus post-treatment means) from a random effects model was 0.62 (95% confidence interval: 0.38, 0.85) for TMS treatment and 1.68 (0.79, 2.56) for ECT treatment, and from a fixed effects model was 0.59 (0.39, 0.78) for TMS treatment and 1.55 (1.07, 2.03) for ECT treatment. TMS, across applied stimulation sites and parameters, can exert a significant, albeit modest, positive effect on the motor function of patients with PD. ECT also may exert a significant effect on motor function in PD patients.
Somatosensory inputs modulate the excitability of cerebellar-cortical interaction. [2021]Transcranial magnetic stimulation (TMS) delivered over the cerebellum 5-7 ms prior to a stimulus over the contralateral primary motor cortex (M1) reduces the excitability of M1 output, a phenomenon termed cerebellar brain inhibition (CBI). The cerebellum receives sensory information for adaptive motor coordination and motor planning. Here, we explored through TMS whether a peripheral electrical stimulus modulates CBI.
Dopamine-dependent changes of cortical excitability induced by transcranial static magnetic field stimulation in Parkinson's disease. [2019]Transcranial static magnetic field stimulation (tSMS) is a recent low-cost non-invasive brain stimulation technique that decreases cortical excitability in healthy subjects. The objective of the present study was to test the ability of tSMS to modulate cortical excitability in patients with Parkinson's disease. We performed a randomized double-blind sham-controlled cross-over study to assess cortical excitability before and immediately after tSMS (or sham) applied for 10 min to the more affected motor cortex of patients with Parkinson's disease. Cortical excitability was quantified by the amplitude of motor evoked potentials (MEPs) elicited by single-pulse transcranial magnetic stimulation (TMS). tSMS significantly decreased MEP amplitudes in patients OFF medication (after overnight withdrawal of dopaminergic drugs), but not ON medication (after an acute dose of levodopa). The between-patients variability of tSMS-induced changes was significantly greater ON medication. The variability ON medication could be partly explained by disease progression, i.e. the more advanced the patient, the more likely it was to observe a switch from inhibitory tSMS plasticity OFF medication to paradoxical facilitatory plasticity ON medication. These results suggest that tSMS induces dopamine-dependent changes of cortical excitability in patients with Parkinson's disease.
Transcranial magnetic stimulation in the presence of deep brain stimulation implants: Induced electrode currents. [2021]The safety of transcranial magnetic stimulation (TMS) in patients with an implanted deep brain stimulation (DBS) systems has not been thoroughly investigated. One potential safety hazard is the induction of significant voltages in the subcutaneous leads in the scalp that could result in unintended electrical currents in the DBS electrode contacts. We measured ex-vivo the TMS-induced voltages and currents in DBS electrodes with the implantable pulse generator (IPG) set in various modes of operation. We show that voltages as high as 100 V resulting in currents as high as 83 mA can be induced in the DBS leads by a TMS pulse in all IPG modes. These currents are an order of magnitude higher than the normal DBS pulses, and could result in tissue damage. When the IPG is turned off, electrode currents flow only if the TMS-induced voltage exceeds 5 V.
Safety of transcranial magnetic stimulation in Parkinson's disease: a review of the literature. [2021]Transcranial magnetic stimulation (TMS) has been used in both physiological studies and, more recently, the therapy of Parkinson's disease (PD). Prior TMS studies in healthy subjects and other patient populations demonstrate a slight risk of seizures and other adverse events. Our goal was to estimate these risks and document other safety concerns specific to PD patients.
Seizures from transcranial magnetic stimulation 2012-2016: Results of a survey of active laboratories and clinics. [2021]Transcranial magnetic stimulation (TMS) can cause seizures in healthy individuals and patients. However, the rate at which this occurs is unknown. We estimated the risk of seizure and other adverse events with TMS.
Changes in motor cortex excitability associated with muscle fatigue in patients with Parkinson's disease. [2019]Transcranial magnetic stimulation (TMS) is a standard technique for noninvasive assessment of changes in central nervous system excitability. The aim of this study was to examine changes in responses to TMS in patients suffering from Parkinson's disease (PD) during sustained submaximal isometric voluntary contraction [60% of maximal voluntary contraction (MVC)] of the adductor pollicis muscle, as well as during a subsequent recovery period.
Changes in processing of proprioceptive information in Parkinson's disease and multiple system atrophy. [2008]Changes in processing of proprioceptive information are known in idiopathic Parkinson's disease (IPD) and may contribute to motor deficits. This study used transcranial magnetic stimulation (TMS) to investigate the processing of proprioceptive information induced by muscle vibration (MV) in 10 patients with IPD and 10 patients with multiple system atrophy of the parkinsonian type (MSA-P) in comparison to 10 controls.