Non-invasive Neurostimulation in Parkinson's Disease

Study Overview
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Brief Summary
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In this study, the investigators aim to investigate the effects of non-invasive neurostimulation - low-intensity transcranial electrical stimulation in conjunction with transcranial ultrasound (TUS)- on the motor symptoms associated with Parkinson's disease. The investigators want to see if there is a difference between active and sham stimulation on these motor symptoms.

Official Title
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Effects of Non-invasive Neurostimulation Methods on Motor Function in Parkinson's Disease Patients.

Conditions
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Parkinson's Disease

Intervention / Treatment
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* Procedure: low-intensity transcranial electrical stimulation
* Procedure: transcranial ultrasound


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Documentation of PD diagnosis from their clinician by either a letter or verification through their medical record Research criteria of possible or probable PD, as defined by Gelb et al (Gelb D, Oliver E, Gilman S. Diagnostic Criteria for Parkinson Disease. Arch Neurol.1999;56:33-39)[1] Age 40 or over; Taking stable medications for at least 30 days Exclusion Criteria: Features suggestive of other causes of parkinsonism/Parkinson's-plus syndromes; History of deep brain stimulation or ablation surgery, mass brain lesions; History of schizophrenia, schizoaffective disorder, other psychosis, episode of bipolar illness, alcohol/drug abuse within the past year; Need for rapid clinical response due to conditions such as initiation, psychosis, or suicidal; Contraindications to transcranial brain stimulation or TUS, i.e. metal in the head, implanted brain medical devices, etc; Unstable medical conditions (e.g. uncontrolled diabetes, uncompensated cardiac issues, heart failure, pulmonary issues, or chronic obstructive pulmonary disease); Pregnancy. Epilepsy or disorders that increase likelihood of seizures including: moderate or severe traumatic brain injury, congenital birth defects leading to seizures, brain tumor, metabolism disorders associated with seizures, and nonlacunar stroke.

Ages Eligible for Study
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Minimum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Active Electrical Stim/Active Ultrasound<br>Subjects will undergo active low-intensity transcranial electrical stimulation in conjunction with active transcranial ultrasound for 20 minutes. | Procedure: low-intensity transcranial electrical stimulation<br>* Subjects will undergo 20 minutes of low-intensity transcranial electrical stimulation of up to 2mA. During active stimulation, the current will be active for 20 minutes - however, during sham stimulation (placebo) the current will not be active for the full 20 minutes.<br>Procedure: transcranial ultrasound<br>* Subjects will undergo 20 minutes of transcranial ultrasound. During active stimulation, the ultrasound will be active for 20 minutes - however, during sham stimulation (placebo) the ultrasound will not be active for the full 20 minutes.<br>|
| Sham Comparator: Sham Electrical Stim/Sham Ultrasound<br>Subjects will undergo sham (placebo) low-intensity transcranial electrical stimulation in conjunction with sham transcranial ultrasound for 20 minutes. | Procedure: low-intensity transcranial electrical stimulation<br>* Subjects will undergo 20 minutes of low-intensity transcranial electrical stimulation of up to 2mA. During active stimulation, the current will be active for 20 minutes - however, during sham stimulation (placebo) the current will not be active for the full 20 minutes.<br>Procedure: transcranial ultrasound<br>* Subjects will undergo 20 minutes of transcranial ultrasound. During active stimulation, the ultrasound will be active for 20 minutes - however, during sham stimulation (placebo) the ultrasound will not be active for the full 20 minutes.<br>|
| Active Comparator: Active Electrical Stim/Sham Ultrasound<br>Subjects will undergo active low-intensity transcranial electrical stimulation in conjunction with sham (placebo) transcranial ultrasound for 20 minutes. | Procedure: low-intensity transcranial electrical stimulation<br>* Subjects will undergo 20 minutes of low-intensity transcranial electrical stimulation of up to 2mA. During active stimulation, the current will be active for 20 minutes - however, during sham stimulation (placebo) the current will not be active for the full 20 minutes.<br>Procedure: transcranial ultrasound<br>* Subjects will undergo 20 minutes of transcranial ultrasound. During active stimulation, the ultrasound will be active for 20 minutes - however, during sham stimulation (placebo) the ultrasound will not be active for the full 20 minutes.<br>|
| Active Comparator: Sham Electrical Stim/Active Ultrasound<br>Subjects will undergo sham (placebo) low-intensity transcranial electrical stimulation in conjunction with active transcranial ultrasound for 20 minutes. | Procedure: low-intensity transcranial electrical stimulation<br>* Subjects will undergo 20 minutes of low-intensity transcranial electrical stimulation of up to 2mA. During active stimulation, the current will be active for 20 minutes - however, during sham stimulation (placebo) the current will not be active for the full 20 minutes.<br>Procedure: transcranial ultrasound<br>* Subjects will undergo 20 minutes of transcranial ultrasound. During active stimulation, the ultrasound will be active for 20 minutes - however, during sham stimulation (placebo) the ultrasound will not be active for the full 20 minutes.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in Motor Function | We will measure motor symptoms using the Unified Parkinson's Disease Rating Scale (UPDRS), bradykinesia tests and walking tests. We will assess the changes in these scales from baseline. | Measured for approximately 2 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety | We will measure safety using a battery of electrophysiology, cognitive and neurological safety markers. We will use the Scales for Outcomes in PD-Cognitive (SCOPA-COg), the n-back working memory test, adverse effects questionnaire, electroencephalography (EEG) and a standardized neurological exam | Measured for approximately 2 months | 
| Neurophysiological Changes | We will also use transcranial magnetic stimulation (TMS) and Doppler Ultrasound to assess electrophysiology and cerebral bloodflow markers. | Measured for approximately 2 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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noninvasive stimulation, motor function, transcranial stimulation, transcranial ultrasound, brain stimulation