Multimodal Neuromodulation in Individuals With Parkinson's Disease

Study Overview
=================
Brief Summary
-----------------
Multimodal non-invasive neuromodulation paired with physical therapy is a promising treatment modality for Parkinson's Disease (PD), however the optimal stimulation method, dose, and associated therapeutic protocol for long-lasting clinical benefits have not yet been identified for this population. Here the investigators aim to develop and execute a preliminary clinical study exploring the potential benefits of multimodal non-invasive neuromodulation. The therapeutic intervention will involve translingual neurostimulation +/- galvanic neurostimulation, paired with an intensive physical and cognitive therapy program.

Official Title
-----------------
Multimodal Neuromodulation in Individuals With Parkinson's Disease

Conditions
-----------------
Parkinson Disease

Intervention / Treatment
-----------------
* Device: Galvanic stimulation


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: A diagnosis of idiopathic PD Disease staging between II and III (mild to moderate), according to the modified Hoehn and Yahr scale; Currently taking prescribed antiparkinsonian medication regularly with: No medication changes in the last 30 days Responsive to oral dopamine replacement therapy Score higher than 24, verified through the Montreal Cognitive Assessment33. Must demonstrate moderate burden of motor symptoms (MDS-UPDRS part II >12 and MDS-UPDRS part III scores >35) 34 Must be able to voluntarily give written (or verbal) informed consent Must have ability to reliably use the devices Must be able to understand and complete all assessments (provided in English only) Exclusion Criteria: Diagnosis of atypical parkinsonism; History of epilepsy Presence of an implanted electrical device Previous surgical intervention for PD (DBS implantation - deep brain stimulation); Treated with a pump for continuous delivery of DRT (Dopamine replacement therapy) Presence of severe freezing episodes. Women who are pregnant or nursing History of unstable mood disorder or unstable anxiety disorder or psychosis Those with a recent history of substance abuse and/or dependence (alcohol or other drugs) Have been diagnosed with neurological disease other than Parkinson's disease. Have a major concomitant illness or illnesses including cancer or disease of the cardiovascular, respiratory and/or renal systems deemed significant medical risk in the opinion of the principle investigator Have a diagnosed vestibular dysfunction Have had eye surgery within the previous three months or ear surgery within the previous six months Have participated in another clinical trial within the last 30 days or are currently enrolled in another interventional clinical trial Contraindicated for PoNS, including: 25.1. Current disease or sensitivity of the oral cavity 25.2. History of oral cancer 25.3. Oral surgery within three months of screening 25.4. Oral cavity piercings that could interfere with PoNSTM use 25.5. Sensitivity to Nickel, Copper, or Gold 25.6. Currently enrolled in a PoNSTM treatment program or use of the PoNSTM device in the last 5 weeks 25.7. History of penetrating brain injuries 25.8. Chronic infectious disease 25.9. Unmanaged hypertension 25.10. Diabetes 25.11. History of seizures Contraindicated for GVS, including: 26.1. Metallic brain implant(s) 26.2. Brain surgery within the past six months 26.3. Highly sensitive skin behind the ears
Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Physiotherapy only<br> | |
| Experimental: Active galvanic stimulation (GVS; week 1) to sham GVS (week 2)<br>Physiotherapy + translingual neurostimulation provided throughout | Device: Galvanic stimulation<br>* Galvanic stimulation during physiotherapy sessions<br>|
| Experimental: Sham GVS (week 1) to active GVS (week 2)<br>Physiotherapy + translingual neurostimulation provided throughout | Device: Galvanic stimulation<br>* Galvanic stimulation during physiotherapy sessions<br>|
| Experimental: Active GVS throughout weeks 1 + 2<br>Physiotherapy + translingual neurostimulation provided throughout | Device: Galvanic stimulation<br>* Galvanic stimulation during physiotherapy sessions<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| NeuroCom Sensory Organization Test (SOT) | Composite balance score | Baseline to week 4 | 
| NeuroCom Limits of Stability test (LOS) | Postural stability score | Baseline to week 4 | 
| NeuroCom Adaptation Test | Adaptation score | Baseline to week 4 | 
| MiniBESTest | Balance score | Baseline to week 4 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Electroencephalography - amplitudes | Measured with NeuroCatch Platform 2 (NCP) | Baseline to week 4 | 
| Electroencephalography - latencies | Measured with NeuroCatch Platform 2 (NCP) | Baseline to week 4 | 
| Unified Parkinson's Disease Rating Scale | Part II and part III: Motor function score | Baseline to week 4 | 
| Montreal Cognitive Assessment (MoCA) | Cognitive test; total score | Baseline to week 4 |