Transcranial Direct Current Stimulation and Dual Tasks

Study Overview
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Brief Summary
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The project aims to evaluate the clinical and biological effects on patients with Parkinson's disease of an innovative treatment characterized by the use of transcranial Direct Current Stmulation (tDCs) with Dual Task (DT), i.e. including the performance of motor activities in conjunction with the request of cognitive performance, such as executive functions (creative flexibility, working memory and divided attention). Randomized controlled, double-blind, non-pharmacological study using device.The project involves the enrollment of 30 patients.Participants will be randomized into 2 groups: 15 / group and will carry out activities in DT associated with tDCS real (test group) or sham (control group). Each will carry out 12 rehabilitation sessions (2 / week) of 30 minutes. A follow-up is foreseen for all 12 weeks after the end of the treatment. Patients will undergo, at baseline (T0), at the end of the session (T1) and at 12 weeks (T2), a motor and a cognitive profile, moreover a blood sample will be taken. The project intends to improve the state of Parkinson's patients both thanks to the type of protocol that associates DT and tDCS, and thanks to the verification of the treatment through personalized biological analyzes. In detail, improvement in clinical performance, space-time variables in gait and cognitive tests are expected; the variability of synaptic and pathological markers will serve to verify the effect of the treatment.

Detailed Description
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Parkinson's disease (PD) is a neurodegenerative disease characterized by motor symptoms such as tremor at rest, rigidity, bradykinesia, postural instability and cognitive deficits A growing number of studies show that transcranial direct current electrical stimulation (tDCS), a low-cost, non-invasive brain stimulation method, could potentially become a clinical tool for rehabilitation of patients with Parkinson's disease. Furthermore, some studies have shown that walking deficit in patients with Parkinson's disease is exacerbated by adding a dual cognitive or motor task. Daily activities require walking while simultaneously performing cognitive and / or motor tasks, such as talking to a friend or carrying a glass of water. This is why there are Dual Task (DT) training programs for patients with Parkinson's disease. A recent systematic review and meta-analysis demonstrated that treatment in DT can be an effective method of improving walking in terms of walking speed and cadence, balance and other motor symptoms in patients with Parkinson's disease. Future investigations are needed to determine stimulation characteristics and optimal dosage when combined with training in DT. The present study aims to investigate whether the application of tDCS at the dorso lateral prefrontal cortex(DLPFC) region level can add significant improvements to the motor and cognitive profile in patients with Parkinson's disease. Randomized controlled, double-blind, non-pharmacological study using device. The data will be collected at the Department of Neurorehabilitation Sciences of the Polyclinic Nursing Home in Milan. The project involves the enrollment of 30 patients. Each patient will take part in the study after an overall assessment of the general medical conditions, in relation to the suitability for participation in the study, by the neurologist of the unit department of Neuromotor Rehabilitation. Randomized quadruple-blind study in parallel groups, in which the therapist who will carry out the treatment and the patient will not be aware of the assignment to the group (experimental vs control). Participants will be randomized into 2 groups, using Research Electronic Data Capture (RedCap) software:15 / group and will carry out activities in DT associated with tDCS real (test group) or sham (control group). Each will carry out 12 rehabilitation sessions (2 / week) of 30 minutes. A follow-up is foreseen for all 12 weeks after the end of the treatment. Patients will undergo, at baseline (T0), at the end of the session (T1) and at 12 weeks (T2), a motor and a cognitive profile, moreover a blood sample will be taken. The project intends to improve the state of Parkinson's patients both thanks to the type of protocol that associates DT and tDCS, and thanks to the verification of the treatment through personalized biological analyzes. In detail, improvement in clinical performance, space-time variables in gait and cognitive tests are expected; the variability of synaptic and pathological markers will serve to verify the effect of the treatment.

Official Title
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Transcranial Direct Current Stimulation and Dual Tasks in Parkinson's Disease-tDCS&DT in PD

Conditions
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Parkinson Disease

Intervention / Treatment
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* Device: Transcranial Direct Current Stimulation
* Procedure: Dual task


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Parkinson's disease patient (Hoehn and Yahr I-III); Ability to walk with or without aid for 100 meters, Mini Mental State Examination> 21, Ability to express informed consent Exclusion Criteria: Inability of the patient to understand or perform the task based on the evaluation and judgment of the referring neuropsychologist and the investigator, and / or to sign or initial the informed consent; History of other previous, disabling neurological diseases (e.g., Stroke cerebri, Alzheimer's Disease, Multiple Sclerosis and Disabling Peripheral Neuropathy) and / or ongoing psychiatric diseases (e.g., major depression); Presence of contraindications to stimulation according to the most recent guidelines; Brain metal implants- Pace-makers, brain stimulators, cochlear implants- Pregnancy status (for women); Patient denial of informed consent.

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 85 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: Parallel Assignment
Interventional Model Description: Participants will be randomized into 2 groups, using REDCap (Research Electronic Data Capture) software (Harris et al, 2009): 15 / group and will carry out activities in Dual Task (DT) associated with transcranial Direct Current Stimulation (tDCS) real (test group) or sham (control group).
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: tDCS group<br>transcranial Direct Current Stimulation group (tDCS group) : patients carry out activities in Dual Task associated with tDCS real. | Device: Transcranial Direct Current Stimulation<br>* The stimulator will be connected to two electrodes .The active electrode will be placed on the areas of the dorsal lateral pre-frontal cortex (DLPFC) contralateral to the more affected side.The other one on the supra orbital area.<br>Procedure: Dual task<br>* The Dual Task consists of walking for 20 minutes along a hallway, simultaneously patient has to answer to a different ecological cognitive (attention, fluences, calculation) and motor tasks (hold a tray, turn head, ecc..)<br>|
| Sham Comparator: Sham group<br>Sham group: patients carry out activities in Dual Task associated with tDCS sham. | Device: Transcranial Direct Current Stimulation<br>* The stimulator will be connected to two electrodes .The active electrode will be placed on the areas of the dorsal lateral pre-frontal cortex (DLPFC) contralateral to the more affected side.The other one on the supra orbital area.<br>Procedure: Dual task<br>* The Dual Task consists of walking for 20 minutes along a hallway, simultaneously patient has to answer to a different ecological cognitive (attention, fluences, calculation) and motor tasks (hold a tray, turn head, ecc..)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of duration (seconds) of 10 Meters Walking Test (single and dual task) | Patient has to walk for ten meters with (dual task) or without(single task) a cognitive task | At baseline (t0) after 45 days (t1) and after 84 days (t2) | 
| Change of duration (seconds) of Time Up and Go (single and dual task) | Patient has to sit from a chair, walk for 3 meters, turn and walk back to sit on the chair, with (dual task) or without (single task) a cognitive task. | At baseline (t0) after 45 days (t1) and 84 days (t2) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Unified Parkinson's Disease Rating Scale (UPDRS; part III-motor part) | Assessment on motor performance (balance, walking, manual dexterity) UPDRS, the minimum value is 0,the maximum is 132, higher scores mean worse outcome. | At baseline, after 45 days (t1) and 84 days (t2) | 
| Mini-best test, | Assessment of balance, the minimum value is 0,the maximum is 28, higher scores mean better outcome. | At baseline (t0),after 45 days (t1) and 84 days (t2) | 
| Freezing Of Gait questionnaire (FOG) | Assessment of freezing of gait .The minimum value is 0,the maximum is 24, higher scores mean worse outcome. | At baseline (t0),after 45 days (t1) and 84 days (t2) | 
| Montreal Cognitive Assessment (MoCA; Conti et al., 2015) | Index of global cognitive and executive functioning | At baseline (t0), after 45 days (t1) and 84 days (t2) | 
| Digit Span Forward e Backward (Monaco et al. 2013) | The assessment of short-term and verbal working memory | At baseline (t0),after 45 days (t1) and 84 days (t2) | 
| Wisconsin Card Sorting Test (Laiacona et al., 2000) | To assess planning, flexibility and monitoring skills in a complex problem-solving task | At baseline (t0),after 45 days (t1) and 84 days (t2) | 
| Trail Making Test (TMT; Giovagnoli et al., 1996) | Processing speed index and attentional shifting | At baseline (t0),after 45 days (t1) and 84 days (t2) | 
| Italian version of the Parkinson's Disease-Cognitive Rating Scale (PD-CRS; Santangelo et al., 2014). | Tests for the assessment of immediate verbal memory, visual comparison naming, sustained attention, working memory, clock drawing, deferred verbal memory, alternating fluency, verbal fluency of actions | At baseline (t0),after 45 days (t1) and 84 days (t2) | 
| Biomarkers (Brain Derived Neurotrophic Factor BDNF, dopamine, synaptic proteins, α-synuclein, inflammatory and oxidative stress factors, circRNA, miRNA, with techniques of biochemistry, genetics and immunohistochemistry) | A blood sample will be taken to acquire plasma, serum and exosomes. | At baseline (t0),after 45 days (t1) and 84 days (t2) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Transcranial direct current stimulation, Dual task, Biomarkers, Parkinson