Rehabilitative Trial With Cerebello-Spinal tDCS in Neurodegenerative Ataxia

Study Overview
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Brief Summary
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Neurodegenerative cerebellar ataxias represent a group of disabling disorders for which we currently lack effective therapies. Cerebellar transcranial direct current stimulation (tDCS) is a non-invasive technique, which has been demonstrated to modulate cerebellar excitability and improve symptoms in patients with cerebellar ataxias. In this randomized, double-blind, sham-controlled study, the investigators will evaluate whether a two-weeks' treatment with cerebellar anodal tDCS and spinal cathodal tDCS can improve symptoms in patients with neurodegenerative cerebellar ataxia and can modulate cerebello-motor connectivity, at short and long term.

Detailed Description
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Neurodegenerative cerebellar ataxias represent a heterogeneous group of disabling disorders in which progressive ataxia of gait, limb dysmetria, oculomotor deficits, dysarthria and kinetic tremor are the prominent clinical manifestations. Both the hereditary and sporadic forms usually present in young adulthood, and are characterized by atrophy of cerebellar or brainstem structures. Currently, cerebellar ataxia lack effective disease-modifying therapies. Cerebellar transcranial direct current stimulation (tDCS) is a non-invasive technique, which has been demonstrated to modulate cerebellar excitability and improve symptoms in patients with cerebellar ataxias. The present randomized, double-blind, sham-controlled study will investigate whether a two-weeks' treatment with cerebellar anodal tDCS and spinal cathodal tDCS can improve symptoms in patients with neurodegenerative cerebellar ataxia and can modulate cerebello-motor connectivity, at short and long term. Subjects will be randomized in two groups, one receiving a 10 day (5 days/week for 2 weeks) treatment with anodal cerebellar and cathodal spinal tDCS and the other receiving sham stimulation with identical parameters. After the intervention, patients will be reassessed with a clinical and neurophysiological evaluation at 2 weeks, 1 months and 3 month after treatment.

Official Title
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Rehabilitative Trial With Cerebello-Spinal tDCS for the Treatment of Neurodegenerative Ataxia

Conditions
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Ataxia, Cerebellar, Cerebellar Ataxia, Spinocerebellar Ataxias, Ataxia, Spinocerebellar, Spinocerebellar Ataxia Type 1, Spinocerebellar Ataxia Type 2, Spinocerebellar Ataxia 3, Spinocerebellar Degenerations, Friedreich Ataxia, Ataxia With Oculomotor Apraxia, Multiple System Atrophy

Intervention / Treatment
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* Device: Anodal cerebellar and cathodal spinal tDCS
* Device: Sham cerebellar and sham spinal tDCS


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with a cerebellar syndrome and quantifiable cerebellar atrophy Exclusion Criteria: Severe head trauma in the past History of seizures History of ischemic stroke or hemorrhage Pacemaker Metal implants in the head/neck region Severe comorbidity Intake of illegal drugs Pregnancy

Ages Eligible for Study
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Minimum Age: 18 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: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Real tDCS<br>10 days anodal cerebellar and cathodal spinal tDCS | Device: Anodal cerebellar and cathodal spinal tDCS<br>* 10 sessions of anodal cerebellar and cathodal spinal transcranial direct current stimulation (5 days/week for 2 weeks)<br>|
| Sham Comparator: Sham tDCS<br>10 days sham cerebellar and sham spinal tDCS | Device: Sham cerebellar and sham spinal tDCS<br>* 10 sessions of sham cerebellar and sham spinal transcranial direct current stimulation (5 days/week for 2 weeks)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the International Cooperative Ataxia Rating Scale (ICARS) Score From Baseline | International Cooperative Ataxia Rating Scale (ICARS): semi-quantitative 100-point scale, yielding a total score of 0 (no ataxia) to 100 (most severe ataxia). | Baseline - 2 weeks | 
| Change in the Scale for the Assessment and Rating of Ataxia (SARA) Score From Baseline | Scale for the Assessment and Rating of Ataxia (SARA): 8-item performance based scale, yielding a total score of 0 (no ataxia) to 40 (most severe ataxia). | Baseline - 2 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the International Cooperative Ataxia Rating Scale (ICARS) Score From Baseline | International Cooperative Ataxia Rating Scale (ICARS): semi-quantitative 100-point scale, yielding a total score of 0 (no ataxia) to 100 (most severe ataxia). | Baseline - 2 weeks - 1 month - 3 months | 
| Change in the Scale for the Assessment and Rating of Ataxia (SARA) Score From Baseline | Scale for the Assessment and Rating of Ataxia (SARA): 8-item performance based scale, yielding a total score of 0 (no ataxia) to 40 (most severe ataxia). | Baseline - 2 weeks - 1 month - 3 months | 
| Change in the 9 Hole Peg Test (9HPT) Score From Baseline | 4 timed trials of the 9 hole peg test (9HPT) were performed and averaged (mean values are reported) for each separate hand (dominant and nondominant). The total time to complete the task is recorded for each trial and for each separate hand (dominant and nondominant). Longer times represent greater impairment. | Baseline - 2 weeks - 1 month - 3 months | 
| Change in the 8-Meter Walking Time (8MW) Score From Baseline | 4 timed trials of the 8 meter walking time (8MW) were performed and averaged (mean values are reported). Longer times represent greater impairment. | Baseline - 2 weeks - 1 month - 3 months | 
| Change in Cerebellar Brain Inhibition (CBI) Measurements From Baseline | Cerebellar brain inhibition (CBI) is expressed as motor evoked potential amplitude (average of 10 recordings). Lower values reflect higher inhibition and thus reduced impairment. | Baseline - 2 weeks - 1 month - 3 months | 
| Change in the Short-Form Health Survey 36 (SF36) Score From Baseline | The Italian version of the Short-Form Health Survey 36 (SF-36): consists of 36 scaled score, yielding a total score of 0 (more disability) to 100 (less disability). | Baseline - 2 weeks - 1 month - 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cerebellar ataxia, Transcranial direct current stimulation, Transcranial magnetic stimulation, Spinocerebellar ataxia