Cerebello-Spinal tDCS as Rehabilitative Intervention in Neurodegenerative Ataxia

Study Overview
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Brief Summary
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Neurodegenerative cerebellar ataxias represent a group of disabling disorders which 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 followed by an open-label phase, the investigators will evaluate whether a repetition of two-weeks' treatment with cerebellar anodal tDCS and spinal cathodal tDCS, after a three months interval, may further outlast clinical improvement 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 followed by an open-label phase will investigate a repetition of two-weeks' treatment with cerebellar anodal tDCS and spinal cathodal tDCS, after a three months interval, may further outlast clinical improvement in patients with neurodegenerative cerebellar ataxia and can modulate cerebello-motor connectivity, at short and long term. In addition the investigators will evaluate if tDCS intervention might improve cerebellar cognitive-affective syndrome in patients with ataxia.

Official Title
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Cerebello-Spinal tDCS as Rehabilitative Intervention in Neurodegenerative Ataxias: a Randomized, Double-blind, Sham-controlled Trial Followed by an Open-label Phase

Conditions
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Ataxia, Spinocerebellar Ataxias, Spinocerebellar Ataxia Type 1, Spinocerebellar Ataxia Type 2, Spinocerebellar Ataxia 3, Multiple System Atrophy, Ataxia With Oculomotor Apraxia, CANVAS

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: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Real tDCS - Real tDCS<br>10 sessions of anodal cerebellar and cathodal spinal transcranial direct current stimulation (5 days/week for 2 weeks) followed by an open-label 10 sessions of anodal cerebellar and cathodal spinal transcranial direct current stimulation (5 days/week for 2 weeks) | 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 - Real tDCS<br>10 sessions of sham cerebellar and sham spinal transcranial direct current stimulation (5 days/week for 2 weeks) followed by an open-label 10 sessions of anodal cerebellar and cathodal spinal transcranial direct current stimulation (5 days/week for 2 weeks). | 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>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 | 
| Change in the Cerebellar cognitive affective syndrome (CCAS) Scale From Baseline | CCAS/Schmahmann syndrome scale: 120 point scale, yielding a total score of 0 (most severe cognitive impairment) to 120 (no cognitive impairment). | 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 - 3 month - 6 months - 9 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 - 3 month - 6 months - 9 months | 
| Change in the Cerebellar cognitive affective syndrome (CCAS) Scale From Baseline | CCAS/Schmahmann syndrome scale: 120 point scale, yielding a total score of 0 (most severe cognitive impairment) to 120 (no cognitive impairment). | Baseline - 2 weeks - 3 month - 6 months - 9 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 - 3 month - 6 months - 9 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 - 3 month - 6 months - 9 months | 

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