Cerebello-Spinal tDCS as Rehabilitative Intervention in Neurodegenerative Ataxia (SCA02)

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

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.

Study Overview

• Status: Completed
• Conditions: Ataxia; Multiple System Atrophy; Spinocerebellar Ataxias; Spinocerebellar Ataxia 3; Spinocerebellar Ataxia Type 1; Spinocerebellar Ataxia Type 2; Ataxia With Oculomotor Apraxia; CANVAS
• Intervention / Treatment: Device: Anodal cerebellar and cathodal spinal tDCS; Device: Sham cerebellar and sham spinal tDCS

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 61
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Italy
  • BS
    • Brescia, BS, Italy, 25100
      • AO Spedali Civili

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia

Publications and helpful links

General Publications

• Rossini PM, Burke D, Chen R, Cohen LG, Daskalakis Z, Di Iorio R, Di Lazzaro V, Ferreri F, Fitzgerald PB, George MS, Hallett M, Lefaucheur JP, Langguth B, Matsumoto H, Miniussi C, Nitsche MA, Pascual-Leone A, Paulus W, Rossi S, Rothwell JC, Siebner HR, Ugawa Y, Walsh V, Ziemann U. Non-invasive electrical and magnetic stimulation of the brain, spinal cord, roots and peripheral nerves: Basic principles and procedures for routine clinical and research application. An updated report from an I.F.C.N. Committee. Clin Neurophysiol. 2015 Jun;126(6):1071-1107. doi: 10.1016/j.clinph.2015.02.001. Epub 2015 Feb 10.
• Bikson M, Grossman P, Thomas C, Zannou AL, Jiang J, Adnan T, Mourdoukoutas AP, Kronberg G, Truong D, Boggio P, Brunoni AR, Charvet L, Fregni F, Fritsch B, Gillick B, Hamilton RH, Hampstead BM, Jankord R, Kirton A, Knotkova H, Liebetanz D, Liu A, Loo C, Nitsche MA, Reis J, Richardson JD, Rotenberg A, Turkeltaub PE, Woods AJ. Safety of Transcranial Direct Current Stimulation: Evidence Based Update 2016. Brain Stimul. 2016 Sep-Oct;9(5):641-661. doi: 10.1016/j.brs.2016.06.004. Epub 2016 Jun 15.
• Benussi A, Dell'Era V, Cantoni V, Bonetta E, Grasso R, Manenti R, Cotelli M, Padovani A, Borroni B. Cerebello-spinal tDCS in ataxia: A randomized, double-blind, sham-controlled, crossover trial. Neurology. 2018 Sep 18;91(12):e1090-e1101. doi: 10.1212/WNL.0000000000006210. Epub 2018 Aug 22.
• Lefaucheur JP, Antal A, Ayache SS, Benninger DH, Brunelin J, Cogiamanian F, Cotelli M, De Ridder D, Ferrucci R, Langguth B, Marangolo P, Mylius V, Nitsche MA, Padberg F, Palm U, Poulet E, Priori A, Rossi S, Schecklmann M, Vanneste S, Ziemann U, Garcia-Larrea L, Paulus W. Evidence-based guidelines on the therapeutic use of transcranial direct current stimulation (tDCS). Clin Neurophysiol. 2017 Jan;128(1):56-92. doi: 10.1016/j.clinph.2016.10.087. Epub 2016 Oct 29.
• Benussi A, Dell'Era V, Cotelli MS, Turla M, Casali C, Padovani A, Borroni B. Long term clinical and neurophysiological effects of cerebellar transcranial direct current stimulation in patients with neurodegenerative ataxia. Brain Stimul. 2017 Mar-Apr;10(2):242-250. doi: 10.1016/j.brs.2016.11.001. Epub 2016 Nov 3.
• Benussi A, Koch G, Cotelli M, Padovani A, Borroni B. Cerebellar transcranial direct current stimulation in patients with ataxia: A double-blind, randomized, sham-controlled study. Mov Disord. 2015 Oct;30(12):1701-5. doi: 10.1002/mds.26356. Epub 2015 Aug 14.
• Miranda PC, Salvador R, Wenger C, Fernandes SR. Computational models of non-invasive brain and spinal cord stimulation. Annu Int Conf IEEE Eng Med Biol Soc. 2016 Aug;2016:6457-6460. doi: 10.1109/EMBC.2016.7592207.
• Fiocchi S, Ravazzani P, Priori A, Parazzini M. Cerebellar and Spinal Direct Current Stimulation in Children: Computational Modeling of the Induced Electric Field. Front Hum Neurosci. 2016 Oct 17;10:522. doi: 10.3389/fnhum.2016.00522. eCollection 2016.
• van Dun K, Bodranghien F, Manto M, Marien P. Targeting the Cerebellum by Noninvasive Neurostimulation: a Review. Cerebellum. 2017 Jun;16(3):695-741. doi: 10.1007/s12311-016-0840-7.

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2018
• Primary Completion (Actual): December 1, 2020
• Study Completion (Actual): January 1, 2021

Study Registration Dates

• First Submitted: October 29, 2019
• First Submitted That Met QC Criteria: November 4, 2019
• First Posted (Actual): November 6, 2019

Study Record Updates

• Last Update Posted (Actual): March 19, 2021
• Last Update Submitted That Met QC Criteria: March 17, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Keywords: Transcranial magnetic stimulation; Transcranial direct current stimulation; Cerebellar ataxia; Spinocerebellar ataxia
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Eye Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Genetic Diseases, Inborn; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Dyskinesias; Psychomotor Disorders; Vasculitis; Spinal Cord Diseases; Heredodegenerative Disorders, Nervous System; Cranial Nerve Diseases; Autonomic Nervous System Diseases; Primary Dysautonomias; Hypotension; Cerebellar Diseases; Vestibulocochlear Nerve Diseases; Ataxia; Multiple System Atrophy; Shy-Drager Syndrome; Apraxias; Cerebellar Ataxia; Spinocerebellar Ataxias; Spinocerebellar Degenerations; Machado-Joseph Disease; Cogan Syndrome
• Other Study ID Numbers: NP3244

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No