Rehabilitative Trial With Cerebello-Spinal tDCS in Neurodegenerative Ataxia (CStDCSAtaxia)

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ClinicalTrials.gov Identifier: NCT03120013

Recruitment Status : Completed

First Posted : April 19, 2017

Results First Posted : June 28, 2019

Last Update Posted : March 3, 2020

View this study on Beta.ClinicalTrials.gov

Sponsor:

Information provided by (Responsible Party):

Barbara Borroni, Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
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	Device: Anodal cerebellar and cathodal spinal tDCS Device: Sham cerebellar and sham spinal tDCS	Not Applicable

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 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.

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	21 participants
Allocation:	Randomized
Intervention Model:	Crossover Assignment
Masking:	Triple (Participant, Care Provider, Investigator)
Primary Purpose:	Treatment
Official Title:	Rehabilitative Trial With Cerebello-Spinal tDCS for the Treatment of Neurodegenerative Ataxia
Actual Study Start Date :	February 6, 2017
Actual Primary Completion Date :	December 1, 2018
Actual Study Completion Date :	December 1, 2018

Resource links provided by the National Library of Medicine

MedlinePlus Genetics related topics: Infantile-onset spinocerebellar ataxia Multiple system atrophy VLDLR-associated cerebellar hypoplasia Spinocerebellar ataxia type 3 Spinocerebellar ataxia type 2 Spinocerebellar ataxia type 1 Spinocerebellar ataxia type 6 Autosomal recessive cerebellar ataxia type 1 Ataxia with oculomotor apraxia

Genetic and Rare Diseases Information Center resources: Multiple System Atrophy Apraxia Spinocerebellar Ataxia Cogan's Syndrome Ataxia With Oculomotor Apraxia Type 2 Friedreich Ataxia Spinocerebellar Ataxia 3 Spinocerebellar Ataxia 2 Spinocerebellar Ataxia 1

U.S. FDA Resources

Arms and Interventions

Arm	Intervention/treatment
Experimental: Real tDCS 10 days anodal cerebellar and cathodal spinal tDCS	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 10 days sham cerebellar and sham spinal tDCS	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)

Outcome Measures

Primary Outcome Measures :

Change in the International Cooperative Ataxia Rating Scale (ICARS) Score From Baseline [ Time Frame: Baseline - 2 weeks ]
International Cooperative Ataxia Rating Scale (ICARS): semi-quantitative 100-point scale, yielding a total score of 0 (no ataxia) to 100 (most severe ataxia).
Change in the Scale for the Assessment and Rating of Ataxia (SARA) Score From Baseline [ Time Frame: Baseline - 2 weeks ]
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).

Secondary Outcome Measures :

Change in the International Cooperative Ataxia Rating Scale (ICARS) Score From Baseline [ Time Frame: Baseline - 2 weeks - 1 month - 3 months ]
International Cooperative Ataxia Rating Scale (ICARS): semi-quantitative 100-point scale, yielding a total score of 0 (no ataxia) to 100 (most severe ataxia).
Change in the Scale for the Assessment and Rating of Ataxia (SARA) Score From Baseline [ Time Frame: Baseline - 2 weeks - 1 month - 3 months ]
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).
Change in the 9 Hole Peg Test (9HPT) Score From Baseline [ Time Frame: Baseline - 2 weeks - 1 month - 3 months ]
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.
Change in the 8-Meter Walking Time (8MW) Score From Baseline [ Time Frame: Baseline - 2 weeks - 1 month - 3 months ]
4 timed trials of the 8 meter walking time (8MW) were performed and averaged (mean values are reported). Longer times represent greater impairment.
Change in Cerebellar Brain Inhibition (CBI) Measurements From Baseline [ Time Frame: Baseline - 2 weeks - 1 month - 3 months ]
Cerebellar brain inhibition (CBI) is expressed as motor evoked potential amplitude (average of 10 recordings). Lower values reflect higher inhibition and thus reduced impairment.
Change in the Short-Form Health Survey 36 (SF36) Score From Baseline [ Time Frame: Baseline - 2 weeks - 1 month - 3 months ]
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).

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:	18 Years and older (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03120013

Locations

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Italy
AO Spedali Civili
Brescia, BS, Italy, 25100

Sponsors and Collaborators

Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia

Investigators

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Principal Investigator:	Barbara Borroni, MD	Azienda Ospedaliera Spedali Civili, Brescia
Principal Investigator:	Alberto Benussi, MD	Università degli Studi di Brescia

Study Documents (Full-Text)

Documents provided by Barbara Borroni, Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia:

Study Protocol and Statistical Analysis Plan [PDF] January 21, 2016

More Information

Publications of Results:

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.

Other Publications:

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.

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.

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.

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.

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.

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.

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.

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Responsible Party:	Barbara Borroni, Professor, Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia
ClinicalTrials.gov Identifier:	NCT03120013
Other Study ID Numbers:	NP1576
First Posted:	April 19, 2017 Key Record Dates
Results First Posted:	June 28, 2019
Last Update Posted:	March 3, 2020
Last Verified:	March 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	No

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Studies a U.S. FDA-regulated Drug Product:	No
Studies a U.S. FDA-regulated Device Product:	No
Product Manufactured in and Exported from the U.S.:	No

Keywords provided by Barbara Borroni, Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia:


Transcranial direct current stimulation Transcranial magnetic stimulation Spinocerebellar ataxia Cerebellar ataxia

Additional relevant MeSH terms:

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Ataxia Cerebellar Ataxia Multiple System Atrophy Shy-Drager Syndrome Spinocerebellar Ataxias Spinocerebellar Degenerations Friedreich Ataxia Apraxias Machado-Joseph Disease Cogan Syndrome Dyskinesias Neurologic Manifestations Nervous System Diseases Cerebellar Diseases Brain Diseases	Central Nervous System Diseases Primary Dysautonomias Autonomic Nervous System Diseases Basal Ganglia Diseases Movement Disorders Synucleinopathies Neurodegenerative Diseases Hypotension Vascular Diseases Cardiovascular Diseases Spinal Cord Diseases Heredodegenerative Disorders, Nervous System Genetic Diseases, Inborn Mitochondrial Diseases Metabolic Diseases

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