Cerebello-Spinal tDCS as Rehabilitative Intervention in Neurodegenerative Ataxia

Multiple System Atrophy Clinical Trial

— SCA02  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04153110
• Other study ID #: NP3244
• Status: Completed
• Phase: N/A
• Start date: December 1, 2018
• Est. completion date: January 1, 2021

Study information

• Verified date: March 2021
• Source: Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 61
• Est. completion date: January 1, 2021
• Est. primary completion date: December 1, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Apraxias
• Ataxia
• Ataxia With Oculomotor Apraxia
• CANVAS
• Cerebellar Ataxia
• Machado-Joseph Disease
• Multiple System Atrophy
• Shy-Drager Syndrome
• Spinocerebellar Ataxia 3
• Spinocerebellar Ataxia Type 1
• Spinocerebellar Ataxia Type 2
• Spinocerebellar Ataxias
• Spinocerebellar Degenerations

Intervention

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 cerebellar and sham spinal tDCS
10 sessions of sham cerebellar and sham spinal transcranial direct current stimulation (5 days/week for 2 weeks)

Locations

Country	Name	City	State
Italy	AO Spedali Civili	Brescia	BS

Sponsors (1)

Lead Sponsor	Collaborator
Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia

Country where clinical trial is conducted

Italy, 

References & Publications (9)

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. — View Citation

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. — View Citation

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. — View Citation

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. Review. — View Citation

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. eCollection 2016. — View Citation

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. Review. — View Citation

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. — View Citation

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. Review. — View Citation

van Dun K, Bodranghien F, Manto M, Mariën P. Targeting the Cerebellum by Noninvasive Neurostimulation: a Review. Cerebellum. 2017 Jun;16(3):695-741. doi: 10.1007/s12311-016-0840-7. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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