Cerebello-Spinal tDCS as Rehabilitative Intervention in Neurodegenerative Ataxia

NCT04153110 | Completed DMC

• 1 other identifier: NP3244
• Study Type: interventional
• Target: 61
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

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

Keywords

Transcranial direct current stimulation; Transcranial magnetic stimulation; Spinocerebellar ataxia; Cerebellar ataxia

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (5)

• Change in the International Cooperative Ataxia Rating Scale (ICARS) Score From Baseline

  Baseline - 2 weeks - 3 month - 6 months - 9 months

• Change in the Scale for the Assessment and Rating of Ataxia (SARA) Score From Baseline

  Baseline - 2 weeks - 3 month - 6 months - 9 months

• Change in the Cerebellar cognitive affective syndrome (CCAS) Scale From Baseline

  Baseline - 2 weeks - 3 month - 6 months - 9 months

• Change in Cerebellar Brain Inhibition (CBI) Measurements From Baseline

  Baseline - 2 weeks - 3 month - 6 months - 9 months

• Change in the Short-Form Health Survey 36 (SF36) Score From Baseline

  Baseline - 2 weeks - 3 month - 6 months - 9 months

Study Arms (2)

Real tDCS - Real tDCS

EXPERIMENTAL

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

Sham tDCS - Real tDCS

SHAM COMPARATOR

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; Device: Sham cerebellar and sham spinal tDCS

Interventions

Anodal cerebellar and cathodal spinal tDCS DEVICE

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

Real tDCS - Real tDCS; Sham tDCS - Real tDCS

Sham cerebellar and sham spinal tDCS DEVICE

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

Sham tDCS - Real tDCS

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with a cerebellar syndrome and quantifiable cerebellar atrophy

You may not qualify if:

• 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

Sponsors & Collaborators

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

Study Sites (1)

AO Spedali Civili

Brescia, BS, 25100, Italy

Location

Related 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.

  PMID: 30135258 BACKGROUND

• 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.

  PMID: 27838276 BACKGROUND

• 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.

  PMID: 26274840 BACKGROUND

• 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.

  PMID: 27372845 BACKGROUND

• 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.

  PMID: 25797650 BACKGROUND

• 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.

  PMID: 28269725 BACKGROUND

• 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.

  PMID: 27866120 BACKGROUND

• 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.

  PMID: 27799905 BACKGROUND

• 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.

  PMID: 28032321 BACKGROUND

MeSH Terms

Conditions

Ataxia; Spinocerebellar Ataxias; Machado-Joseph Disease; Multiple System Atrophy; Spinocerebellar ataxia, autosomal recessive 1; Cerebellar Ataxia

Condition Hierarchy (Ancestors)

Dyskinesias; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Cerebellar Diseases; Brain Diseases; Central Nervous System Diseases; Spinocerebellar Degenerations; Spinal Cord Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Primary Dysautonomias; Autonomic Nervous System Diseases; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies

Study Officials

• Barbara Borroni, MD

  Azienda Ospedaliera Spedali Civili, Brescia

  PRINCIPAL INVESTIGATOR

• Alberto Benussi, MD

  Università degli Studi di Brescia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: October 29, 2019
• First Posted: November 6, 2019
• Study Start: December 1, 2018
• Primary Completion: December 1, 2020
• Study Completion: January 1, 2021
• Last Updated: March 19, 2021

Record last verified: 2021-03

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)