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CompletedNCT03120013CStDCSAtaxiaUpdated Mar 3, 2020Results posted

Rehabilitative Trial With Cerebello-Spinal tDCS in Neurodegenerative Ataxia

An interventional study of Anodal cerebellar and cathodal spinal tDCS and Sham cerebellar and sham spinal tDCS in Ataxia, Cerebellar, Cerebellar Ataxia and Spinocerebellar Ataxias, sponsored by Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia. Completed at 1 site in Italy. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2020-03-03.

Sponsored by Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia · Not applicable, Interventional, and Treatment

Phase
Not applicable
Study type
Interventional
Enrollment
21
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study 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.

Read the 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.

02

Conditions studied

  • 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

Keywords

  • Transcranial direct current stimulation
  • Transcranial magnetic stimulation
  • Spinocerebellar ataxia
  • Cerebellar ataxia
03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • Patients with a cerebellar syndrome and quantifiable cerebellar atrophy

Exclusion criteria

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
04

Study design

Phase
Not applicable
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Crossover assignment
Masking
Triple (Participant, Care provider, Investigator)
Enrollment
21 participants (actual)

Study arms

  • Experimental
    Real tDCS

    10 days anodal cerebellar and cathodal spinal tDCS

    Device: Anodal cerebellar and cathodal spinal tDCS

  • Sham comparator
    Sham tDCS

    10 days sham cerebellar and sham spinal tDCS

    Device: Sham cerebellar and sham spinal tDCS

Interventions

  • DeviceAnodal cerebellar and cathodal spinal tDCS

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

  • DeviceSham cerebellar and sham spinal tDCS

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

05

What researchers measure

Primary outcomes

  1. 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).

    Time frame: Baseline - 2 weeks

  2. 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).

    Time frame: Baseline - 2 weeks

Secondary outcomes

  1. 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).

    Time frame: Baseline - 2 weeks - 1 month - 3 months

  2. 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).

    Time frame: Baseline - 2 weeks - 1 month - 3 months

  3. Change in the 9 Hole Peg Test (9HPT) Score From Baseline

    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.

    Time frame: Baseline - 2 weeks - 1 month - 3 months

  4. Change in the 8-Meter Walking Time (8MW) Score From Baseline

    4 timed trials of the 8 meter walking time (8MW) were performed and averaged (mean values are reported). Longer times represent greater impairment.

    Time frame: Baseline - 2 weeks - 1 month - 3 months

  5. 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.

    Time frame: Baseline - 2 weeks - 1 month - 3 months

  6. 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).

    Time frame: Baseline - 2 weeks - 1 month - 3 months

06

Results

Posted Jun 28, 2019

Participant flow

First Intervention (2 Weeks)
Participant flow — First Intervention (2 Weeks)
MilestoneReal tDCS, Then Sham tDCSSham tDCS, Then Real tDCS
Started1011
Received intervention1011
Completed1010
Not completed01
Withdrew: Withdrawal by subject01
Washout (6 Months)
Participant flow — Washout (6 Months)
MilestoneReal tDCS, Then Sham tDCSSham tDCS, Then Real tDCS
Started1010
Completed1010
Not completed00
Second Intervention (2 Weeks)
Participant flow — Second Intervention (2 Weeks)
MilestoneReal tDCS, Then Sham tDCSSham tDCS, Then Real tDCS
Started1010
Completed1010
Not completed00

Outcome measures

PrimaryChange 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).

Time frame:
Baseline - 2 weeks
Reported as:
Mean · units on a scale
Change in the International Cooperative Ataxia Rating Scale (ICARS) Score From Baseline
units on a scaleReal tDCSSham tDCS
Baseline53.0 ± 18.652.7 ± 19.4
2 Weeks43.0 ± 19.652.1 ± 19.7
Statistical analysis
  • Real tDCS vs Sham tDCS · ANCOVA · p = <0.001
PrimaryChange 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).

Time frame:
Baseline - 2 weeks
Reported as:
Mean · units on a scale
Change in the Scale for the Assessment and Rating of Ataxia (SARA) Score From Baseline
units on a scaleReal tDCSSham tDCS
Change in the Scale for the Assessment and Rating of Ataxia (SARA) Score From Baseline15.8 ± 7.619.7 ± 7.5
Statistical analysis
  • Real tDCS vs Sham tDCS · ANCOVA · p = <0.001
SecondaryChange 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).

Time frame:
Baseline - 2 weeks - 1 month - 3 months
Reported as:
Mean · units on a scale
Change in the International Cooperative Ataxia Rating Scale (ICARS) Score From Baseline
units on a scaleReal tDCSSham tDCS
Baseline53.0 ± 18.652.7 ± 19.4
2 Weeks43.0 ± 19.652.1 ± 19.7
1 Month41.3 ± 19.652.5 ± 19.2
3 Months44.2 ± 19.652.4 ± 19.4
Statistical analysis
  • Real tDCS vs Sham tDCS · ANCOVA · p = <0.001
SecondaryChange 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).

Time frame:
Baseline - 2 weeks - 1 month - 3 months
Reported as:
Mean · units on a scale
Change in the Scale for the Assessment and Rating of Ataxia (SARA) Score From Baseline
units on a scaleReal tDCSSham tDCS
Baseline20.2 ± 7.319.9 ± 7.3
2 Weeks15.8 ± 7.619.7 ± 7.5
1 Month15.1 ± 7.719.7 ± 7.3
3 Months16.1 ± 7.919.9 ± 7.6
Statistical analysis
  • Real tDCS vs Sham tDCS · ANCOVA · p = <0.001
SecondaryChange in the 9 Hole Peg Test (9HPT) Score From Baseline

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.

Time frame:
Baseline - 2 weeks - 1 month - 3 months
Reported as:
Mean · seconds
Change in the 9 Hole Peg Test (9HPT) Score From Baseline
secondsReal tDCSSham tDCS
Baseline53.0 ± 24.352.2 ± 25.9
2 Weeks46.2 ± 21.353.4 ± 23.8
1 Month47.1 ± 21.955.8 ± 28.1
3 Months49.5 ± 20.554.2 ± 26.2
Statistical analysis
  • Real tDCS vs Sham tDCS · ANCOVA · p = <0.001
SecondaryChange in the 8-Meter Walking Time (8MW) Score From Baseline

4 timed trials of the 8 meter walking time (8MW) were performed and averaged (mean values are reported). Longer times represent greater impairment.

Time frame:
Baseline - 2 weeks - 1 month - 3 months
Reported as:
Mean · seconds
Change in the 8-Meter Walking Time (8MW) Score From Baseline
secondsReal tDCSSham tDCS
Baseline9.4 ± 3.49.3 ± 3.3
2 Weeks8.0 ± 2.79.0 ± 3.9
1 Month7.8 ± 2.79.9 ± 5.0
3 Months8.4 ± 2.89.7 ± 4.1
Statistical analysis
  • Real tDCS vs Sham tDCS · ANCOVA · p = =0.006
SecondaryChange 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.

Time frame:
Baseline - 2 weeks - 1 month - 3 months
Reported as:
Mean · millivolts
Change in Cerebellar Brain Inhibition (CBI) Measurements From Baseline
millivoltsReal tDCSSham tDCS
Baseline0.94 ± 0.120.88 ± 0.12
2 Weeks0.54 ± 0.130.91 ± 0.12
1 Month0.65 ± 0.140.95 ± 0.13
3 Months0.74 ± 0.110.90 ± 0.12
Statistical analysis
  • Real tDCS vs Sham tDCS · ANCOVA · p = <0.001
SecondaryChange 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).

Time frame:
Baseline - 2 weeks - 1 month - 3 months
Reported as:
Mean · units on a scale
Change in the Short-Form Health Survey 36 (SF36) Score From Baseline
units on a scaleReal tDCSSham tDCS
Baseline54.7 ± 17.555.3 ± 19.5
2 Weeks66.5 ± 17.557.9 ± 18.5
1 Month66.7 ± 16.860.1 ± 17.8
3 Months61.1 ± 18.856.3 ± 18.8
Statistical analysis
  • Real tDCS vs Sham tDCS · ANCOVA · p = =0.043

Adverse events

Collected over 9 months. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Real tDCS, Then Sham tDCS0/10 (0%)0/10 (0%)0/10 (0%)
Sham tDCS, Then Real tDCS0/11 (0%)0/11 (0%)0/11 (0%)

Baseline characteristics

Baseline analysis are reported for 20 participants who completed the first intervention

Age, Continuous
Age, Continuous(years)All Study Participants
Mean54.6 ± 14.5
Sex: Female, Male
Sex: Female, Male(Participants)All Study Participants
Female10
Male10
Race (NIH/OMB)
Race (NIH/OMB)(Participants)All Study Participants
American Indian or Alaska Native0
Asian0
Native Hawaiian or Other Pacific Islander0
Black or African American0
White20
More than one race0
Unknown or Not Reported0
Region of Enrollment
Region of Enrollment(participants)All Study Participants
Italy20
Scale for the Assessment and Rating of Ataxia (SARA) score
Scale for the Assessment and Rating of Ataxia (SARA) score(units on a scale)All Study Participants
Mean20.2 ± 7.4
International Cooperative Ataxia Rating Scale (ICARS) score
International Cooperative Ataxia Rating Scale (ICARS) score(units on a scale)All Study Participants
Mean53.0 ± 18.6
9 Hole Peg Test (Dominant hand)
9 Hole Peg Test (Dominant hand)(seconds)All Study Participants
Mean53.0 ± 24.3
9 Hole Peg Test (non-Dominant hand)
9 Hole Peg Test (non-Dominant hand)(seconds)All Study Participants
Mean56.1 ± 21.5

3 further baseline measures are reported on the registry.

07

Study locations

1 site
  • AO Spedali Civili
    Brescia, BS 25100, Italy
08

References and documents

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. PubMed 26274840 ↗
  • 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. PubMed 27838276 ↗
  • 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. PubMed 27372845 ↗
  • 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. PubMed 25797650 ↗
  • 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. PubMed 28269725 ↗
  • 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. PubMed 27866120 ↗
  • 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. PubMed 27799905 ↗
  • 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. PubMed 28032321 ↗
  • 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. PubMed 30135258 ↗

Study documents

  • Protocol and statistical analysis plan · Jan 21, 2016

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No

09

Registry details

Key details

Study ID
NCT03120013
Lead sponsor
Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia
Responsible party
Barbara Borroni (Professor, Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia) — Principal investigator
First posted
Apr 19, 2017
Start date
Feb 6, 2017
Primary completion
Dec 1, 2018
Completion
Dec 1, 2018
Results posted
Jun 28, 2019
Last update
Mar 3, 2020

Study contacts

Barbara Borroni, MD
principal investigator · Azienda Ospedaliera Spedali Civili, Brescia
Alberto Benussi, MD
principal investigator · Università degli Studi di Brescia

Oversight

Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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