Rehabilitative Trial With Cerebello-Spinal tDCS in Neurodegenerative Ataxia

Rehabilitative Trial With Cerebello-Spinal tDCS for the Treatment of Neurodegenerative Ataxia

Status

Completed

Phases

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT03120013

Acronym

CStDCSAtaxia

Enrollment

Registered

2017-04-19

Start date

2017-02-06

Completion date

2018-12-01

Last updated

2020-03-03

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Ataxia, Cerebellar, Ataxia, Spinocerebellar, Ataxia With Oculomotor Apraxia, Cerebellar Ataxia, Friedreich Ataxia, Multiple System Atrophy, Spinocerebellar Ataxia 3, Spinocerebellar Ataxias, Spinocerebellar Ataxia Type 1, Spinocerebellar Ataxia Type 2, Spinocerebellar Degenerations

Keywords

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

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.

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.

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)

Study design

Allocation

RANDOMIZED

Intervention model

CROSSOVER

Primary purpose

TREATMENT

Masking

TRIPLE (Subject, Caregiver, Investigator)

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

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

Design outcomes

Primary

Measure	Time frame	Description
Change in the International Cooperative Ataxia Rating Scale (ICARS) Score From Baseline	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	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

Measure	Time frame	Description
Change in the 9 Hole Peg Test (9HPT) Score From Baseline	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	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 the International Cooperative Ataxia Rating Scale (ICARS) Score From Baseline	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 Short-Form Health Survey 36 (SF36) Score From Baseline	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).
Change in Cerebellar Brain Inhibition (CBI) Measurements From Baseline	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 Scale for the Assessment and Rating of Ataxia (SARA) Score From Baseline	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).

Countries

Italy

Participant flow

Participants by arm

Arm	Count
All Study Participants Participants who were randomized to receive either real tDCS or sham tDCS	20
Total	20

Withdrawals & dropouts

Period	Reason	FG000	FG001
First Intervention (2 Weeks)	Withdrawal by Subject	0	1

Baseline characteristics

Characteristic	All Study Participants
8 Meter Walking Time	9.4 seconds STANDARD_DEVIATION 3.4
9 Hole Peg Test (Dominant hand)	53.0 seconds STANDARD_DEVIATION 24.3
9 Hole Peg Test (non-Dominant hand)	56.1 seconds STANDARD_DEVIATION 21.5
Age, Continuous	54.6 years STANDARD_DEVIATION 14.5
Cerebellar Brain Inhibition	0.94 milli volt STANDARD_DEVIATION 0.12
International Cooperative Ataxia Rating Scale (ICARS) score	53.0 units on a scale STANDARD_DEVIATION 18.6
Race (NIH/OMB) American Indian or Alaska Native	0 Participants
Race (NIH/OMB) Asian	0 Participants
Race (NIH/OMB) Black or African American	0 Participants
Race (NIH/OMB) More than one race	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants
Race (NIH/OMB) White	20 Participants
Region of Enrollment Italy	20 participants
Scale for the Assessment and Rating of Ataxia (SARA) score	20.2 units on a scale STANDARD_DEVIATION 7.4
Sex: Female, Male Female	10 Participants
Sex: Female, Male Male	10 Participants
Short-Form Health Survey 36	54.7 units on a scale STANDARD_DEVIATION 17.5

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	0 / 10	0 / 11
other Total, other adverse events	0 / 10	0 / 11
serious Total, serious adverse events	0 / 10	0 / 11

Outcome results

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).

Time frame: Baseline - 2 weeks

Arm	Measure	Group	Value (MEAN)	Dispersion
Real tDCS	Change in the International Cooperative Ataxia Rating Scale (ICARS) Score From Baseline	Baseline	53.0 units on a scale	Standard Deviation 18.6
Real tDCS	Change in the International Cooperative Ataxia Rating Scale (ICARS) Score From Baseline	2 Weeks	43.0 units on a scale	Standard Deviation 19.6
Sham tDCS	Change in the International Cooperative Ataxia Rating Scale (ICARS) Score From Baseline	Baseline	52.7 units on a scale	Standard Deviation 19.4
Sham tDCS	Change in the International Cooperative Ataxia Rating Scale (ICARS) Score From Baseline	2 Weeks	52.1 units on a scale	Standard Deviation 19.7

p-value: <0.001ANCOVA

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).

Time frame: Baseline - 2 weeks

Arm	Measure	Value (MEAN)	Dispersion
Real tDCS	Change in the Scale for the Assessment and Rating of Ataxia (SARA) Score From Baseline	15.8 units on a scale	Standard Deviation 7.6
Sham tDCS	Change in the Scale for the Assessment and Rating of Ataxia (SARA) Score From Baseline	19.7 units on a scale	Standard Deviation 7.5

p-value: <0.001ANCOVA

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.