The effects of transcranial cerebellar electrical stimulation on symptoms in Friedreich ataxia

ISRCTN	ISRCTN11920565
DOI	https://doi.org/10.1186/ISRCTN11920565
ClinicalTrials.gov (NCT)	Nil known
Clinical Trials Information System (CTIS)	Nil known
Protocol serial number	P2021/347
Sponsor	HUB-Hôpital Erasme, Université Libre de Bruxelles
Funders	Friedreich's Ataxia Research Alliance, Fonds De La Recherche Scientifique - FNRS, Fonds Erasme

Submission date: 10/01/2023
Registration date: 16/01/2023
Last edited: 30/05/2023

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Nervous System Diseases

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Background and study aims
The cerebellum modulates a wide range of motor and cognitive behaviours thanks to reciprocal connections between the cerebellum and the brain cortex. The main cerebellar output structure is the dentate nucleus (DN) that targets the brain cortex through the dentato-thalamo-cortical tract (DTC). Friedreich ataxia (FRDA) is the most common autosomal recessive ataxia and is hallmarked by DN progressive atrophy and associated DTC impairment. Patients display progressive cerebellar ataxia and a wide spectrum of cognitive impairments whose severity progresses in parallel to motor symptoms severity, suggesting a common core pathophysiology. Cerebellar transcranial direct current stimulation (ctDCS) is a non-invasive technique that may improve DTC functioning. ctDCS has shown efficacy in improving motor and cognitive performances in degenerative ataxia of mixed origins but its mechanisms are poorly characterized. This study aims to understand the relationship between the DTC, brain functional architecture and clinical phenotype in FRDA and assess the potential efficacy of ctDCS to alleviate FRDA symptoms.

Who can participate?
Patients with FRDA

What does the study involve?
Patients in the study will have anodal ctDCS or sham stimulation applied for 20 minutes a day for five consecutive days. At the beginning and end of the stimulation period, subjects will undergo clinical and brain functional imaging assessment with functional magnetic resonance imaging (fMRI).

What are the possible benefits and risks of participating?
Benefits to participating will be the potential clinical improvement in ataxic motor symptoms, finger tapping accuracy, cognitive performances as well as modulation of brain resting state functional connectivity. In the current state of knowledge, we believe that, if the subject has no contraindications to MRI, examinations performed by MRI do not involve any risk or danger for participants. Similarly, transcranial stimulation of the cerebellum is a process that has already been studied and the protocol for performing the stimulation is now well known. Rarely reported side effects do occur during stimulation and consist of a metallic taste and an itching or tingling sensation under the electrodes. To remedy these effects there are sugary drinks and menthol pastilles available. For tingling, cool compresses are available.

Where is the study run from?
HUB-Erasme Hospital, Free University of Brussels (HUB-Hôpital Erasme, Université Libre de Bruxelles) (Belgium)

When is the study starting and how long is it expected to run for?
June 2021 to November 2022

Who is funding the study?
1. Friedreich's Ataxia Research Alliance (USA)
2. Belgian National Fund for Scientific Research (Belgium)
3. Erasmus Fund for Medical Research (Belgium)

Who is the main contact?
Prof Gilles Naeije, gilles.naeije@erasme.ulb.ac.be (Belgium)

Contact information

Prof Gilles Naeije
Principal investigator

HUB-Hôpital Erasme
808, Route de Lennik
Brussels
1070
Belgium

Phone	+3225558196
Email	gilles.naeije@erasme.ulb.ac.be

Prof Gilles Naeije
Scientific

HUB-Hôpital Erasme, Neurology department
808, Route de Lennik
Anderlecht
1070
Belgium

Phone	+3225558196
Email	gilles.naeije@erasme.ulb.ac.be

Prof Gilles Naeije
Public

HUB-Hôpital Erasme, Neurology department
808, Route de Lennik
Anderlecht
1070
Belgium

Phone	+3225558196
Email	gilles.naeije@erasme.ulb.ac.be

Study information

Primary study design	Interventional
Study design	Prospective interventional randomized sham-controlled trial
Secondary study design	Randomised cross over trial
Participant information sheet	43019_PIS_Patients_2022.pdf
Scientific title	Dentato-thalamo-cortical tracts in Friedreich ataxia: impact of its modulation on Friedreich ataxia symptoms and brain functional architecture
Study acronym	FRDA_ctDCS
Study objectives	Anodal cerebellar transcranial direct current stimulation (ctDCS) will improve motor and cognitive symptoms in Friedreich ataxia by restoring cerebellar cortical inhibition
Ethics approval(s)	Approved 23/08/2021, Ethics Committee Hôpital Erasme (Ethics Committee Erasme HUB-Hôpital Erasme, 808, route de Lennik, 1070 Anderlecht, Belgium; +32 (0)2 555 37 07; comite.ethique@erasme.ulb.ac.be), ref: B4062021000183
Health condition(s) or problem(s) studied	Friedreich ataxia
Intervention	The function Randperm (2) in the Matlab program will be used to allocate the subjects either to the intervention first and the sham intervention second or the other way around. Participating Friedreich's ataxia patients will be included in a randomized cross-over sham-controlled study where anodal cerebellar transcranial direct current stimulation (ctDCS)/sham stimulation will be applied for 20 minutes a day for five consecutive days. At the beginning and end of the stimulation period, subjects will undergo clinical and brain functional imaging assessment with functional magnetic resonance imaging (fMRI).
Intervention type	Device
Phase	Not Applicable
Drug / device / biological / vaccine name(s)	ctDCS
Primary outcome measure(s)	1. Impairments in cerebellar ataxia measured using the Scale for the Assessment and Rating of Ataxia (SARA) before and after intervention 2. Assessment of cerebellar ataxia measured using the Composite Cerebellar Functional Severity Score (CCFS) before and after intervention 3. Cerebellar cognitive affective syndrome measured using the Cerebellar Cognitive Affective Score (CCAS) before and after intervention
Key secondary outcome measure(s)	Somatosensory cortices evoked response to a tactile oddball paradigm measured using functional magnetic resonance imaging (fMRI) before and after intervention
Completion date	01/11/2022

Eligibility

Participant type(s)	Patient
Age group	Mixed
Sex	All
Target sample size at registration	25
Total final enrolment	24
Key inclusion criteria	Clinically confirmed Friedreich ataxia
Key exclusion criteria	Other comorbid neurological diseases
Date of first enrolment	01/09/2021
Date of final enrolment	01/06/2022

Locations

Countries of recruitment

Belgium

Study participating centre

HUB-Hôpital Erasme, Université Libre de Bruxelles

808, route de Lennik
Anderlecht
1070
Belgium

Results and Publications

Individual participant data (IPD) Intention to share	Yes
IPD sharing plan summary	Available on request
IPD sharing plan	Datasets generated during and /or analysed during the current study will be available upon request from gilles.naeije@erasme.ulb.ac.be. The data shared upon request will be patients' characteristics, behavioural scores (SARA, CCAS, CCFS) and fMRI raw files, at group and subject levels.

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Basic results			30/05/2023	No	No
Participant information sheet	English		16/01/2023	No	Yes
Participant information sheet	French, parent and patients aged 14-17 version 2.0	17/08/2021	16/01/2023	No	Yes
Participant information sheet	French, patients version 2.0	17/08/2021	16/01/2023	No	Yes
Participant information sheet	French, patients aged 14-17 version 1.0	17/02/2015	16/01/2023	No	Yes
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes

Additional files

43019_PIS_Parent_Patients14-17yr_v2.0_17Aug2021.pdf: French, parent and patients aged 14-17
43019_PIS_Patients_v2.0_17Aug2021.pdf: French, patients
43019_PIS_Patients14-17yrs_v1.0_17Feb2015.pdf: French, patients aged 14-17
43019_PIS_Patients_2022.pdf: English
ISRCTN11920565_BasicResults.pdf: Basic results

Editorial Notes

30/05/2023: The basic results summary has been uploaded.
16/01/2023: Trial's existence confirmed by Ethics Committee Hôpital Erasme.