The effects of transcranial cerebellar electrical stimulation on symptoms in Friedreich ataxia
| ISRCTN | ISRCTN11920565 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN11920565 |
| Secondary identifying numbers | P2021/347 |
- 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
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
Principal Investigator
HUB-Hôpital Erasme
808, Route de Lennik
Brussels
1070
Belgium
| Phone | +3225558196 |
|---|---|
| gilles.naeije@erasme.ulb.ac.be |
Scientific
HUB-Hôpital Erasme, Neurology department
808, Route de Lennik
Anderlecht
1070
Belgium
| Phone | +3225558196 |
|---|---|
| gilles.naeije@erasme.ulb.ac.be |
Public
HUB-Hôpital Erasme, Neurology department
808, Route de Lennik
Anderlecht
1070
Belgium
| Phone | +3225558196 |
|---|---|
| gilles.naeije@erasme.ulb.ac.be |
Study information
| Study design | Prospective interventional randomized sham-controlled trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised cross over trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| 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 |
| Pharmaceutical study type(s) | |
| Phase | Not Applicable |
| Drug / device / biological / vaccine name(s) | ctDCS |
| Primary outcome measure | 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 |
| Secondary outcome measures | Somatosensory cortices evoked response to a tactile oddball paradigm measured using functional magnetic resonance imaging (fMRI) before and after intervention |
| Overall study start date | 01/06/2021 |
| Completion date | 01/11/2022 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Mixed |
| Sex | Both |
| Target number of participants | 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
Anderlecht
1070
Belgium
Sponsor information
Hospital/treatment centre
HUB-Hôpital Erasme
808, Route de Lennik
Anderlecht
1070
Belgium
| Phone | +3225553111 |
|---|---|
| FlexStaff.SRB.erasme@hubruxelles.be | |
| Website | http://www.ulb.ac.be/ |
Funders
Funder type
Research organisation
Government organisation / Trusts, charities, foundations (both public and private)
- Alternative name(s)
- FA Research Alliance, FARA
- Location
- United States of America
Government organisation / Local government
- Alternative name(s)
- F.R.S. - FNRS, Fund for Scientific Research - FNRS, Belgian National Fund for Scientific Research, FNRS
- Location
- Belgium
Government organisation / Trusts, charities, foundations (both public and private)
- Alternative name(s)
- Erasmus Fund, Erasmus Fund for Medical Research, Fonds Erasme pour la Recherche Médicale
- Location
- Belgium
Results and Publications
| Intention to publish date | 01/02/2023 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| Publication and dissemination plan | Planned publication in a high-impact peer-reviewed journal |
| 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? |
|---|---|---|---|---|---|
| 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 |
| Basic results | 30/05/2023 | No | No |
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
Editorial Notes
30/05/2023: The basic results summary has been uploaded.
16/01/2023: Trial's existence confirmed by Ethics Committee Hôpital Erasme.
