AtaxiaRFC1-NHSNCT05177809
RFC1 Natural History Study
An observational study of Ataxia, run by Prof. Dr. Matthis Synofzik at 10 sites in 7 countries.
Trial summary
This international, multi-center, multi-modal and prospective observational study aims to determine the phenotypic spectrum and the natural progression of the RFC1 repeat expansion disease, and to seek and validate digital, imaging, and molecular biomarkers that aid in diagnosis and serve as outcome measures in future… Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Ataxia
- What is being tested?
- Clinical rating scale to measure ataxia disease severity and progression
- How many people
- 150 participants
- Where
- 10 sitesin 7 countries
- Study dates
- 14 Dec 2021to Dec 2026
- How long will I take part?
- 24 Months
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: This study enrolls probands with clinically manifest and genetically confirmed RFC1 repeat expansion disease, as well as healthy unrelated controls to contrast unspecific, age- or sex-related findings to disease-related specific findings.
Who may be able to join
- RFC1: genetic diagnosis of bi-allelic pathogenic repeat expansions in RFC1
- Unrelated healthy controls: no signs or history of neurological or psychiatric disease AND
- Written informed consent AND
- Participants are willing and able to comply with study procedures
Who cannot join
- RFC1: Missing informed consent
- Controls: evidence of neuropathy, neurodegenerative disease, or movement disorder; inability to give informed consent
Trial locations and contacts
10 sites in 7 countries. Contact the study team or a site near you to ask about taking part.
10 sites in 7 countries
Germany3 sites, 3 recruiting
- Recruiting
German Center for Neurodegenerative Diseases (DZNE)
Bonn, North Rhine-Westphalia, 53127
Jennifer Faber, Dr., jennifer.faber@ukbonn.de
Jennifer Faber, Dr.
- Recruiting
Department of Neurology University Hospital Schleswig Holstein
Lübeck, Schleswig-Holstein, 23562
Madita Grümmer, +49 451 500 ext. 43440, madita.gruemmer@neuro.uni-luebeck.de
Norbert Brüggemann, Prof. Dr.
- Recruiting
Center for Neurology & Hertie-Institute for Clinical Brain Research, Dept. for Neurodegenerative Diseases
Tübingen, Baden-Wurttemberg, 72076
Lisa Graf, MSc, +49 7071 29 ext. 85374, lisa.graf@med.uni-tuebingen.de
Doreen Müller, +49 7071 29 ext. 85353, doreen.mueller@med-uni-tuebingen.de
Italy2 sites, 2 recruiting
- Recruiting
Università degli Studi di Napoli 'Federico II', c/o AOU Federico II
Naples, Napoli, 80131
Francesco Saccà, Prof., francesco.sacca@unina.it
Francesco Saccà, Prof.
- Recruiting
IRCCS Fondazione Stella Maris
Pisa, 56128
Filippo M. Santorelli, MD, +39 050 ext. 886275, filippo.santorelli@fsm.unipi.it
Ivana Ricca, MD, 39 050 ext. 886311, ivanaricca.fsm@gmail.com
Australia1 site, 1 recruiting
- Recruiting
Department of Neuroscience, Central Clinical School, Monash University
Melbourne, Victoria, 3004
Ian Harding, PhD, +61 3 9905 ext. 9283, Ian.Harding@monash.edu
Adam Vogel, PhD, , +61 3 9035 ext. 5334, vogela@unimelb.edu.au
Brazil1 site, 1 recruiting
- Recruiting
Department of Neurology, Ataxia Unit, Universidade Federal de São Paulo
São Paulo, State of São Paulo, 04040-003
José Luiz Pedroso, MD, +55 11 ext. 976449929, zeluizpedroso@yahoo.com.br
Paula Camila Alves, MD, +55 11 ext. 948223643, paulacamila_alves@hotmail.com
France1 site, 1 recruiting
- Recruiting
Service de Neurologie, Hôpitaux Universitaires de Strasbourg
Strasbourg, Strasbourg, 67000
Thomas Wirth, Dr., thomas.wirth@chru-strasbourg.fr
Mathieu Anheim, Prof.
New Zealand1 site, 1 recruiting
- Recruiting
Centre of Brain Research Neurogenetics Research Clinic, University of Auckland
Auckland, 1142
Ashleigh O'Mara Baker, cbr.nrc@auckland.ac.nz
Richard Roxburgh, Prof.
Turkey (Türkiye)1 site, 1 recruiting
- Recruiting
Koç University Hospital, KUTTAM-NDAL
Istanbul, 34010
Nazli BAŞAK, PhD, +90-850 ext. 250825023811, nbasak@ku.edu.tr
Atay Vural, MD, PhD, +90-850 ext. 850 250 8250, atayvural@ku.edu.tr
About this study
This international, multi-center, multi-modal and prospective observational study aims to determine the phenotypic spectrum and the natural progression of the RFC1 repeat expansion disease, and to seek and validate digital, imaging, and molecular biomarkers that aid in diagnosis and serve as outcome measures in future clinical trials of this novel, but frequent ataxia with late adult-onset.
Read the detailed description
The investigators will perform an international, multi-center, multi-modal, and registry-based standardized prospective Natural History Study (NHS) in RFC1 repeat expansion disease. Participants will be assessed annually. Study visits with a standardized clinical examination will apply several clinical rating scales, and data will be entered into a clinical database (ARCA Registry; www.ARCA-registry.org) customized to the requirements of this specific study. At all study visits, patients will be asked to donate biosamples; biomaterial collection is optional, and participants can elect to participate in sampling of blood, urine, CSF, and/or a skin biopsy.
Optionally, and depending on local availability at each participating site, additional examinations may be performed including imaging, quantitative movement and speech analysis, vestibular testing, a neuropsychological examination, or examination of swallowing function, all to fully capture the multisystemic presentation of the RFC1 repeat expansion disease.
This study will delineate variable phenotypes of this relatively novel disease, and systematically characterize the longitudinal progression of multi-model biomarkers to determine the most sensitive, comprehensive, and reliable outcomes measures for future therapeutic trials. Here, longitudinal validation of targeted fluid biomarker candidates will be an important part. The multi-modal longitudinal design of the study and its comprehensive assessment will also provide mechanistic insights into the multisystemic evolution of the disease, which will especially allow to track and understand selective as well as overlapping dysfunction of the cerebellum, sensory peripheral nerves, the vestibular system, and additional systems known to be involved in RFC1 disease or 'CANVAS' as its related syndrome.
- Conditions
- Ataxia
- Being tested
- Clinical rating scale to measure ataxia disease severity and progression
- Keywords
- RFC1, CANVAS, Natural History Study, Biomarker
- Medical subject headings
- Ataxia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Clinical rating scale to measure ataxia disease severity and progressionOther
Also called Scale for the Assessment and rating of Ataxia (SARA)
SARA is a clinical scale developed by Schmitz-Hübsch et al which assesses a range of different impairments in cerebellar ataxia. The scale is made up of 8 items related to gait, stance, sitting, speech, finger-chase test, nose-finger test, fast alternating movements and heel-shin test.
| Study group | Role | What they receive |
|---|---|---|
| RFC1 | Participants with genetically confirmed RFC1 repeat expansion disease (ORPHA: 504476; OMIM 102579) will be recruited. Target sample size for the RFC1 cohort is 100 participants. Receives: Other: Clinical rating scale to measure ataxia disease severity and progression | |
| Unrelated healthy controls | Unrelated healthy controls Healthy controls may undergo the same study procedures as the RFC1 cohort. Target sample size for the control cohort is 50. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change of Scale for the Assessment and Rating of Ataxia (SARA) from baseline to 2-year follow-up.
Severity of ataxia in the RFC1 cohort will be assessed by application of the Scale for the Assessment and Rating of Ataxia (SARA). The total score is calculated as the sum of 8 items, yielding a total score between 0 and 40. Hereby, higher SARA scores indicate more severe disease.
Measured: 24 months
Secondary outcomes (3)
Friedreich Ataxia Rating Scale - Activities of Daily Living (FARS-ADL) from baseline to 2-year follow-up.
Impairment in activities of daily living by ataxia, neuropathy, vestibular impairment or other disease features will be assessed in the RFC1 cohort by application of the Activities of Daily Living part of the Friedreich Ataxia Rating Scale (FARS-ADL). The total score is calculated as the sum of 9 items, yielding a total score between 0 and 36. Hereby, higher FARS-ADL scores indicate more severe functional impairment.
Measured: 24 months
Charcot-Marie-Tooth Examination Score Version 2 (CMTESv2) from baseline to 2-year follow-up.
Severity of neuropathy in the RFC1 cohort will be assessed by application of the Charcot-Marie-Tooth Examination Score Version 2 (CMTESv2). The total score is calculated as the sum of 7 items, yielding a total score between 0 and 28. Hereby, higher CMTESv2 scores indicate more severe neuropathy.
Measured: 24 months
Nine-Hole Peg Test (9HPT) from baseline to 2-year follow-up.
Upper limb function in the RFC1 cohort will be quantified by application of the Nine-Hole Peg Test (9HPT). This performance measure yields the mean duration of 2 trials to complete the task with the dominant and non-dominant hand, respectively, with an upper limit of 5 minutes (300 seconds).
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Jan 2022
- Study start14 Dec 2021
- Primary completionDec 2026 (estimated)
- Study completionDec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for AtaxiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 150 participants (estimated)
- Target duration
- 24 Months
Sponsor and investigators
- Lead sponsor
- Prof. Dr. Matthis Synofzik
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Prof. Dr. Matthis Synofzik, University Hospital Tuebingen
- Investigators
- Matthis Synofzik, Prof. Dr., Principal investigator, University Hospital TuebingenAndreas Traschütz, Dr. Dr., Principal investigator, University Hospital Tuebingen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05177809
- Sponsor's protocol ID
- RFC1-NHS
- Acronym
- RFC1-NHS
- Status last verified
- Mar 2026
- First submitted
- 14 Dec 2021
- Last updated
- 31 Mar 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 31 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- RFC1 Natural History Study
- ClinicalTrials.gov ID
- NCT05177809
- Acronym / sponsor ID
- RFC1-NHS / RFC1-NHS
- Conditions
- Ataxia
- Keywords
- RFC1, CANVAS, Natural History Study, Biomarker
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 150 participants (estimated)
- Lead sponsor
- Prof. Dr. Matthis SynofzikUniversity, hospital or other
- Study start
- 14 Dec 2021 (actual)
- Primary completion
- Dec 2026 (estimated)
- Study completion
- Dec 2026 (estimated)
- First posted
- 5 Jan 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This international, multi-center, multi-modal and prospective observational study aims to determine the phenotypic spectrum and the natural progression of the RFC1 repeat expansion disease, and to seek and validate digital, imaging, and molecular biomarkers that aid in diagnosis and serve as outcome measures in future clinical trials of this novel, but frequent ataxia with late adult-onset.
Detailed description
The investigators will perform an international, multi-center, multi-modal, and registry-based standardized prospective Natural History Study (NHS) in RFC1 repeat expansion disease. Participants will be assessed annually. Study visits with a standardized clinical examination will apply several clinical rating scales, and data will be entered into a clinical database (ARCA Registry; www.ARCA-registry.org) customized to the requirements of this specific study. At all study visits, patients will be asked to donate biosamples; biomaterial collection is optional, and participants can elect to participate in sampling of blood, urine, CSF, and/or a skin biopsy.
Optionally, and depending on local availability at each participating site, additional examinations may be performed including imaging, quantitative movement and speech analysis, vestibular testing, a neuropsychological examination, or examination of swallowing function, all to fully capture the multisystemic presentation of the RFC1 repeat expansion disease.
This study will delineate variable phenotypes of this relatively novel disease, and systematically characterize the longitudinal progression of multi-model biomarkers to determine the most sensitive, comprehensive, and reliable outcomes measures for future therapeutic trials. Here, longitudinal validation of targeted fluid biomarker candidates will be an important part. The multi-modal longitudinal design of the study and its comprehensive assessment will also provide mechanistic insights into the multisystemic evolution of the disease, which will especially allow to track and understand selective as well as overlapping dysfunction of the cerebellum, sensory peripheral nerves, the vestibular system, and additional systems known to be involved in RFC1 disease or 'CANVAS' as its related syndrome.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Target follow-up
- 24 Months
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| RFC1 | – | Other: Clinical rating scale to measure ataxia disease severity and progressionParticipants with genetically confirmed RFC1 repeat expansion disease (ORPHA: 504476; OMIM 102579) will be recruited. Target sample size for the RFC1 cohort is 100 participants. |
| Unrelated healthy controls | – | –Unrelated healthy controls Healthy controls may undergo the same study procedures as the RFC1 cohort. Target sample size for the control cohort is 50. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- This study enrolls probands with clinically manifest and genetically confirmed RFC1 repeat expansion disease, as well as healthy unrelated controls to contrast unspecific, age- or sex-related findings to disease-related specific findings.
Key inclusion criteria (4 listed)
- RFC1: genetic diagnosis of bi-allelic pathogenic repeat expansions in RFC1
- Unrelated healthy controls: no signs or history of neurological or psychiatric disease AND
- Written informed consent AND
- Participants are willing and able to comply with study procedures
Key exclusion criteria (2 listed)
- RFC1: Missing informed consent
- Controls: evidence of neuropathy, neurodegenerative disease, or movement disorder; inability to give informed consent
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Clinical rating scale to measure ataxia disease severity and progressionAlso: Scale for the Assessment and rating of Ataxia (SARA)SARA is a clinical scale developed by Schmitz-Hübsch et al which assesses a range of different impairments in cerebellar ataxia. The scale is made up of 8 items related to gait, stance, sitting, speech, finger-chase test, nose-finger test, fast alternating movements and heel-shin test. | Other | RFC1 |
Primary outcome
Change of Scale for the Assessment and Rating of Ataxia (SARA) from baseline to 2-year follow-up.
Time frame: 24 months
Severity of ataxia in the RFC1 cohort will be assessed by application of the Scale for the Assessment and Rating of Ataxia (SARA). The total score is calculated as the sum of 8 items, yielding a total score between 0 and 40. Hereby, higher SARA scores indicate more severe disease.
3 secondary outcomes
Friedreich Ataxia Rating Scale - Activities of Daily Living (FARS-ADL) from baseline to 2-year follow-up.
Time frame: 24 months
Charcot-Marie-Tooth Examination Score Version 2 (CMTESv2) from baseline to 2-year follow-up.
Time frame: 24 months
Nine-Hole Peg Test (9HPT) from baseline to 2-year follow-up.
Time frame: 24 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Mar 2026.
- Website of the ARCA RegistryLink provided by the sponsor.
- Individual participant dataSharing planned: Undecided
Related trials for Ataxia
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Cerebellar DBS in SCA1 and SCA3 Study
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Natural History of Spinocerebellar Ataxia Type 7 (SCA7)
Spinocerebellar Ataxia
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Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
Rare Disorders, Undiagnosed Disorders
RecruitingPhase 2
An Open-Label Study of CTI-1601 in Subjects With Friedreich's Ataxia
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RecruitingObservational study
Phenotype/Genotype Correlations in Movement Disorders
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Matthis Synofzik, Prof. Dr. principal investigator
University Hospital Tuebingen
Andreas Traschütz, Dr. Dr. principal investigator
University Hospital Tuebingen
10 sites in 7 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Ataxia, run by Prof. Dr. Matthis Synofzik at 10 sites in 7 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 31 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in Germany, Italy, Australia, Brazil, France and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Matthis Synofzik, Prof. Dr. (+49 7071 29 ext. 82060, matthis.synofzik@uni-tuebingen.de), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change of Scale for the Assessment and Rating of Ataxia (SARA) from baseline to 2-year follow-up. (time frame: 24 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Mar 2026.