RFC1 Natural History Study
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: Clinical rating scale to measure ataxia disease severity and progression.
- Who it may be relevant to
- Registry conditions: Ataxia. Basic parameters: from 18 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- Australia, Brazil, France, Germany, Italy +2
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
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Overview
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.
Interventions
- Other Clinical rating scale to measure ataxia disease severity and progression
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.
Primary outcome measures
- Change of Scale for the Assessment and Rating of Ataxia (SARA) from baseline to 2-year follow-up. [Time frame: 24 months]
Secondary outcome measures (3)
- 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]
Eligibility criteria
Inclusion criteria
- 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
Exclusion criteria
- RFC1: Missing informed consent
- Controls: evidence of neuropathy, neurodegenerative disease, or movement disorder; inability to give informed consent
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: Yes
Study design
- Observational model
- Cohort
Study locations
Germany · 3 centers
- Center for Neurology & Hertie-Institute for Clinical Brain Research, Dept. for Neurodegene — Tübingen
- German Center for Neurodegenerative Diseases (DZNE) — Bonn
- Department of Neurology University Hospital Schleswig Holstein — Lübeck
Italy · 2 centers
- Università degli Studi di Napoli 'Federico II', c/o AOU Federico II — Naples
- IRCCS Fondazione Stella Maris — Pisa
Australia · 1 center
- Department of Neuroscience, Central Clinical School, Monash University — Melbourne
Brazil · 1 center
- Department of Neurology, Ataxia Unit, Universidade Federal de São Paulo — São Paulo
France · 1 center
- Service de Neurologie, Hôpitaux Universitaires de Strasbourg — Strasbourg
New Zealand · 1 center
- Centre of Brain Research Neurogenetics Research Clinic, University of Auckland — Auckland
Turkey (Türkiye) · 1 center
- Koç University Hospital, KUTTAM-NDAL — Istanbul
Identifiers
NCT: NCT05177809 · RFC1-NHS