RFC1 Natural History Study (RFC1-NHS)

Prof. Dr. Matthis Synofzik

Status: Enrolling

Conditions: Ataxia

Treatments: Other: Clinical rating scale to measure ataxia disease severity and progression

Study type: Observational

Funder types: Other

Identifiers

NCT05177809

RFC1-NHS

Details and patient eligibility

About

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.

Full 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.

Enrollment: 150 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

150 participants in 2 patient groups

RFC1

Description:

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.

Treatment:

Other: Clinical rating scale to measure ataxia disease severity and progression

Unrelated healthy controls

Description:

Unrelated healthy controls Healthy controls may undergo the same study procedures as the RFC1 cohort. Target sample size for the control cohort is 50.