RFC1 Natural History Study

NCT ID: NCT05177809

Last Updated: 2024-06-20

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Total Enrollment

150 participants

Study Classification

OBSERVATIONAL

Study Start Date

2021-12-14

Study Completion Date

2025-12-31

Brief Summary

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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

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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

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Ataxia

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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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.

Clinical rating scale to measure ataxia disease severity and progression

Intervention Type OTHER

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.

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.

No interventions assigned to this group

Interventions

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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.

Intervention Type OTHER

Other Intervention Names

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Scale for the Assessment and rating of Ataxia (SARA)

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Prof. Dr. Matthis Synofzik

OTHER

Sponsor Role lead

Responsible Party

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Prof. Dr. Matthis Synofzik

Principal Investigator, Leading Consultant

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Matthis Synofzik, Prof. Dr.

Role: PRINCIPAL_INVESTIGATOR

University Hospital Tübingen

Andreas Traschütz, Dr. Dr.

Role: PRINCIPAL_INVESTIGATOR

University Hospital Tübingen

Locations

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Department of Neuroscience, Central Clinical School, Monash University

Melbourne, Victoria, Australia

Site Status RECRUITING

Department of Neurology, Ataxia Unit, Universidade Federal de São Paulo

São Paulo, State of São Paulo, Brazil

Site Status RECRUITING

Service de Neurologie, Hôpitaux Universitaires de Strasbourg

Strasbourg, , France

Site Status RECRUITING

Center for Neurology & Hertie-Institute for Clinical Brain Research, Dept. for Neurodegenerative Diseases

Tübingen, Baden-Wurttemberg, Germany

Site Status RECRUITING

German Center for Neurodegenerative Diseases (DZNE)

Bonn, North Rhine-Westphalia, Germany

Site Status RECRUITING

Department of Neurology University Hospital Schleswig Holstein

Lübeck, Schleswig-Holstein, Germany

Site Status RECRUITING

Università degli Studi di Napoli 'Federico II', c/o AOU Federico II

Napoli, , Italy

Site Status RECRUITING

IRCCS Fondazione Stella Maris

Pisa, , Italy

Site Status RECRUITING

Centre of Brain Research Neurogenetics Research Clinic, University of Auckland

Auckland, , New Zealand

Site Status RECRUITING

Koç University Hospital, KUTTAM-NDAL

Istanbul, , Turkey (Türkiye)

Site Status RECRUITING

Countries

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Australia Brazil France Germany Italy New Zealand Turkey (Türkiye)

Central Contacts

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Matthis Synofzik, Prof. Dr.

Role: CONTACT

+49 7071 29 ext. 82060

Andreas Traschütz, Dr. Dr.

Role: CONTACT

+49 7071 29 ext. 82060

Facility Contacts

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Ian Harding, PhD

Role: primary

+61 3 9905 ext. 9283

Adam Vogel, PhD

Role: backup

, +61 3 9035 ext. 5334

José Luiz Pedroso, MD

Role: primary

+55 11 ext. 976449929

Paula Camila Alves, MD

Role: backup

+55 11 ext. 948223643

Thomas Wirth, Dr.

Role: primary

Lisa Graf, MSc

Role: primary

+49 7071 29 ext. 85374

Doreen Müller

Role: backup

+49 7071 29 ext. 85353

Jennifer Faber, Dr.

Role: primary

Madita Grümmer

Role: primary

+49 451 500 ext. 43440

Francesco Saccà, Prof.

Role: primary

Filippo M. Santorelli, MD

Role: primary

+39 050 ext. 886275

Ivana Ricca, MD

Role: backup

39 050 ext. 886311

Ashleigh O'Mara Baker

Role: primary

Nazli BAŞAK, PhD

Role: primary

+90-850 ext. 250825023811

Atay Vural, MD, PhD

Role: backup

+90-850 ext. 850 250 8250

Related Links

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http://arca-registry.org

Website of the ARCA Registry

Other Identifiers

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RFC1-NHS

Identifier Type: -

Identifier Source: org_study_id

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