Spinocerebellar Ataxia Type 27B Natural History Study (SCA27B-NHS)

This international, multi-center, multi-modal, and prospective observational cohort study aims to validate trial outcomes for capturing disease progression in Spinocerebellar Ataxia Type 27B (SCA27B), with combined multi-modal capture of clinical outcome assessments, digital-motor assessments, and molecular biomarkers.

Study Overview

• Status: Recruiting
• Conditions: Spinocerebellar Ataxia Type 27B

Detailed Description

The investigators will perform an international, multi-center, multi-modal, and registry-based standardized prospective Natural History Study (NHS) in Spinocerebellar Ataxia Type 27B (SCA27B), including the presymptomatic phase of the disease (i.e. presymptomatic subjects at risk for SCA27B). Participants will be assessed annually. Clinical data, including clinician-reported outcomes and patient-focused outcomes, will be entered into a clinical database customized to the requirements of this specific study (SCA27B Registry; www.ataxia-registries.org). Digital-motor outcomes comprise digital gait assessment by wearable sensors, and digital assessment of upper limb movements by Q-Motor. At all study visits, participants will be asked to donate biosamples; and participants can elect to participate in sampling of blood, urine, CSF, and/or a skin biopsy. Based on this multimodal protocol, the study aims to determine the most sensitive, comprehensive, and reliable outcome measures for future therapeutic trials in SCA27B.

• Study Type: Observational
• Enrollment (Estimated): 300

Contacts and Locations

• Study Contact: Name: Matthis Synofzik, Prof. Dr.; Phone Number: 82060 +49 7071 29; Email: matthis.synofzik@uni-tuebingen.de
• Study Contact Backup: Name: Andreas Traschütz, Dr. Dr.; Phone Number: 61890 +49 7071 29; Email: andreas.traschuetz@uni-tuebingen.de

Study Locations

• Czechia
  • Prague, Czechia, 15006
    • Recruiting
    • Department of Neurology, Motol University Hospital, Second Faculty of Medicine, Charles University
    • Contact: Olga Brýksiová; Phone Number: +420 702 269 277; Email: ataxie@fnmotol.cz
    • Principal Investigator: Martin Vyhnálek, Assoc. Prof., MD., Ph.D.
    • Sub-Investigator: Zuzana Blichová, MD
• Germany
  • Baden-Wurttemberg
    • Tübingen, Baden-Wurttemberg, Germany, 72076
      • Recruiting
      • Center for Neurology & Hertie-Institute for Clinical Brain Research, Dept. for Neurodegenerative Diseases
      • Contact: Lisa Graf, MSc; Phone Number: 85374 +49 7071 29; Email: lisa.graf@med.uni-tuebingen.de
      • Principal Investigator: Matthis Synofzik, Prof. Dr.
      • Principal Investigator: Andreas Traschütz, Dr. Dr.
  • North Rhine-Westphalia
    • Essen, North Rhine-Westphalia, Germany, 45147
      • Recruiting
      • Department of Neurology & Center for Translational Neuro- and Behavioral Sciences, Essen University Hospital, University of Duisburg-Essen
      • Contact: Friedrich Erdlenbruch, Dr.; Phone Number: 2180 +49 201 723; Email: friedrich.erdlenbruch@uk-essen.de
      • Principal Investigator: Dagmar Timmann, Prof. Dr.
• Italy
  • Pisa, Italy, 56128
    • Recruiting
    • IRCCS Fondazione Stella Maris
    • Contact: Filippo M. Santorelli, MD; Phone Number: +39 050 886275; Email: filippo.santorelli@fsm.unipi.it
    • Principal Investigator: Filippo M. Santorelli, MD
    • Contact: Sara Satolli, MD; Email: sara.satolli@gmail.com
    • Sub-Investigator: Sara Satolli, MD
• Spain
  • Gipuzkoa
    • San Sebastián, Gipuzkoa, Spain, 20014
      • Recruiting
      • Department of Neurology, Donostia University Hospital, BioGipuzkoa Health Research Institute
      • Contact: Ioana Croitoru, SC; Phone Number: 7027 +34 94300; Email: ioana.croitoru@bio-gipuzkoa.eus
      • Principal Investigator: Javier Ruiz Martinez, Prof. Dr.
      • Sub-Investigator: Ana Vinagre Aragon, Dr.
      • Sub-Investigator: Elisabet Mondragon Rezola, Dr.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

This study enrolls participants with clinically manifest and genetically confirmed SCA27B and first-disease relatives at-risk for SCA27B, as well as healthy unrelated controls to contrast unspecific, age- or sex-related findings to disease-related specific findings.

Description

Inclusion Criteria:

• SCA27B: genetic diagnosis of ≥250 uninterrupted GAA repeat expansions in FGF14
• SCA27B risk subject: asymptomatic first-degree relative of SCA27B participant with known or unknown carrier status
• 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:

• SCA27B: Missing informed consent
• SCA27B risk subjects: Missing informed consent
• Unrelated healthy controls: Missing informed consent, or concurrent neurological, orthopedic, or other diseases interfering with the motor assessments

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort
SCA27B; Participants with genetically confirmed SCA27B (OMIM 620174), i.e. ≥250 uninterrupted GAA repeat expansions in FGF14, will be recruited. Target sample size for the SCA27B cohort is 200 participants.
SCA27B risk subjects; First-degree relatives at risk for SCA27B, both with known and unknown carrier status, will be included to capture presymptomatic disease stages. Target sample size for the risk cohort is 50 participants
Unrelated healthy controls; Unrelated healthy controls may undergo the same study procedures as the SCA27B cohort to determine age-related effects on the multimodal outcomes. Target sample size for the control cohort is 50.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Friedreich Ataxia Rating Scale - Neurological Examination Part E (upright stability) from baseline to 2-year follow-up	Severity of ataxia in the gait and balance domain will be assessed by application of part E of the neurological examination of Friedreich Ataxia Rating Scale (FARS-E). The total score is calculated as the sum of 7 items, yielding a total score between 0 and 28. Hereby, higher FARS-E scores indicate more severe functional impairment.	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of Scale for the Assessment and Rating of Ataxia (SARA) from baseline to 2-year follow-up	Severity of ataxia 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.	24 months
Friedreich Ataxia Rating Scale - Activities of Daily Living (FARS-ADL) from baseline to 2-year follow-up	Impairment in activities of daily living will be assessed 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.	24 months
Patient Global Impression of Change (PGI-C) from baseline to 1-year and 2-year follow-up	Patient-experienced longitudinal change of ataxia severity will be assessed by asking for the Patient Global Impression of Change (PGI-C) as patient-reported outcome and anchor for longitudinal validation of other outcomes. The PGI-C consists of 7 levels from 1 = very much worse, to 4 = no change, to 7 = very much improved.	24 months
Digital gait and balance assessment from baseline to 2-year follow-up	Gait and balance will be assessed digitally with body-worn sensors (inertial measurement units), which record acceleration or rotational movements during specific gait and balance tasks.	24 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Friedreich Ataxia Rating Scale - Functional Staging from baseline to 2-year follow-up	Global severity will be assessed by application of the functional staging of the Friedreich Ataxia Rating Scale. The functional staging ranges from 1 (minimal signs detected by physician) to 6 (confined to wheelchair and total dependency). Hereby, higher functional stages indicate more severe functional impairment.	24 months
Activities-specific Balance Confidence Scale (ABC Scale) from baseline to 2-year follow-up	Balance problems experienced by the participant will be assessed by application of the Activities-specific Balance Confidence Scale (ABC Scale) as patient-reported outcome. The total score is calculated as the average of 16 items, yielding a total score between 0 and 100% confidence in balance. Hereby, lower scores on the ABC Scales indicate more severe disease.	24 months
Digital assessment of upper limb movement from baseline to 2-year follow-up	Motor impairment of the upper and lower limb will be assessed digitally with a quantitative motor examination (Q-Motor) of finger tapping, diadochokinesia and visually guided target reaching.	24 months

Collaborators and Investigators

• Sponsor: University Hospital Tuebingen
• Investigators: Principal Investigator: Matthis Synofzik, Prof. Dr., University Hospital Tübingen; Principal Investigator: Andreas Traschütz, Dr. Dr., University Hospital Tübingen

Study record dates

Study Major Dates

• Study Start (Actual): June 4, 2024
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 31, 2028

Study Registration Dates

• First Submitted: June 18, 2024
• First Submitted That Met QC Criteria: June 18, 2024
• First Posted (Actual): June 25, 2024

Study Record Updates

• Last Update Posted (Actual): April 6, 2026
• Last Update Submitted That Met QC Criteria: March 30, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Natural History Study; ataxia; SCA27B; FGF14; Outcome Validation
• Additional Relevant MeSH Terms: Neurologic Manifestations; Nervous System Diseases; Dyskinesias; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Ataxia
• Other Study ID Numbers: SCA27B-NHS

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: Individual participant data will be shared upon reasonable request.

Drug and device information, study documents

• product manufactured in and exported from the U.S.: No