RFC1 Natural History Study
ConditionAtaxia
Trial statusRecruiting
Trial phaseNot listed
Trial typeObservational
Biological sexAll
Age18+
SponsorProf. Dr. Matthis Synofzik
About this trial
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.
Eligibility criteria
This trial accepts healthy volunteersQualifiers
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
Disqualifiers
RFC1: Missing informed consent
Controls: evidence of neuropathy, neurodegenerative disease, or movement disorder; inability to give informed consent
Trial 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.
Trial design
Design model
Cohort
Time perspective
Prospective
Treatments tested in this trial
Clinical rating scale to measure ataxia disease severity and progression
Other interventionSARA 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.
Treatment groups
150 Participants
are divided into 2 treatment groupsGroup A: RFC11 intervention
Group B: Unrelated healthy controls0 interventions
Trial outcomes
Primary outcomes
1
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.
Time frame
24 monthsSecondary outcomes
1
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.
Time frame
24 months2
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.
Time frame
24 months3
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).
Time frame
24 monthsOther outcomes
1
Composite Autonomic Symptom Score (COMPASS-31) at baseline, and eventually from baseline to 2-year follow-up if baseline data supports further use.
Severity of dysautonomia will be assessed by application of the Composite Autonomic Symptom Score (COMPASS-31). The total score is calculated as the weighted sum of 31 questions items, yielding a total autonomic symptom score between 0 and 100. Hereby, higher COMPASS-31 cores indicate more severe dysautonomia. This module is optional in the RFC1 cohort and unrelated healthy controls.
Time frame
24 months2
Cerebellar cognitive-affective syndrome scale (CCAS) from baseline to 2-year follow-up.
Severity of cognitive impairment will be assessed by application of the Cerebellar cognitive-affective syndrome scale (CCAS). The total score of 15 items comprises the number of failed items (with 3 or more failed items indicating definite cerebellar cognitive-affective syndrome), and a raw total score between 0 and 120. Hereby, lower CCAS raw cores indicate more severe cognitive impairment. This module is optional in the RFC1 cohort and unrelated healthy controls.
Time frame
24 months3
Clinical Assessment of Dysphagia in Neurodegeneration (CADN) from baseline to 2-year follow-up.
Severity of dysphagia will be assessed by application of the Clinical Assessment of Dysphagia in Neurodegeneration (CADN), comprising a history part and an examination with consumption. The total score is calculated as the weighted sum of 11 items, yielding a total score between 0 and 10. Hereby, higher CADN scores indicate more severe dysphagia. This module is optional in the RFC1 cohort.
Time frame
24 months4
Video Head Impulse Test (vHIT) from baseline to 2-year follow-up.
Vestibular function will be quantified by application of the Video Head Impulse Test (vHIT) of the horizontal semicircular canals, and eventually the vertical semicircular canals. This test yields the gain (ratio of eye velocity to head velocity) as a measure of vestibular function, yielding total scores between 0 and 1. Hereby, lower gains indicate more severe vestibular impairment. This module is optional in the RFC1 cohort and unrelated healthy controls.
Time frame
24 monthsSponsors and contacts
Click on the lead sponsor to view all of their trials.
Prof. Dr. Matthis Synofzik
Lead sponsor
University Hospital Tuebingen
Sponsor institution
Source ClinicalTrials.gov