Validation of the RADIAL Algorithm for Diagnosis of Autosomal Recessive Cerebellar Ataxia

NCT04261127 | Recruiting

• 1 other identifier: 7346
• Study Type: interventional
• Target: 400
• Locations: 1 country
• Sites: 8

Brief Summary

RADIAL is an algorithm which has been developed following a review of the literature on 67 autosomal recessive cerebellar ataxias (ARCA) and personal clinical experience. Frequency and specificity of each feature were defined for each autosomal recessive cerebellar ataxia, and corresponding prediction scores were assigned. Clinical and paraclinical features of patients are entered into the algorithm, and a patient's total score for each ARCA is calculated, producing a ranking of possible diagnoses. Sensitivity and specificity of the algorithm were assessed by blinded analysis of a multinational cohort of 834 patients with molecularly confirmed autosomal recessive cerebellar ataxia. The performance of the algorithm was assessed versus a blinded panel of autosomal recessive cerebellar ataxia experts. The correct diagnosis was ranked within the top 3 highest-scoring diagnoses at a sensitivity and specificity of \>90% for 84% and 91% of the evaluated genes, respectively. Mean sensitivity and specificity of the top 3 highest-scoring diagnoses were 92% and 95%, respectively. Our aim is now to validate in a prospective cohort of ARCA, the performance of RADIAL to predict the correct genetic diagnosis.

Conditions

Autosomal Recessive Cerebellar Ataxia

Keywords

autosomal recessive cerebellar ataxia; algorithm; genetic diagnosis

Outcome Measures

Primary Outcomes (1)

• Percentage of patients for whom the final genetic diagnosis is in the top 3 of the diagnoses proposed by the RADIAL algorithm (corresponding to the diseases with the 3 highest score given by the algorithm).

  The final diagnosis will be established after a genetic analysis and a medical interpretation of the results by geneticists.

  At final visit (depending of genetic results from 2 to 24 month maximum after inclusion visit)

Secondary Outcomes (5)

• Percentage of patients for whom the final genetic diagnosis is the first diagnosis proposed by the RADIAL algorithm (corresponding to the disease with the highest score given by the algorithm).

  At final visit (depending of genetic results from 2 to 24 month maximum after inclusion visit)

• Comparison of interpretation times by the clinical-genetic team (genetic and clinical data) with and without the help of the RADIAL algorithm

  At final visit (depending of genetic results from 2 to 24 month maximum after inclusion visit)

• Comparison of the satisfaction score given by the clinical-genetic team in the interpretation of data with and without the help of the RADIAL algorithm

  At final visit (depending of genetic results from 2 to 24 month maximum after inclusion visit)

• Influence of RADIAL on genetic diagnosis: percentage of patients whose diagnosis has been reviewed after the clinical-genetic team has learned of the results proposed by RADIAL

  At final visit (depending of genetic results from 2 to 24 month maximum after inclusion visit)

• Percentage of patients for whom the genome analysis will have detected a new gene.

  At final visit (depending of genetic results from 2 to 24 month maximum after inclusion visit)

Study Arms (1)

experimental arm

EXPERIMENTAL

The analysis of phenotypic data in RADIAL and the analysis of DNA (analysis of the Friedreich gene ± PMDA panel) will be performed for all patients in order to meet the main objective and the secondary objectives. Specifically for the secondary objectives (N ° 3, 4 and 5), randomization via eCRF (electronic case report form) will be performed for the interpretation of genetic analyzes (PMDA panel) without inducing any change for the patients. This randomization, by block and by center, will allow the attribution of one of the following two groups: * Control group: interpretation of genetic analyzes without the use of RADIAL; * Experimental group: interpretation of genetic analyzes using RADIAL. Genome analysis (secondary objective n ° 6) will be carried out for all the patients who remained without diagnosis at the end of the first part, and for whom the DNA of relatives is available.

Genetic: Genetic diagnosis (PMDA panel); Diagnostic Test: Use of RADIAL algorithm

Interventions

Genetic diagnosis (PMDA panel) GENETIC

Blood samples for DNA study

experimental arm

Use of RADIAL algorithm DIAGNOSTIC_TEST

RADIAL card filling (contains clinical and biological data)

experimental arm

Eligibility Criteria

• Age: 5 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• \- For patients:
• Patient, male or female, over 5 years old (no upper age limit)
• Patient with cerebellar ataxia who started before the age of 40
• Patient with a family history compatible with autosomal recessive inheritance (sporadic case, consanguinity, several cases in siblings)
• Patient in which an acquired cause of cerebellar ataxia has been excluded
• For patients over 18 years old: patient speaking and reading French, able to give a signed and dated informed consent to participate in the study.
• For patient under 18 years old: Tutor or person with parental authority must speak French and be able to give a signed and dated informed consent for the minor patient.
• Patients who are minors, whose DNA has been banked and for whom the parental authority has signed a consent form authorizing the subsequent use of this DNA for research purposes, including genetic analysis of cerebellar ataxias or associated pathologies, and for whom the RADIAL information sheet can be completed, are eligible.
• Patient affiliated to the French national health insurance
• \- For relatives:
• Male or female, over 18 years old (no upper age limit)
• Biological father or mother of a patient included in RADIAL-VALID research protocol
• Speaking and reading French, able to give a signed and dated informed consent to participate in the study
• Subject affiliated to the French national health insurance

You may not qualify if:

• \- For patients:
• Patient in whom targeted sequencing of a panel of PMDA genes and/or exome/genome sequencing have already been performed.
• For patients and related:
• Subject of a legal protection measure

Sponsors & Collaborators

• University Hospital, Strasbourg, France: lead

Study Sites (8)

CHU de Besancon- Neurology

Besançon, France

RECRUITING

CHU de Dijon- Neurology

Dijon, France

RECRUITING

CHU Lille- Neurology

Lille, France

NOT YET RECRUITING

CHU Marseille- Neurology

Marseille, France

RECRUITING

CHU Montpellier - Neurology

Montpellier, France

RECRUITING

CHU Nancy- Neurology

Nancy, France

RECRUITING

CHRU de Strasbourg - Neurology/Pediatrics

Strasbourg, France

RECRUITING

CHU Toulouse- Neurology

Toulouse, France

RECRUITING

Study Officials

• Tranchant Christine, MD

  CHRU Strasbourg

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Tranchant Christine, MD

CONTACT

+33 3 88 12 85 31; christine.tranchant@chru-strasbourg.fr

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 5, 2020
• First Posted: February 7, 2020
• Study Start: September 20, 2021
• Primary Completion (Estimated): September 1, 2029
• Study Completion (Estimated): September 1, 2029
• Last Updated: August 27, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

FR (8)