Validation of a diagnostic algorithm for autosomal recessive cerebellar ataxia

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

This study tests a new tool that helps doctors diagnose a rare condition called autosomal recessive cerebellar ataxia more accurately by looking at different patient features.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 400 (estimated)
• Ages: 5 Years and up
• Sex: All
• Sponsor: University Hospital, Strasbourg, France (Academic / other)
• Locations: 8 sites (Besançon and 7 other locations)
• Trial ID: NCT04261127 on ClinicalTrials.gov

What this trial studies

The RADIAL algorithm is designed to improve the diagnosis of autosomal recessive cerebellar ataxia (ARCA) by analyzing clinical and paraclinical features of patients. It assigns prediction scores based on a comprehensive review of 67 ARCA types, allowing for a ranking of possible diagnoses. The algorithm's performance was validated using a multinational cohort of 834 patients with confirmed ARCA, achieving high sensitivity and specificity rates. This approach aims to enhance diagnostic accuracy and facilitate timely treatment decisions for affected individuals.

Who should consider this trial

Good fit: Ideal candidates include individuals over 5 years old with cerebellar ataxia onset before age 40 and a family history suggesting autosomal recessive inheritance.

Not a fit: Patients with a known genetic diagnosis of cerebellar ataxia or those with acquired causes of ataxia may not benefit from this study.

Why it matters

Potential benefit: If successful, this algorithm could significantly improve the accuracy of diagnosing autosomal recessive cerebellar ataxia, leading to better patient management and treatment options.

How similar studies have performed: Other studies have shown promising results with similar diagnostic algorithms, indicating potential for success in this approach.

Eligibility criteria

Inclusion Criteria:

\- For patients:

1. Patient, male or female, over 5 years old (no upper age limit)
2. Patient with cerebellar ataxia who started before the age of 40
3. Patient with a family history compatible with autosomal recessive inheritance (sporadic case, consanguinity, several cases in siblings)
4. Patient in which an acquired cause of cerebellar ataxia has been excluded
5. Patient whose genetic diagnosis is unknown (NB: patients with a known negative result for the Friedreich's disease gene are eligible for inclusion))
6. 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.

   Patients who have reached the age of majority and whose DNA has been banked and who have 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 in full, are eligible for inclusion.
7. 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.
8. Patient affiliated to the French national health insurance

   \- For relatives:
9. Male or female, over 18 years old (no upper age limit)
10. Biological father or mother of a patient included in RADIAL-VALID research protocol
11. (for prospective inclusion only) To be available for a visit to the participating center where the child is being followed
12. Speaking and reading French, able to give a signed and dated informed consent to participate in the study
13. Subject affiliated to the French national health insurance

    Exclusion Criteria:

    \- For patients:
14. Patient in whom targeted sequencing of a panel of PMDA genes and/or exome/genome sequencing have already been performed.

    * For patients and related:
15. Subject of a legal protection measure
16. Subject in exclusion period (determined by previous or current study)

Where this trial is running

Besançon and 7 other locations

• 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 contacts

• Principal investigator: Tranchant Christine, MD — CHRU Strasbourg
• Study coordinator: Tranchant Christine, MD

Conditions Autosomal Recessive Cerebellar Ataxia; autosomal recessive cerebellar ataxia; algorithm; genetic diagnosis