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

Autosomal Recessive Cerebellar Ataxia Clinical Trial

— RADIAL-VALID  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04261127
• Other study ID #: 7346
• Status: Recruiting
• Phase: N/A
• Start date: September 20, 2021
• Est. completion date: September 2029

Study information

• Verified date: October 2023
• Source: University Hospital, Strasbourg, France
• Contact: Tranchant Christine, MD
• Phone: +33 3 88 12 85 31
• Email: christine.tranchant[@]chru-strasbourg.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 400
• Est. completion date: September 2029
• Est. primary completion date: September 2029
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 5 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Ataxia
• Autosomal Recessive Cerebellar Ataxia
• Cerebellar Ataxia

Intervention

Genetic:
• Genetic diagnosis (PMDA panel)
Blood samples for DNA study

Diagnostic Test:
• Use of RADIAL algorithm
RADIAL card filling (contains clinical and biological data)

Locations

Country	Name	City	State
France	CHU de Besancon- Neurology	Besançon
France	CHU de Dijon- Neurology	Dijon
France	CHU Lille- Neurology	Lille
France	CHU Marseille- Neurology	Marseille
France	CHU Montpellier - Neurology	Montpellier
France	CHU Nancy- Neurology	Nancy
France	CHRU de Strasbourg - Neurology/Pediatrics	Strasbourg
France	CHU Toulouse- Neurology	Toulouse

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Strasbourg, France

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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)
Secondary	Comparison of interpretation times by the clinical-genetic team (genetic and clinical data) with and without the help of the RADIAL algorithm	Randomization is a methodological refinement that is only useful for this secondary endpoint (does not relate to the primary endpoint). The clinical and paraclinical data of all patients will be treated in the same way, and randomization concerns only the use of RADIAL made by the data biologist in sample processing. There is therefore no randomization of subjects but only of genetic results.; At the genetic study stage (Panel PMDA panel), for the patient group randomized "with RADIAL results", the interpretation of genetic data (and in particular of the different variants found) will be done aware of the results given by RADIAL, and in the randomized group "without results RADIAL ", the analysis of the genetic data will be done in the absence of knowledge of the results provided by RADIAL.	At final visit (depending of genetic results from 2 to 24 month maximum after inclusion visit)
Secondary	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	Randomization is a methodological refinement that is only useful for this secondary endpoint (does not relate to the primary endpoint). The clinical and paraclinical data of all patients will be treated in the same way, and randomization concerns only the use of RADIAL made by the data biologist in sample processing. There is therefore no randomization of subjects but only of genetic results.; At the genetic study stage (Panel PMDA panel), for the patient group randomized "with RADIAL results", the interpretation of genetic data (and in particular of the different variants found) will be done aware of the results given by RADIAL, and in the randomized group "without results RADIAL ", the analysis of the genetic data will be done in the absence of knowledge of the results provided by RADIAL.	At final visit (depending of genetic results from 2 to 24 month maximum after inclusion visit)
Secondary	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	Randomization is a methodological refinement that is only useful for this secondary endpoint (does not relate to the primary endpoint). The clinical and paraclinical data of all patients will be treated in the same way, and randomization concerns only the use of RADIAL made by the data biologist in sample processing. There is therefore no randomization of subjects but only of genetic results.; At the genetic study stage (Panel PMDA panel), for the patient group randomized "with RADIAL results", the interpretation of genetic data (and in particular of the different variants found) will be done aware of the results given by RADIAL, and in the randomized group "without results RADIAL ", the analysis of the genetic data will be done in the absence of knowledge of the results provided by RADIAL.	At final visit (depending of genetic results from 2 to 24 month maximum after inclusion visit)
Secondary	Percentage of patients for whom the genome analysis will have detected a new gene.	If no diagnosis is established after the PMDA + RADIAL analyzes, additional genetic analyzes will be carried out for patient and for relatives (genome). These new analyzes should help to define the diagnosis of the patient.	At final visit (depending of genetic results from 2 to 24 month maximum after inclusion visit)