Validation of the RADIAL Algorithm for Diagnosis of Autosomal Recessive Cerebellar Ataxia
Trial statusRecruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexAll
Age5+
SponsorUniversity Hospital, Strasbourg, France
About this trial
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.
Eligibility criteria
This trial accepts healthy volunteersQualifiers
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
Disqualifiers
Patient in whom targeted sequencing of a panel of PMDA genes and/or exome/genome sequencing have already been performed.
Subject of a legal protection measure
Subject in exclusion period (determined by previous or current study)
Trial design
Design model
Single group
Treatments tested in this trial
Genetic diagnosis (PMDA panel)
GeneticBlood samples for DNA study
Use of RADIAL algorithm
Diagnostic testRADIAL card filling (contains clinical and biological data)
Treatment groups
400 Participants
are divided into 1 treatment groupGroup A: experimental armExperimental treatment 2 interventions
Trial outcomes
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.
Time frame
At final visit (depending of genetic results from 2 to 24 month maximum after inclusion visit)Secondary outcomes
1
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).
Time frame
At final visit (depending of genetic results from 2 to 24 month maximum after inclusion visit)2
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.
Time frame
At final visit (depending of genetic results from 2 to 24 month maximum after inclusion visit)3
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.
Time frame
At final visit (depending of genetic results from 2 to 24 month maximum after inclusion visit)4
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.
Time frame
At final visit (depending of genetic results from 2 to 24 month maximum after inclusion visit)Sponsors and contacts
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Source ClinicalTrials.gov