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Validation of the RADIAL Algorithm for Diagnosis of Autosomal Recessive Cerebellar Ataxia (RADIAL-VALID)

Primary Purpose

Autosomal Recessive Cerebellar Ataxia

Status

Recruiting

Phase

Not Applicable

Locations

France

Study Type

Interventional

Intervention

Genetic diagnosis (PMDA panel)

Use of RADIAL algorithm

About this trial

This is an interventional diagnostic trial for Autosomal Recessive Cerebellar Ataxia focused on measuring autosomal recessive cerebellar ataxia, algorithm, genetic diagnosis

Eligibility Criteria

5 Years - undefined (Child, Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

- 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
Patient whose genetic diagnosis is unknown
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 for less than 2 years 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.
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 for less than 2 years, 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 in full, 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
To be available for a visit to the participating center where the child is being followed
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

Exclusion Criteria:

For patients and related
1. Person deprived of liberty by an administrative or judicial decision
2. Person under legal protection measure (guardianship, guardianship or court order)
3. Subject in exclusion period (determined by previous or current study)

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

experimental arm

Arm Description

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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).

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.

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

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

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.

Full Information

NCT ID

NCT04261127

First Posted

February 5, 2020

Last Updated

October 20, 2023

Sponsor

University Hospital, Strasbourg, France

1. Study Identification

Unique Protocol Identification Number

NCT04261127

Brief Title

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

Acronym

RADIAL-VALID

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

October 2023

Overall Recruitment Status

Recruiting

Study Start Date

September 20, 2021 (Actual)

Primary Completion Date

September 2029 (Anticipated)

Study Completion Date

September 2029 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University Hospital, Strasbourg, France

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Autosomal Recessive Cerebellar Ataxia

Keywords

autosomal recessive cerebellar ataxia, algorithm, genetic diagnosis

7. Study Design

Primary Purpose

Diagnostic

Study Phase

Not Applicable

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

400 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

experimental arm

Arm Type

Experimental

Arm Description

Intervention Type

Genetic

Intervention Name(s)

Genetic diagnosis (PMDA panel)

Intervention Description

Blood samples for DNA study

Intervention Type

Diagnostic Test

Intervention Name(s)

Use of RADIAL algorithm

Intervention Description

RADIAL card filling (contains clinical and biological data)

Primary Outcome Measure Information:

Title

Description

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 Outcome Measure Information:

Title

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)

Title

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

Description

Time Frame

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

Title

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

Description

Time Frame

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

Title

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

Description

Time Frame

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

Title

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

Description

Time Frame

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

10. Eligibility

Sex

All

Minimum Age & Unit of Time

5 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: - 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 Patient whose genetic diagnosis is unknown (NB: patients with a known negative result for the Friedreich's disease gene are eligible for inclusion)) 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. 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 (for prospective inclusion only) To be available for a visit to the participating center where the child is being followed 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 Exclusion Criteria: - 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 Subject in exclusion period (determined by previous or current study)

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Tranchant Christine, MD

Phone

+33 3 88 12 85 31

christine.tranchant@chru-strasbourg.fr

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Tranchant Christine, MD

Organizational Affiliation

CHRU Strasbourg

Official's Role

Principal Investigator

Facility Information:

Facility Name

CHU de Besancon- Neurology

City

Besançon

Country

France

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Bereau Matthieu, MD

Phone

+33381668166

mbereau@chu-besancon.fr

First Name & Middle Initial & Last Name & Degree

Bereau Matthieu, MD

Facility Name

CHU de Dijon- Neurology

City

Dijon

Country

France

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Moreau Thibault, MD

Phone

+33380471248

Thibault.moreau@chu-dijon.fr

First Name & Middle Initial & Last Name & Degree

Quentin Thomas, MD

First Name & Middle Initial & Last Name & Degree

Christel Thauvin, MD PhD

First Name & Middle Initial & Last Name & Degree

Laurence Faivre, MD PhD

First Name & Middle Initial & Last Name & Degree

Gwendoline Dupont, MD

First Name & Middle Initial & Last Name & Degree

Vincent Schneider, MD

Facility Name

CHU Lille- Neurology

City

Lille

Country

France

Individual Site Status

Not yet recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Devos David, MD

David.DEVOS@CHRU-LILLE.FR

First Name & Middle Initial & Last Name & Degree

David Devos, MD

First Name & Middle Initial & Last Name & Degree

Eugénie MUTEZ, MD

Facility Name

CHU Marseille- Neurology

City

Marseille

Country

France

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Azulay Jean-Philippe, MD

Phone

+33 491380000

jean-philippe.azulay@ap-hm.fr

First Name & Middle Initial & Last Name & Degree

Azulay Jean-Philippe, MD

Facility Name

CHU Montpellier - Neurology

City

Montpellier

Country

France

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Marelli Cecilia, MD

Phone

+33 467336733

cecilia.marelli@upmc.fr

First Name & Middle Initial & Last Name & Degree

Marelli Cecilia, MD

First Name & Middle Initial & Last Name & Degree

Roubertie Agathe, MD

Facility Name

CHU Nancy- Neurology

City

Nancy

Country

France

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Renaud Mathilde, MD

Phone

+33383154500

m.renaud@chru-nancy.fr

First Name & Middle Initial & Last Name & Degree

Renaud Mathilde, MD

First Name & Middle Initial & Last Name & Degree

Fismand Solène, MD

Facility Name

CHRU de Strasbourg - Neurology/Pediatrics

City

Strasbourg

Country

France

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Tranchant Christine, MD

Phone

+33388128531

christine.tranchant@chru-strasbourg.fr

First Name & Middle Initial & Last Name & Degree

Anheim Mathieu, MD

Phone

+33388128535

mathieu.anheim@chru-strasbourg.fr

First Name & Middle Initial & Last Name & Degree

Laugel Vincent, MD PhD

First Name & Middle Initial & Last Name & Degree

Spitz Marie Aude, MD

First Name & Middle Initial & Last Name & Degree

De Saint Martin Anne, MD

First Name & Middle Initial & Last Name & Degree

Abi Warde Marie Thérèse, MD

First Name & Middle Initial & Last Name & Degree

Iosif Andra Valentina, MD

First Name & Middle Initial & Last Name & Degree

Wirth Thomas, MD

First Name & Middle Initial & Last Name & Degree

Tranchant Christine, MD PhD

First Name & Middle Initial & Last Name & Degree

Anheim Mathieu, MD PhD

Facility Name

CHU Toulouse- Neurology

City

Toulouse

Country

France

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Ory-Magne Fabienne, MD

Phone

+33 561772233

ory.f@chu-toulouse.fr

First Name & Middle Initial & Last Name & Degree

Ory-Magne Fabienne, MD

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

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

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Validation of the RADIAL Algorithm for Diagnosis of Autosomal Recessive Cerebellar Ataxia (RADIAL-VALID)

Autosomal Recessive Cerebellar Ataxia

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial