Diagnostic Research in Patients With Rare Diseases -Solving the Unsolved Rare Diseases

Rare Diseases Clinical Trial

— AnDDI-Solve-RD  

Official title:

Diagnostic Research in Patients With Rare Diseases -Solving the Unsolved Rare Diseases

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04024774
• Other study ID #: OLIVIER-FAIVRE H2020 2017
• Status: Recruiting
• Start date: November 14, 2019
• Est. completion date: November 2024

Study information

• Verified date: February 2024
• Source: Centre Hospitalier Universitaire Dijon
• Contact: Laurence OLIVIER-FAIVRE
• Phone: 03.80.29.53.13
• Email: laurence.faivre[@]chu-dijon.fr
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Most diagnostically unsolved rare disease have a genetic cause. These causes have not been found applying the current methodologies due to technical limitations (e.g. repeat expansions, changes in non-coding (intronic) regions) or, although methodically recorded, their pathophysiological significance but not classified as clinically relevant. A re- and meta-analysis of existing data sets with new algorithms and statistical models as well as the complementation with other omics technologies followed by functional follow-up studies in appropriate disease models (e.g. patient cell lines) allows to elucidate additional causes of diseases and improve the diagnosis of hereditary diseases. In addition to the direct examination of persons affected, the analysis of healthy family members, for example of parents, plays an important role in a so-called trio analysis, especially in the efficient filtering of the extensive data sets for newly created changes, so-called de novo- Variants (new mutations). In the context of the outlined analyzes, new disease genes can be found and validated. The gain of scientific knowledge due to a better understanding of basic cell biological mechanisms can contribute to the development of targeted therapeutic approaches.

In this context, the Solve-RD project has been built and financed by the European Union with the ambitions to solve large numbers of rare disease, for which a molecular cause is not known yet by sophisticated combined omics approaches, and to improve diagnostics of rare disease patients. Solve-RD fully integrates with the newly formed European Reference Networks (ERNs) for rare diseases, and in particular the ERN-RND, -EURO-NMD, -ITHACA, and -GENTURIS. The AnDDI-Rares network is fully affiliated to the ERN ITHACA network and will actively contribute to the project, by the ambition of sharing knowledge about genes, genomic variants and phenotypes.

The project will first reanalyse 18.000 negative exomes from the different ERNs performed in a diagnostic or research context (collection of biomaterial, clinical/phenotypic data plus next-generation sequencing has already been performed, and the patient/family has agreed previously in writing that their sample could be used for research related to their disease, with no study related presence required. The project will also propose new multi-omics analyses with new samples needed in 500 patients and their parents in total, justifying the AnDDI-Solve-RD project.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: November 2024
• Est. primary completion date: November 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

Inclusion Criteria:

• Persons or legal guardian who have given their written informed consent

• Unclear molecular cause of the disease corresponding to the list of diseases selected by the Solve-RD data interpretation force (principal investigator part of the team)

• Suspected genetic cause of the disease with negative exome reanalysis

• Healthy parents available for trio analysis

Exclusion Criteria:

• Person not affiliated to a national health insurance scheme

Related Conditions & MeSH terms

• Rare Diseases

Intervention

Biological:
• Biological samples
blood samples, urine samples, tissue samples

Genetic:
• Genetic test
anamnesis and NGS sequencing

Locations

Country	Name	City	State
France	CHU de Dijon	Dijon

Sponsors (1)

Lead Sponsor	Collaborator
Centre Hospitalier Universitaire Dijon

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Molecular genetic	Verification of the genetic causes of unclear genetic diseases	Day 1
Secondary	Number of diagnoses	Improve number of diagnoses of unclear syndromes	Day 1
Secondary	Characterization of gene defects	Further characterization of the identified gene defects	Day 1
Secondary	Number of patients receiving appropriate therapy after successful diagnosis		Day 1