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

NCT04024774 | Recruiting

• 1 other identifier: OLIVIER-FAIVRE H2020 2017
• Study Type: observational
• Target: 50
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Rare Diseases

Outcome Measures

Primary Outcomes (1)

• Molecular genetic

  Verification of the genetic causes of unclear genetic diseases

  Day 1

Secondary Outcomes (3)

• Number of diagnoses

  Day 1

• Characterization of gene defects

  Day 1

• Number of patients receiving appropriate therapy after successful diagnosis

  Day 1

Study Arms (1)

index cases and their parents

Biological: Biological samples; Genetic: Genetic test

Interventions

Biological samples BIOLOGICAL

blood samples, urine samples, tissue samples

index cases and their parents

Genetic test GENETIC

anamnesis and NGS sequencing

index cases and their parents

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients with rare diseases

You may qualify if:

• 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

You may not qualify if:

• Person not affiliated to a national health insurance scheme

Sponsors & Collaborators

• Centre Hospitalier Universitaire Dijon: lead

Study Sites (1)

CHU de Dijon

Dijon, 21079, France

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

Blood sample

MeSH Terms

Conditions

Rare Diseases

Interventions

Genetic Testing

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Genetic Techniques; Genetic Services; Health Services; Health Care Facilities Workforce and Services; Diagnostic Services; Preventive Health Services

Central Study Contacts

Laurence OLIVIER-FAIVRE

CONTACT

03.80.29.53.13; laurence.faivre@chu-dijon.fr

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 17, 2019
• First Posted: July 18, 2019
• Study Start: November 14, 2019
• Primary Completion: May 1, 2026
• Study Completion: May 1, 2026
• Last Updated: April 2, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)