Use of Omics Methods to Classify Variations of Uncertain Significance and Improve Diagnosis of Neurogenetic Diseases

NCT06955624 | Recruiting

• 2 other identifiers: 2024/0190/HP2024-A01559-38
• Study Type: interventional
• Target: 95
• Locations: 1 country
• Sites: 1

Brief Summary

Many neurological disorders show a strong genetic basis, from hereditary diseases caused by a single mutation in a given gene, to diseases caused by combinations of strong genetic risk factors. However, even after the sequencing of the appropriate genes, a large proportion of patients remains undiagnosed, either because there is no candidate mutation observed, or in case of identification of a candidate mutation with insufficient knowledge to consider it as pathogenic or not. The aim of this project is to identify the cause of neurogenetic diseases in patients in situations of diagnostic wandering or dead ends by proposing the analysis of RNA and/or proteins from different tissues.

Conditions

Neurogenetic Diseases

Keywords

Neurogenetic diseases; Central nervous system disease

Outcome Measures

Primary Outcomes (1)

• number and proportion of patients

  number and proportion of patients in the "Patients with inconclusive results" group for whom a final diagnosis can be made at the end of this research.

  through study completion, an average of 5 years

Secondary Outcomes (2)

• Inclusion

  through study completion, an average of 5 years

• Identification of at least one candidate biomarker linked to one or more abnormalities of a gene or group of genes.

  through study completion, an average of 5 years

Study Arms (1)

Controls

OTHER

* Patients with neurological disease affecting the central nervous system, of confirmed monogenic or probable oligogenic cause (positive controls * Unaffected relatives, showing no symptoms of the disease after the expected age of onset of symptoms in the family

Genetic: RNA and/or DNA methylation and/or protein analysis

Interventions

RNA and/or DNA methylation and/or protein analysis GENETIC

RNA and/or DNA methylation and/or protein analysis from a blood sample or another tissue including dedifferenciation into induced pluripotent stem cells

Controls

Eligibility Criteria

• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• a. Patient, major or minor, with a neurological disease affecting the central nervous system, who has already benefited from a genomic analysis (panel, exome or genome sequencing) as part of routine care, with inconclusive analysis because the result was either a variation of uncertain significance or the absence of a variant of interest (patients with inconclusive genomic results).
• b. Patient with neurological disease affecting the central nervous system, of confirmed monogenic or probable oligogenic cause (positive controls).
• A relative of a type 1a. or 1b. patient with no symptoms of the disease, after the expected age of onset of symptoms in the patient's own family (healthy relatives).
• For all 3 groups:
• Affiliation with a social security scheme
• Agreement to take part in the study with signature of a specific informed consent form for the study.

You may not qualify if:

• For patients with inconclusive results: Patient with a neurological disease not suspected of a monogenic or oligogenic cause
• For healthy relatives: existence of a neurological disease (other than uncomplicated migraine) or psychiatric disease (other than simple anxiety stable under treatment).

Sponsors & Collaborators

• University Hospital, Rouen: lead
• University Hospital, Lille: collaborator
• Groupe Hospitalier Pitie-Salpetriere: collaborator

Study Sites (1)

Rouen University Hospital

Rouen, France

RECRUITING

MeSH Terms

Conditions

Central Nervous System Diseases

Condition Hierarchy (Ancestors)

Nervous System Diseases

Central Study Contacts

Gaël Nicolas, MD, PhD

CONTACT

0033232888747; gael.nicolas@chu-rouen.fr

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Qualification: Category 2 Product or procedure: excluding health products (products not mentioned in Article L.5311-11 of the Public Health Code)

Study Record Dates

• First Submitted: April 15, 2025
• First Posted: May 2, 2025
• Study Start: January 15, 2025
• Primary Completion (Estimated): January 15, 2030
• Study Completion (Estimated): January 15, 2031
• Last Updated: May 2, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)