Use of Omics Methods to Classify Variations of Uncertain Significance and Improve Diagnosis of Neurogenetic Diseases (OMID-NEURO)

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.

Study Overview

• Status: Recruiting
• Conditions: Neurogenetic Diseases
• Intervention / Treatment: Genetic: RNA and/or DNA methylation and/or protein analysis

• Study Type: Interventional
• Enrollment (Estimated): 95
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Gaël Nicolas, MD, PhD; Phone Number: 0033232888747; Email: gael.nicolas@chu-rouen.fr

Study Locations

• France
  • Rouen, France
    • Recruiting
    • Rouen University Hospital
    • Contact: Gaël NICOLAS; Phone Number: 0033232888747; Email: gael.nicolas@chu-rouen.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

For this project, the inclusion of 3 participant profiles is required:

• 1a. 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).
• 1b. 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.

Exclusion Criteria:

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).

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Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Controls; 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; RNA and/or DNA methylation and/or protein analysis from a blood sample or another tissue including dedifferenciation into induced pluripotent stem cells

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Inclusion	Inclusion of at least 50 participants with successful implementation of at least two procedures (see below, list of procedures)	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.	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

Collaborators and Investigators

• Sponsor: University Hospital, Rouen
• Collaborators: University Hospital, Lille; Groupe Hospitalier Pitie-Salpetriere

Study record dates

Study Major Dates

• Study Start (Actual): January 15, 2025
• Primary Completion (Estimated): January 15, 2030
• Study Completion (Estimated): January 15, 2031

Study Registration Dates

• First Submitted: April 15, 2025
• First Submitted That Met QC Criteria: April 24, 2025
• First Posted (Actual): May 2, 2025

Study Record Updates

• Last Update Posted (Actual): May 2, 2025
• Last Update Submitted That Met QC Criteria: April 24, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: Central nervous system disease; Neurogenetic diseases
• Other Study ID Numbers: 2024/0190/HP; 2024-A01559-38 (Registry Identifier: RCB)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No