Identification of the Genetic Causes of Rare Diseases With Negative Exome Findings

Rare Diseases Clinical Trial

Official title:

Identification of the Genetic Causes of Rare Diseases With Negative Exome Findings

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04315727
• Other study ID #: GENOME +
• Status: Recruiting
• Phase: N/A
• Start date: February 1, 2021
• Est. completion date: December 2024

Study information

• Verified date: November 2023
• Source: University Hospital Tuebingen
• Contact: Olaf Rieß, Prof. Dr.
• Phone: +49 7071 29
• Email: olaf.riess[@]med.uni-tuebingen.de
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The GENOME + project will enroll patients (n = ca. 100) and their healthy parents with unclear molecular cause of the disease, suspected genetic cause of the disease and previous detailed molecular analysis like Whole Exome Sequencing (WES) did not lead to the identification of the disease causing mechanism. As well healthy parents of those affected for trio analysis (exception of one parent is not available for the study).

Description:

In the GENOME+ study (monocentric, prospective, open-label diagnostic study), patients with molecularly undiagnosed diseases will diagnostically be analyzed by means of omics technologies or re-analyzed using existing datasets. The following questions will be leading the study:

Primary:

• Identification of the molecular causes of unclear rare diseases

Secondary:

• Improve number of diagnoses for patients with rare diseases

• Further characterization of the identified putative disease causes

• Increase number of patients receiving appropriate therapy after successful diagnosis.

In addition, healthy parents of the subjects may be included in the study to perform parent-child (trio) analyses.

In addition, phenotype and omics data will be shared within the University Hospital Tübingen, Germany and with external collaborators to improve the diagnostic rate of the patients included in the study.

Storage of blood or tissue samples is not primary goal of this project, but may be necessary for further analyses.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: December 2024
• Est. primary completion date: July 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

Inclusion Criteria:

• Unclear diagnosis

• Suspected genetic cause of the disease

• Previous detailed molecular analysis like Whole Exome Sequencing (WES) did not lead to the identification of the disease causing mechanism

• Healthy parents of those affected for trio analysis (exception of one parent is not available for the study)

Exclusion Criteria:

• Missing informed consent of the patient and her/his parents

Related Conditions & MeSH terms

• Disease Susceptibility
• Genetic Predisposition to Disease
• Rare Diseases

Intervention

Genetic:
• WGS Diagnostic Blood take for genetic diagnostic.
Blood sampling, shot clinical characterization, WGS based trio sequencing, NGS analysis and other omics analysis (transcriptomics, proteomics, metabolomics), functional cell biology studies (for example in fibroblast cultures), RNA Sequencing (RNA-seq).
• Hair collection
Hair including root will be collected from the scalp (~15-20) and transferred to cultivation medium for the organoid cultivation

Locations

Country	Name	City	State
Germany	University Hospital Tübingen	Tübingen
Germany	University Hospital Tübingen	Tübingen

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital Tuebingen

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Identification of the molecular causes of unclear rare diseases	Number of molecular causes	Day 1
Secondary	Diagnoses for patients with rare diseases	Number of diagnoses for patients with rare diseases	Day 1
Secondary	Molecular characterization of putative disease causes	Identify molecular characterization of the putative disease causes	Day 1
Secondary	Patients receiving appropriate therapy after successful diagnosis	Number of patients receiving appropriate therapy after successful diagnosis	Day 1