Initiative for Clinical Long-read Sequencing

NCT06060184 | Not Yet Recruiting

• 1 other identifier: IonGER
• Study Type: interventional
• Target: 500
• Locations: 1 country
• Sites: 1

Brief Summary

The study aims to comprehensively introduce Long-read Genome sequencing (LR-GS) based genetic testing into clinical routine. In order to demonstrate the superiority of untargeted LR-GS over Short-read Genome sequencing (SR-GS) to establish firm genetic diagnoses, the investigators will rely on a multi-center "Translate Nationale Aktionsbündnis für Menschen mit Seltenen Erkrankungen" (Translate National Action Alliance for People with Rare Diseases Germany, TNAMSE) cohort of unsolved patients with neurological, neurodevelopmental, and imprinting disorders that is expectedly enriched for complex genomic variation. Within the framework of genomDE, the investigators will then implement, for the first time, LR-GS in the diagnostic work-up of a prospective cohort of patients with a broad range of clinical indications including rare diseases and cancer predisposition.

Conditions

Genetic Predisposition

Keywords

Long-read sequencing; Rare diseases; Cancer preposition; Translate-NAMSE; German initiative for genomic medicine (genomDE)

Outcome Measures

Primary Outcomes (1)

• Number of patients with Rare Disease (RD) or cancer predisposition syndromes with confirmed diagnosis by LR-GS compared to previous diagnostic methods including SR-GS

  A molecular diagnosis is considered confirmed when likely pathogenic or pathogenic variants are identified according to the American College of Medical Genetics and Genomics (ACMG). classification.

  Day 1

Study Arms (2)

Retrospective cohort

EXPERIMENTAL

Subjects with unclear molecular cause of the disease. The subjects are clinically characterized in the context of outpatient/ inpatient standard care at the University Hospital Tübingen (UKT) or cooperating locations.

Genetic: Next-Generation Sequencing (NGS)

Prospective cohort

EXPERIMENTAL

Subjects with indication for genome diagnostics (e.g. within the initiative for genomic medicine (genomDE) based on §64e German Social Code (SGB) Fifth Book (V) (SGB V).

Genetic: Next-Generation Sequencing (NGS)

Interventions

Next-Generation Sequencing (NGS) GENETIC

Sequencing of genomes (Long read NGS)

Prospective cohort; Retrospective cohort

Eligibility Criteria

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

You may qualify if:

• Unclear molecular cause of the disease (retrospective cohort)
• Indication for genome diagnostics (prospective cohort; e.g. within the initiative for genomic medicine (genomDE) based on §64e SGB V)
• Suspected genetic cause of the disease

You may not qualify if:

• \- Missing informed consent of the patient or legal guardian

Sponsors & Collaborators

• University Hospital Tuebingen: lead
• RWTH Aachen University: collaborator
• Medical University of Hannover: collaborator
• Charite University, Berlin, Germany: collaborator

Study Sites (1)

University Hospital Tübingen

Tübingen, 72076, Germany

Location

MeSH Terms

Conditions

Genetic Predisposition to Disease; Rare Diseases

Interventions

High-Throughput Nucleotide Sequencing

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Sequence Analysis; Genetic Techniques; Investigative Techniques

Study Officials

• Tobias Haack, Dr. med.

  University Hospital Tübingen

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Tobias Haack, Dr.

CONTACT

+49 7071 29; tobias.haack@med.uni-tuebingen.de

Olaf Rieß, Prof. Dr.

CONTACT

+49 7071 29; olaf.riess@med.uni-tuebingen.de

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Parallel Assignment

Study Record Dates

• First Submitted: September 13, 2023
• First Posted: September 29, 2023
• Study Start: December 1, 2023
• Primary Completion: December 1, 2025
• Study Completion (Estimated): December 1, 2026
• Last Updated: September 29, 2023

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: ANALYTIC CODE
• Time Frame: Data will become available after analysis and unlimited.

Locations

DE (1)