Genetic PredispositionIonGERNCT06060184
Initiative for Clinical Long-read Sequencing
A study testing Next-Generation Sequencing (NGS) in people with Genetic Predisposition, run by University Hospital Tuebingen at 1 site in Germany.
Trial 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… Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Genetic Predisposition
- What is being tested?
- Next-Generation Sequencing (NGS)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 500 participants
- Where
- 1 siteGermany
- Study dates
- 1 Dec 2023to 1 Dec 2026
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
Who cannot join
- Missing informed consent of the patient or legal guardian
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Germany1 site
University Hospital Tübingen
Tübingen, 72076
Tobias Haack, Dr., +49 7071 29 ext. 77696, tobias.haack@med.uni-tuebingen.de
Rieß, Prof. Dr., +49 7071 29 ext. 72288, olaf.riess@med.uni-tuebingen.de
About this study
Official title: Initiative for Clinical Long-read Sequencing - Towards Implementation of Long-read Genome Sequencing in Routine Diagnostics
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.
Read the detailed description
The proposed study aims to develop a blueprint for the implementation of LR-GS in clinical diagnostics. Hence Standard Operating Procedures (SOPs) and guidelines for library preparation, bioinformatic analysis, and clinical interpretation will be compiled. Furthermore, the investigators intend to develop an open source 'gold standard' bioinformatics pipeline, addressing all relevant types of genomic alterations, thus providing the bioinformatic basis for a streamlined implementation of LR-GS at other sites. In addition to in-depth phenotype information the availability of SR-GS will be instrumental to benchmark the ability to detect different types of genomic variation. Additional relevant issues for genetic testing such as variant calling in difficult-to-map genomic regions, detection of genomic methylation patterns, characterization of repeat expansion and duplicated genes, and haplotype-phased genome de novo assembly will be addressed. Moreover, based on the strong background in Artificial Intelligence (AI) driven variant prioritization in the consortium, the investigators aim to implement and/or develop tools that enable an efficient prioritization of disease-causing variants. Beyond the usage within the context of the proposed study, generated datasets will be made available according to the Findable, Accessible, Interoperable and Reusable (FAIR) principles for national (German Human Genome-Phenome Archive, GHGA) and international (European Genome-Phenome Archive, EGA, Genome-Phenome Analysis Platform, GPaP) data repositories. the investigators aim to establish a population scale reference dataset for Structural variants (SV), which is absolutely mandatory in the context of rare disease diagnostics.
- Conditions
- Genetic Predisposition
- Being tested
- Next-Generation Sequencing (NGS)
- Keywords
- Long-read sequencing, Rare diseases, Cancer preposition, Translate-NAMSE, German initiative for genomic medicine (genomDE)
- Medical subject headings
- Genetic Predisposition to Disease, Rare Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Next-Generation Sequencing (NGS)Genetic
Sequencing of genomes (Long read NGS)
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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). Receives: Genetic: Next-Generation Sequencing (NGS) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Day 1
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Sep 2023
- Study start1 Dec 2023 (estimated)
- Primary completion1 Dec 2025 (estimated)
- Study completion1 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Genetic PredispositionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- Parallel Assignment
- Masking
- None (open label)
- Enrolment
- 500 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Hospital Tuebingen
- Sponsor type
- University, hospital or other
- Collaborators
- RWTH Aachen University, Medical University of Hannover, Charite University, Berlin, Germany
- Responsible party
- Sponsor
- Investigators
- Tobias Haack, Dr. med., Principal investigator, University Hospital Tuebingen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06060184
- Sponsor's protocol ID
- IonGER
- Acronym
- IonGER
- Status last verified
- Sep 2023
- First submitted
- 13 Sep 2023
- Last updated
- 29 Sep 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: The IonGER study will provide data in a pseudonymised manner to national and international databases set up to increase the diagnostic yield through advanced analysis tools and matchmaking against other cohorts
Study at a glance
From the registry record, last updated by the sponsor on 29 Sep 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Initiative for Clinical Long-read Sequencing - Towards Implementation of Long-read Genome Sequencing in Routine Diagnostics
- ClinicalTrials.gov ID
- NCT06060184
- Acronym / sponsor ID
- IonGER / IonGER
- Conditions
- Genetic Predisposition
- Keywords
- Long-read sequencing, Rare diseases, Cancer preposition, Translate-NAMSE, German initiative for genomic medicine (genomDE)
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 500 participants (estimated)
- Lead sponsor
- University Hospital TuebingenUniversity, hospital or other
- Collaborators
- RWTH Aachen University, Medical University of Hannover, Charite University, Berlin, Germany
- Study start
- 1 Dec 2023 (estimated)
- Primary completion
- 1 Dec 2025 (estimated)
- Study completion
- 1 Dec 2026 (estimated)
- First posted
- 29 Sep 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
The proposed study aims to develop a blueprint for the implementation of LR-GS in clinical diagnostics. Hence Standard Operating Procedures (SOPs) and guidelines for library preparation, bioinformatic analysis, and clinical interpretation will be compiled. Furthermore, the investigators intend to develop an open source 'gold standard' bioinformatics pipeline, addressing all relevant types of genomic alterations, thus providing the bioinformatic basis for a streamlined implementation of LR-GS at other sites. In addition to in-depth phenotype information the availability of SR-GS will be instrumental to benchmark the ability to detect different types of genomic variation. Additional relevant issues for genetic testing such as variant calling in difficult-to-map genomic regions, detection of genomic methylation patterns, characterization of repeat expansion and duplicated genes, and haplotype-phased genome de novo assembly will be addressed. Moreover, based on the strong background in Artificial Intelligence (AI) driven variant prioritization in the consortium, the investigators aim to implement and/or develop tools that enable an efficient prioritization of disease-causing variants. Beyond the usage within the context of the proposed study, generated datasets will be made available according to the Findable, Accessible, Interoperable and Reusable (FAIR) principles for national (German Human Genome-Phenome Archive, GHGA) and international (European Genome-Phenome Archive, EGA, Genome-Phenome Analysis Platform, GPaP) data repositories. the investigators aim to establish a population scale reference dataset for Structural variants (SV), which is absolutely mandatory in the context of rare disease diagnostics.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Parallel Assignment
| Arm | Type | Receives |
|---|---|---|
| Retrospective cohort | Experimental | Genetic: Next-Generation Sequencing (NGS)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. |
| Prospective cohort | Experimental | Genetic: Next-Generation Sequencing (NGS)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). |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (1 listed)
- Missing informed consent of the patient or legal guardian
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Next-Generation Sequencing (NGS)Sequencing of genomes (Long read NGS) | Genetic | Prospective cohort, Retrospective cohort |
Primary outcome
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
Time frame: Day 1
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.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Sep 2023.
- Individual participant dataSharing planned: Yes. The IonGER study will provide data in a pseudonymised manner to national and international databases set up to increase the diagnostic yield through advanced analysis tools and matchmaking against other cohorts
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Tobias Haack, Dr. med. principal investigator
University Hospital Tuebingen
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Next-Generation Sequencing (NGS) in people with Genetic Predisposition, run by University Hospital Tuebingen at 1 site in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 29 Sep 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Tobias Haack, Dr. (+49 7071 29 ext. 77696, tobias.haack@med.uni-tuebingen.de), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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 (time frame: Day 1). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Sep 2023.