Rare DiseasesNCT03954652
Whole Genome Trio Sequencing as a Standard Routine Test in Patients With Rare Diseases - "GENOME FIRST APPROACH"
A study testing WGS-Diagnostic in people with Rare Diseases and Genetic Predisposition, run by University Hospital Tuebingen at 1 site in Germany.
Trial summary
The GENOME FIRST APPROACH project will enroll patients (n = 450) and their healthy parents with unclear molecular cause of the disease, suspected genetic cause of the disease and the healthy parents of those affected for trio analysis (N in total 1350). Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Rare Diseases, Genetic Predisposition
- What is being tested?
- WGS-Diagnostic
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,350 participants
- Where
- 1 siteGermany
- Study dates
- 1 Oct 2019to 1 Oct 2022
- Phase
- Interventional
- Are there results?
- None posted in the registry
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
- Suspected genetic cause of the disease
- Healthy parents of those affected for trio analysis Cohort 1: IQ < 70 with and without malformations, syndromic and non-syndromic Cohort 2: Retinitis pigmentosa, achromatopsy, Bardet-Biedl syndrome, Usher syndrome, congenital stationary night blindness, LCA, macula degeneration, rod/ cone dystrophies, opticus atrophy Cohort 3: Rare paediatric solid cancers as melanoma, carcinoma of the gastrointestinal tract, tumours of the salivary gland and pancreatic tumors in children.
Who cannot join
- Cohort 1: Toxic causes (drugs, infections) Cohort 2: patients with non-genetic forms of blindness Cohort 3: adult cancer, blood cancer
- Missing informed consent of the patient/ legal guardian
- Missing samples of both parents
- Previous WES or panel analysis-
Trial locations and contacts
1 site in 1 country.
About this study
The GENOME FIRST APPROACH project will enroll patients (n = 450) and their healthy parents with unclear molecular cause of the disease, suspected genetic cause of the disease and the healthy parents of those affected for trio analysis (N in total 1350).
Read the detailed description
In the GENOME FIRST APPROACH (monocentric, prospective, open-label diagnostic) project, patients with molecularly undiagnosed diseases will diagnostically be analyzed by Whole Genome Sequencing (WGS)-trio analysis. The following questions will be leading the project:
Primary:
- Efficacy of WGS trio analysis in different clinical indications
Secondary:
- Systematically benchmark WGS analysis to detect genetic variations compared to WES and single nucleotide polymorphism (SNP) array analysis,
- Expand the analysis from coding single-nucleotide variants (SNVs) to regulatory mutations, structural variants (SVs), and low complexity regions,
- Validate the efficacy of clinical genome trio sequencing in a routine diagnostic setting,
- Analyse whether 42x coverage has the potential to discover mosaicism as disease causing mechanism,
- Further develop algorithms for integrative analyses of Trio-WGS data with Ribonucleic acid- sequencing (RNA-seq),
- Identify de novo alterations and novel disease mechanisms,
- Gain fundamental new insights into disease mechanisms and cellular biology,
- Combine WGS with further Omics methods to improve genetic diagnostics of future rare disease patients, and
- Explore overall financial costs and time to report conclusive data to the patients of the Trio-WGS approach compared to traditional multistep diagnostic approaches using single-gene, panel, whole-exome sequencing (WES) and chromosomal microarray (CMA) (SNP array, array-based comparative genomic hybridization (arrayCGH)) analysis.
In addition, healthy parents of the subjects will be included in the project to perform parent-child (trio) analyzes.
- Conditions
- Rare Diseases, Genetic Predisposition
- Being tested
- WGS-Diagnostic
- Keywords
- Rare Diseases, Genetic Predisposition, Whole-exome sequencing, WGS-trio analysis, Whole Genome Sequencing (WGS)
- Medical subject headings
- Rare Diseases, Genetic Predisposition to Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
WGS-DiagnosticGenetic
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-seq.
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1: Intellectual disability | Other | Genetic: WGS Diagnostic Blood take for genetic diagnostic. Receives: Genetic: WGS-Diagnostic |
| Cohort 2 Retinal diseases | Other | Genetic: WGS Diagnostic Blood take for genetic diagnostic. Receives: Genetic: WGS-Diagnostic |
| Cohort 3: Rare tumors in childhood | Other | Genetic: WGS Diagnostic Blood take for genetic diagnostic. Receives: Genetic: WGS-Diagnostic |
What is being measured
The primary outcome is the main question the study is designed to answer.
Full genomic sequence analysis carried out by Whole Genome Sequencing (WGS)
Number of genomic variants in disease and health parents by WGS (a Next-Generation Sequencing Technology, NGS)
Measured: Day 1
Secondary outcomes (2)
Genome sequencing
Verification of the genetic causes of unclear genetic diseases by clinical genome sequencing
Measured: Day 1
De novo alterations
Number of de novo alterations in genome of the enrolled population
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 posted17 May 2019
- Study start1 Oct 2019
- Primary completion1 Oct 2022
- Study completion1 Oct 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Rare DiseasesStudies of the same condition, open and under way.
- More trials run by University Hospital TuebingenThe sponsor's other registered studies.
- 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
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- Cohort 1: IQ \< 70 with and without malformations, syndromic and non-syndromic Cohort 2: Retinitis pigmentosa, achromatopsy, Bardet-Biedl syndrome, Usher syndrome, congenital stationary night blindness, LCA, macula degeneration, rod/ cone dystrophies, opticus atrophy Cohort 3: Rare paediatric solid cancers as melanoma, carcinoma of the gastrointestinal tract, tumours of the salivary gland and pancreatic tumors in children. Plus: their respective parents
- Masking
- None (open label)
- Enrolment
- 1,350 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital Tuebingen
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Olaf Riess, Prof. Dr., Study director, University Hospital Tuebingen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03954652
- Sponsor's protocol ID
- WG-Trio01
- Status last verified
- Oct 2022
- First submitted
- 9 May 2019
- Last updated
- 18 Oct 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Oct 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Whole Genome Trio Sequencing as a Standard Routine Test in Patients With Rare Diseases - "GENOME FIRST APPROACH"
- ClinicalTrials.gov ID
- NCT03954652
- Acronym / sponsor ID
- WG-Trio01
- Conditions
- Rare Diseases, Genetic Predisposition
- Keywords
- Rare Diseases, Genetic Predisposition, Whole-exome sequencing, WGS-trio analysis, Whole Genome Sequencing (WGS)
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 1,350 participants (actual)
- Lead sponsor
- University Hospital TuebingenUniversity, hospital or other
- Study start
- 1 Oct 2019 (actual)
- Primary completion
- 1 Oct 2022 (actual)
- Study completion
- 1 Oct 2022 (actual)
- First posted
- 17 May 2019 (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 GENOME FIRST APPROACH project will enroll patients (n = 450) and their healthy parents with unclear molecular cause of the disease, suspected genetic cause of the disease and the healthy parents of those affected for trio analysis (N in total 1350).
Detailed description
In the GENOME FIRST APPROACH (monocentric, prospective, open-label diagnostic) project, patients with molecularly undiagnosed diseases will diagnostically be analyzed by Whole Genome Sequencing (WGS)-trio analysis. The following questions will be leading the project:
Primary:
- Efficacy of WGS trio analysis in different clinical indications
Secondary:
- Systematically benchmark WGS analysis to detect genetic variations compared to WES and single nucleotide polymorphism (SNP) array analysis,
- Expand the analysis from coding single-nucleotide variants (SNVs) to regulatory mutations, structural variants (SVs), and low complexity regions,
- Validate the efficacy of clinical genome trio sequencing in a routine diagnostic setting,
- Analyse whether 42x coverage has the potential to discover mosaicism as disease causing mechanism,
- Further develop algorithms for integrative analyses of Trio-WGS data with Ribonucleic acid- sequencing (RNA-seq),
- Identify de novo alterations and novel disease mechanisms,
- Gain fundamental new insights into disease mechanisms and cellular biology,
- Combine WGS with further Omics methods to improve genetic diagnostics of future rare disease patients, and
- Explore overall financial costs and time to report conclusive data to the patients of the Trio-WGS approach compared to traditional multistep diagnostic approaches using single-gene, panel, whole-exome sequencing (WES) and chromosomal microarray (CMA) (SNP array, array-based comparative genomic hybridization (arrayCGH)) analysis.
In addition, healthy parents of the subjects will be included in the project to perform parent-child (trio) analyzes.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
- Model description
- Cohort 1: IQ < 70 with and without malformations, syndromic and non-syndromic Cohort 2: Retinitis pigmentosa, achromatopsy, Bardet-Biedl syndrome, Usher syndrome, congenital stationary night blindness, LCA, macula degeneration, rod/ cone dystrophies, opticus atrophy Cohort 3: Rare paediatric solid cancers as melanoma, carcinoma of the gastrointestinal tract, tumours of the salivary gland and pancreatic tumors in children. Plus: their respective parents
| Arm | Type | Receives |
|---|---|---|
| Cohort 1: Intellectual disability | Other | Genetic: WGS-DiagnosticGenetic: WGS Diagnostic Blood take for genetic diagnostic. |
| Cohort 2 Retinal diseases | Other | Genetic: WGS-DiagnosticGenetic: WGS Diagnostic Blood take for genetic diagnostic. |
| Cohort 3: Rare tumors in childhood | Other | Genetic: WGS-DiagnosticGenetic: WGS Diagnostic Blood take for genetic diagnostic. |
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
- Suspected genetic cause of the disease
- Healthy parents of those affected for trio analysis Cohort 1: IQ < 70 with and without malformations, syndromic and non-syndromic Cohort 2: Retinitis pigmentosa, achromatopsy, Bardet-Biedl syndrome, Usher syndrome, congenital stationary night blindness, LCA, macula degeneration, rod/ cone dystrophies, opticus atrophy Cohort 3: Rare paediatric solid cancers as melanoma, carcinoma of the gastrointestinal tract, tumours of the salivary gland and pancreatic tumors in children.
Key exclusion criteria (4 listed)
- Cohort 1: Toxic causes (drugs, infections) Cohort 2: patients with non-genetic forms of blindness Cohort 3: adult cancer, blood cancer
- Missing informed consent of the patient/ legal guardian
- Missing samples of both parents
- Previous WES or panel analysis-
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 |
|---|---|---|
| WGS-DiagnosticBlood 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-seq. | Genetic | Cohort 1: Intellectual disability, Cohort 2 Retinal diseases, Cohort 3: Rare tumors in childhood |
Primary outcome
Full genomic sequence analysis carried out by Whole Genome Sequencing (WGS)
Time frame: Day 1
Number of genomic variants in disease and health parents by WGS (a Next-Generation Sequencing Technology, NGS)
2 secondary outcomes
Genome sequencing
Time frame: Day 1
De novo alterations
Time frame: Day 1
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Oct 2022.
- Individual participant dataSharing planned: No
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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. This study is not recruiting at the moment.
Olaf Riess, Prof. Dr. study director
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 WGS-Diagnostic in people with Rare Diseases and 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 4 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: finished, as of the sponsor's last update on 18 Oct 2022. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Full genomic sequence analysis carried out by Whole Genome Sequencing (WGS) (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 18 Oct 2022.