Variant NucleotideSCHeDULeRSNCT06775613
Solving Challenging Diagnoses Through Ultra-long Read Sequencing
A study testing Long-read sequencing in people with Variant Nucleotide, run by IRCCS Azienda Ospedaliero-Universitaria di Bologna at 1 site in Italy.
Trial summary
If the study is able to demonstrate that the LRS concretely overcomes the technical limitations of diagnostic methods routinely used in laboratories, its clinical application may make possible a more accurate analysis of repeated genomic regions and offer greater sensitivity for identifying SVs (Structural Variants) Read more about this study
- Who is it for?
- Ages 28 days to 65 years
- Conditions the study is for
- Variant Nucleotide
- What is being tested?
- Long-read sequencing
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 1 siteItaly
- Study dates
- 10 Mar 2023to 31 Dec 2025
- 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 28 days to 65 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Patients with pathogenic alterations in the PKD1 gene, aged between 30 and 70 years
- Patients with pathogenic alterations in the CYP21A2 gene or with a not clearly defined genotype, aged between one month and 50 years
- Patients carrying potentially pathogenic CNVs (e.g. new onset and/or in proximity of disease-associated genes), aged between one month up to 70 years
- Availability of a suitable blood sample at the IRCCS Medical Genetics Unit AOUBO
- Acquisition of informed consent.
Who cannot join
- None
Trial locations and contacts
1 site in 1 country.
Italy1 site
IRCCS Azienda Ospedaliero-Universitaria di Bologna
Bologna, Bologna, 40138
About this study
If the study is able to demonstrate that the LRS concretely overcomes the technical limitations of diagnostic methods routinely used in laboratories, its clinical application may make possible a more accurate analysis of repeated genomic regions and offer greater sensitivity for identifying SVs (Structural Variants)
Read the detailed description
The diagnostic performance of LRS, by applying Oxford Nanopore Technology (ONT), will be evaluated through a real-time targeted approach and generation of ultra-long reads, to the identification of pathogenetic variants in genetic disorders with a currently challenging diagnosis due to the presence of pseudogenes (1) and to the precise mapping of SV breakpoints identified by aCGH for the definition of their clinical significance (2).
- Patients with an established molecular diagnosis will be collected for each of the following disorders: 10 with autosomal dominant polycystic kidney disease (ADPKD) and 10 with CYP21 deficiency. Cases with ambiguous results to test possible ONT improvements in terms of time to results and precise molecular characterization will be included. The entire range of mutations affecting each causative gene (PKD1 and CYP21A2, respectively), which globally cover all the possible types of alterations (missense, nonsense, indels, exonic and gene deletions) will be included.
- Collection of other 10 patients carrying copy number variants (CNVs) with aCGH-defined breakpoints mapping close to disease-genes possibly responsible for the observed clinical picture.
The main aim of this proposal is to evaluate ONT efficacy in resolving diagnostic challenges faced in the clinical genomics routine, in situations when a precise molecular diagnosis is often impossible or difficult and extremely time-consuming with current genetic tests. Sanger sequencing, NGS panels and MLPA are routinely used to identify pathogenic variants and CNVs responsible for many monogenic disorders and for the analysis through aCGH patients with isolated or syndromic intellectual disability without a specific clinical suspect. These analyses are long, technically laborious and often not individually conclusive because technical limitations may lead to ambiguous results and prevent definite diagnosis. The intent is to demonstrate that ONT, through a real-time targeted approach to increase coverage in clinically relevant regions during sequencing, outperforms current diagnostic tools in terms of rapidity and sensitivity, considerably improving the efficiency of the diagnostic process. The success of the proposed target ONT approach will provide the proof of principle to implement this strategy for the diagnosis of a wider spectrum of disorders already studied in our laboratory
- Conditions
- Variant Nucleotide
- Being tested
- Long-read sequencing
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Long-read sequencingGenetic
The technology performed belongs to third-generation sequencing strategies and is capable of analysing very long DNA and RNA fragments.
| Study group | Role | What they receive |
|---|---|---|
| Target | Experimental | Sequencing in samples with alterations in the PKD1 or CYP21A2 genes or with deletions identified by aCGH, LRS will be limited to the genes/loci of of interest. Receives: Genetic: Long-read sequencing |
| Genomics | Experimental | The entire genome will be analysed in samples with duplications in order to precisely identify the genomic regions in which the duplicated portions have inserted Receives: Genetic: Long-read sequencing |
What is being measured
The primary outcome is the main question the study is designed to answer.
Genetic anomalies
To determine the sensitivity of the LRS in detectiong genetic variants in hard-to-analyze genomic regions and to enables precise mapping of unbalanced genomic alterations identified by routine diagnostic techniques.
Measured: 24 months
Secondary outcomes (1)
Mapping the breaking points of CNVs
To verify whether the new sequencing technology impacts the analysis and reporting times.
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jan 2025
- Study start10 Mar 2023
- Primary completion20 Mar 2024
- Study completion31 Dec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Variant NucleotideStudies of the same condition, open and under way.
- More trials run by IRCCS Azienda Ospedaliero-Universitaria di BolognaThe 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
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Pamela Magini, Biologist, Principal investigator, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Policlinico di Sant'Orsola
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06775613
- Sponsor's protocol ID
- SCHeDULeRS
- Other IDs
- Horizon 2020
- Acronym
- SCHeDULeRS
- Status last verified
- Jan 2025
- First submitted
- 28 Nov 2024
- Last updated
- 9 Jan 2026
- 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 9 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Solving Challenging Diagnoses Through Ultra-long Read Sequencing
- ClinicalTrials.gov ID
- NCT06775613
- Acronym / sponsor ID
- SCHeDULeRS / SCHeDULeRS
- Conditions
- Variant Nucleotide
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 15 participants (actual)
- Lead sponsor
- IRCCS Azienda Ospedaliero-Universitaria di BolognaUniversity, hospital or other
- Study start
- 10 Mar 2023 (actual)
- Primary completion
- 20 Mar 2024 (actual)
- Study completion
- 31 Dec 2025 (estimated)
- First posted
- 15 Jan 2025 (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.
If the study is able to demonstrate that the LRS concretely overcomes the technical limitations of diagnostic methods routinely used in laboratories, its clinical application may make possible a more accurate analysis of repeated genomic regions and offer greater sensitivity for identifying SVs (Structural Variants)
Detailed description
The diagnostic performance of LRS, by applying Oxford Nanopore Technology (ONT), will be evaluated through a real-time targeted approach and generation of ultra-long reads, to the identification of pathogenetic variants in genetic disorders with a currently challenging diagnosis due to the presence of pseudogenes (1) and to the precise mapping of SV breakpoints identified by aCGH for the definition of their clinical significance (2).
- Patients with an established molecular diagnosis will be collected for each of the following disorders: 10 with autosomal dominant polycystic kidney disease (ADPKD) and 10 with CYP21 deficiency. Cases with ambiguous results to test possible ONT improvements in terms of time to results and precise molecular characterization will be included. The entire range of mutations affecting each causative gene (PKD1 and CYP21A2, respectively), which globally cover all the possible types of alterations (missense, nonsense, indels, exonic and gene deletions) will be included.
- Collection of other 10 patients carrying copy number variants (CNVs) with aCGH-defined breakpoints mapping close to disease-genes possibly responsible for the observed clinical picture.
The main aim of this proposal is to evaluate ONT efficacy in resolving diagnostic challenges faced in the clinical genomics routine, in situations when a precise molecular diagnosis is often impossible or difficult and extremely time-consuming with current genetic tests. Sanger sequencing, NGS panels and MLPA are routinely used to identify pathogenic variants and CNVs responsible for many monogenic disorders and for the analysis through aCGH patients with isolated or syndromic intellectual disability without a specific clinical suspect. These analyses are long, technically laborious and often not individually conclusive because technical limitations may lead to ambiguous results and prevent definite diagnosis. The intent is to demonstrate that ONT, through a real-time targeted approach to increase coverage in clinically relevant regions during sequencing, outperforms current diagnostic tools in terms of rapidity and sensitivity, considerably improving the efficiency of the diagnostic process. The success of the proposed target ONT approach will provide the proof of principle to implement this strategy for the diagnosis of a wider spectrum of disorders already studied in our laboratory
Study design
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Target | Experimental | Genetic: Long-read sequencingSequencing in samples with alterations in the PKD1 or CYP21A2 genes or with deletions identified by aCGH, LRS will be limited to the genes/loci of of interest. |
| Genomics | Experimental | Genetic: Long-read sequencingThe entire genome will be analysed in samples with duplications in order to precisely identify the genomic regions in which the duplicated portions have inserted |
Who may qualify
- Ages
- 28 days to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (5 listed)
- Patients with pathogenic alterations in the PKD1 gene, aged between 30 and 70 years
- Patients with pathogenic alterations in the CYP21A2 gene or with a not clearly defined genotype, aged between one month and 50 years
- Patients carrying potentially pathogenic CNVs (e.g. new onset and/or in proximity of disease-associated genes), aged between one month up to 70 years
- Availability of a suitable blood sample at the IRCCS Medical Genetics Unit AOUBO
- Acquisition of informed consent.
Key exclusion criteria (1 listed)
- None
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 |
|---|---|---|
| Long-read sequencingThe technology performed belongs to third-generation sequencing strategies and is capable of analysing very long DNA and RNA fragments. | Genetic | Genomics, Target |
Primary outcome
Genetic anomalies
Time frame: 24 months
To determine the sensitivity of the LRS in detectiong genetic variants in hard-to-analyze genomic regions and to enables precise mapping of unbalanced genomic alterations identified by routine diagnostic techniques.
1 secondary outcome
Mapping the breaking points of CNVs
Time frame: 24 months
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 9 Jan 2026.
- 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.
Pamela Magini, Biologist principal investigator
IRCCS Azienda Ospedaliero-Universitaria di Bologna, Policlinico di Sant'Orsola
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Long-read sequencing in people with Variant Nucleotide, run by IRCCS Azienda Ospedaliero-Universitaria di Bologna at 1 site in Italy.
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 5 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: under way, not looking for participants, as of the sponsor's last update on 9 Jan 2026. 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 Italy. 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?
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?
Genetic anomalies (time frame: 24 months). 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 9 Jan 2026.