Long QT SyndromeCarDiagNCT06087367
Building of a Diagnostic/Prognostic Database for Human ERG Variant Effects
An observational study of Long QT Syndrome, run by Nantes University Hospital at 2 sites in France.
Trial summary
Cardiac channelopathies induce severe heart rhythm or conduction disorders. Mutations of the KCNH2 gene, that encodes the human (h) ERG channel, is responsible for 30-40% of all cases of long QT syndrome (inherited LQT2). Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Long QT Syndrome
- How many people
- 600 participants
- Where
- 2 sitesFrance
- Study dates
- 20 Sep 2021to 24 Mar 2026
- Phase
- Observational
- 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
Study population: A collective effort will be conducted by all partners on identifying sets of priorities for KCNH2 variants. Priority 1 will be all the variants for which clinical and genetic data cannot decide on their own about the pathogenicity. All French variants will be included in this group. It may be enlarged by interesting variants identified from Clinvar. Priority 2 variants will be those for which pathogenicity is established but for which additional functional, pharmacological and structural data may be of interest. Special mention will be attributed to the variants that localize on hERG regions well defined structurally. Priority 3 are all other variants.
Who may be able to join
- Patients carrier of a mutation in KCNH2 gene
Who cannot join
- Patients who refuse to take part to research
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
France2 sites, 2 recruiting
- Recruiting
Nantes university hospital
Nantes, Loire-atlantique, 44093
Vincent Probst, PUPH, +33240165279, vincent.probst@chu-nantes.fr
- Recruiting
Hôpital Bichat - Claude Bernard
Paris, 75018
Isabelle Denjoy, Dr
About this study
Official title: Building of a Diagnostic/Prognostic Database by High-throughput Multiplexed Assays for Human ERG Variant Effects
Cardiac channelopathies induce severe heart rhythm or conduction disorders. Mutations of the KCNH2 gene, that encodes the human (h) ERG channel, is responsible for 30-40% of all cases of long QT syndrome (inherited LQT2). Besides, hERG is frequently responsible for off-target effects of several pharmacological agents (acquired LQT2). With the advent of Next Generation Sequencing, hundreds of new KCNH2 variants are accumulating in regional databases including those developed by french centers of references. Worldwide, we estimate there are more than 1000 variants for hERG channel. Unfortunately, many of these new variants appear to be of unknown functional significance in spite of available clinical and genetic information. Little is known on whether they affect the channel biophysical properties, its expression at the cell surface and/or its structure. Yet, this information is crucial to determine the real degree of pathogenicity of these variants, and therefore to make the proper diagnosis on inherited LQT2, counsel the patient for his treatment and improve the management of the patient's life. Our ambition is therefore to tackle this issue of variant significance by (i) launching a large-scale multi-functional evaluation of hERG variants, (ii) introducing for the first time a formatted large-scale pathogenicity annotation score for all variants that have been functionally evaluated by this multi-parametric approach, and (iii) regrouping all the relevant information collected in every French Regional centers of reference into a single National database hosted by an infrastructure that possesses enough flexibility for continuous data implementation and cross-referencing. The database will integrate the latest International guidelines for functional pathogenicity annotation. This project will also include the pharmacological characterization of several drugs susceptible to produce acquired LQT2 with variable severities. We aim to understand whether there are structural regions within hERG channel in which the introduction of a variant is more prone to increase the risk of acquired LQT2 or if, on the contrary, a set of variants may relatively protect some patients against LQT2-inducing drugs.
- Conditions
- Long QT Syndrome
- Keywords
- Long QT syndrome, KCNH2 gene variants
- Medical subject headings
- Long QT Syndrome
What is being measured
The primary outcome is the main question the study is designed to answer.
To develop a database listing KCNH2 variants and their clinical impact
Biophysical and pharmacological characterization; Trafficking impact of hERG variants; Structural impact of hERG variants using modeling tools
Measured: 42 months
Secondary outcomes (1)
To stratify KCNH2 gene variants according to their sensitivity to drugs
Stratify KCNH2 gene variants according to their sensitivity to drugs known to induce acquired type 2 long QT syndrome
Measured: 42 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Oct 2023
- Study start20 Sep 2021
- Primary completion31 Dec 2023
- Study completion24 Mar 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Long QT SyndromeStudies of the same condition, open and under way.
- More trials run by Nantes University HospitalThe 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
- Observational
- Observational model
- Case only
- Time perspective
- Retrospective
- Enrolment
- 600 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Nantes University Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Institut National de la Santé Et de la Recherche Médicale, France, Centre National de la Recherche Scientifique, France
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06087367
- Sponsor's protocol ID
- RC21_0456
- Acronym
- CarDiag
- Status last verified
- May 2025
- First submitted
- 12 Oct 2023
- Last updated
- 23 May 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Implementation of a new web-accessible variant-centric database
Study at a glance
From the registry record, last updated by the sponsor on 23 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Building of a Diagnostic/Prognostic Database by High-throughput Multiplexed Assays for Human ERG Variant Effects
- ClinicalTrials.gov ID
- NCT06087367
- Acronym / sponsor ID
- CarDiag / RC21_0456
- Conditions
- Long QT Syndrome
- Keywords
- Long QT syndrome, KCNH2 gene variants
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 600 participants (estimated)
- Lead sponsor
- Nantes University HospitalUniversity, hospital or other
- Collaborators
- Institut National de la Santé Et de la Recherche Médicale, France, Centre National de la Recherche Scientifique, France
- Study start
- 20 Sep 2021 (actual)
- Primary completion
- 31 Dec 2023 (actual)
- Study completion
- 24 Mar 2026 (estimated)
- First posted
- 17 Oct 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.
Cardiac channelopathies induce severe heart rhythm or conduction disorders. Mutations of the KCNH2 gene, that encodes the human (h) ERG channel, is responsible for 30-40% of all cases of long QT syndrome (inherited LQT2). Besides, hERG is frequently responsible for off-target effects of several pharmacological agents (acquired LQT2). With the advent of Next Generation Sequencing, hundreds of new KCNH2 variants are accumulating in regional databases including those developed by french centers of references. Worldwide, we estimate there are more than 1000 variants for hERG channel. Unfortunately, many of these new variants appear to be of unknown functional significance in spite of available clinical and genetic information. Little is known on whether they affect the channel biophysical properties, its expression at the cell surface and/or its structure. Yet, this information is crucial to determine the real degree of pathogenicity of these variants, and therefore to make the proper diagnosis on inherited LQT2, counsel the patient for his treatment and improve the management of the patient's life. Our ambition is therefore to tackle this issue of variant significance by (i) launching a large-scale multi-functional evaluation of hERG variants, (ii) introducing for the first time a formatted large-scale pathogenicity annotation score for all variants that have been functionally evaluated by this multi-parametric approach, and (iii) regrouping all the relevant information collected in every French Regional centers of reference into a single National database hosted by an infrastructure that possesses enough flexibility for continuous data implementation and cross-referencing. The database will integrate the latest International guidelines for functional pathogenicity annotation. This project will also include the pharmacological characterization of several drugs susceptible to produce acquired LQT2 with variable severities. We aim to understand whether there are structural regions within hERG channel in which the introduction of a variant is more prone to increase the risk of acquired LQT2 or if, on the contrary, a set of variants may relatively protect some patients against LQT2-inducing drugs.
Study design
- Observational model
- Case only
- Time perspective
- Retrospective
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- A collective effort will be conducted by all partners on identifying sets of priorities for KCNH2 variants. Priority 1 will be all the variants for which clinical and genetic data cannot decide on their own about the pathogenicity. All French variants will be included in this group. It may be enlarged by interesting variants identified from Clinvar. Priority 2 variants will be those for which pathogenicity is established but for which additional functional, pharmacological and structural data may be of interest. Special mention will be attributed to the variants that localize on hERG regions well defined structurally. Priority 3 are all other variants.
Key inclusion criteria (1 listed)
- Patients carrier of a mutation in KCNH2 gene
Key exclusion criteria (1 listed)
- Patients who refuse to take part to research
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
To develop a database listing KCNH2 variants and their clinical impact
Time frame: 42 months
Biophysical and pharmacological characterization; Trafficking impact of hERG variants; Structural impact of hERG variants using modeling tools
1 secondary outcome
To stratify KCNH2 gene variants according to their sensitivity to drugs
Time frame: 42 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 23 May 2025.
- Individual participant dataSharing planned: Yes. Implementation of a new web-accessible variant-centric database
Related trials for Long QT Syndrome
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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.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Long QT Syndrome, run by Nantes University Hospital at 2 sites in France.
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 1 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: looking for participants now, as of the sponsor's last update on 23 May 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in France. 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 Vincent Probst, PUPH (0240165279, vincent.probst@chu-nantes.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To develop a database listing KCNH2 variants and their clinical impact (time frame: 42 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 23 May 2025.