Heart TransplantationNCT06012162
Genomics in Heart Transplants
An observational study of Heart Transplantation, run by Heinrich-Heine University, Duesseldorf at 1 site in Germany.
Trial summary
A cross-sectional analysis of 200 heart transplant recipients, combining in-depth phenotyping and risk factor assessment (cardiac MRI, coronary angiogram with OCT, cardiorespiratory exercise tests, exogenic factors like nutrition, smoking, lipid profile) with short-read whole-genome sequencing to elucidate the… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Heart Transplantation
- How many people
- 200 participants
- Where
- 1 siteGermany
- Study dates
- Jan 2024to Jan 2028
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Patients undergoing heart transplantation
Who may be able to join
- Patients > 18 years old undergoing heart transplantation in our centre
Who cannot join
- < 18 years
- incapable of giving consent
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 Düsseldorf Division of Cardiology, Pulmonary Disease and Vascular Medicine
Düsseldorf, 40225
Clinical Trial Unit, +492118105315, ctu@med.uni-duesseldorf.de
Daniel Oehler, MD
About this study
Official title: Long-read Genome Sequencing and Risk Stratification of Myocardial Ischemia in Patients With Heart Transplantation
A cross-sectional analysis of 200 heart transplant recipients, combining in-depth phenotyping and risk factor assessment (cardiac MRI, coronary angiogram with OCT, cardiorespiratory exercise tests, exogenic factors like nutrition, smoking, lipid profile) with short-read whole-genome sequencing to elucidate the interplay of established PRS from the literature and exogenic risk factors with respect to HTx outcomes will be carried out.
Besides that, a long-read whole-genome sequencing of 100 newly transplanted recipients and their corresponding donors and extend latest bioinformatics methods developed by the study to analyze long-read data will be performed. This will enable a comprehensive and integrated analysis of structural variants, polygenic risk, high-penetrance variant genotypes, immunogenetic (major and minor histocompatibility), and individual lifestyle risk factors in a unique donor-recipient cohort, elucidating the extent of within-cohort variability and cross-correlations between the considered potential risk factors and an exploratory analysis of the utility of genetic risk scores in light of the study results will be carried out.
Read the detailed description
Background: Heart transplantation (HTx) is the treatment of choice for patients with end-stage heart failure who remain symptomatic despite optimal medical therapy. Even with best-practice follow-up care, one out of eight HTx patients eventually die of ischemic cardiomyopathy and recurrent acute myocardial infarction (AMI). Classical risk factors like the recipient indication for heart transplantation explain a fraction of adverse outcomes, but no conventional risk factor alone satisfactorily predicts the probability of cardiac allograft vasculopathy (CAV) or recurrent AMI in HTx patients; in addition, the underlying pathomechanisms are poorly understood.
Therefore, there is an urgent need for an improved understanding of the factors contributing to recurrent myocardial ischemia in HTx patients. Recent large-scale studies of the genetic architecture of coronary artery disease in the general population indicate that polygenic risk scores (PRS) explain more disease risk than any single non-genetic risk factor, but, due to a lack of longitudinal follow-up studies with deep phenotyping, PRS have not yet been widely adopted in clinical practice. Furthermore, current genetic studies are based on microarrays or short-read sequencing, severely limiting their ability to characterize the effect of complex or structural genetic variation, in the whole human genome as well as in key loci of potential importance for HTx outcomes, affecting, e.g., lipid metabolism (e.g. LPA) and immunogenetic compatibility (e.g. the major histocompatibility complex).
In summary, there is presently no study leveraging the improved ability to resolve human genomes with long-read sequencing technologies in a deeply phenotyped cohort for an improved understanding of recurring myocardial ischemia.
Study design and aims: In an innovative three-component study design, comprehensive phenotyping with the latest long-read sequencing technology and algorithmic advances in computational genomics to elucidate the interplay of genetic and non-genetic risk factors of myocardial ischemia in HTx patients at unprecedented resolution and pave the way towards detailed risk stratification and tailored treatment, will be combined
Significance and translational potential: By enabling the integrated analysis of structural variants, high-penetrance complex variants, and high-resolution immunogenetics, long-read sequencing will enable improved genetic models of the development of ischemia in HTx patients and contribute to an improved understanding of underlying pathomechanisms. Based on this, the investigators will be able to propose schemes to incorporate integrated risk scores in future clinical trials for personalized treatment stratification.
- Conditions
- Heart Transplantation
- Keywords
- heart transplantation, long-read genomics, risk stratification, myocardial ischemia
- Medical subject headings
- Myocardial Ischemia
What is being measured
The primary outcome is the main question the study is designed to answer.
rate of Clinically significant ischemia
defined by cardiac allograft vasculopathy (CAV) grade >1 \& cardiac magnetic resonance imaging (cMRI)
Measured: 5 years
Secondary outcomes (6)
cardiovascular death
cardiovascular event as primary cause of death
Measured: 5 years
myocardial infarction
Incidence of Type I or II myocardial infarction (assessed by CMR, electrocardiogram, laboratory parameters according to the 4th universal definition of myocardial infarction)
Measured: 5 years
Hospitalisation (w/o allograft rejection)
All-cause hospitalisation with exception of acute allograft rejection
Measured: 5 years
Cardiac allograft vasculopathy (macrocirculatory)
Incidence: Coronary angiogram (+/- optic coherence tomography (OCT))
Measured: 5 years
number of coronary microvascular dysfunction
measured by fractional flow reserve
Measured: 5 years
number of coronary microvascular dysfunction
measured by cardiac magnetic resonance imaging
Measured: 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Aug 2023
- Study startJan 2024 (estimated)
- Primary completionJan 2028 (estimated)
- Study completionJan 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Heart TransplantationStudies 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 200 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Heinrich-Heine University, Duesseldorf
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Malte Kelm, Prof., Study chair, Clinic for Cardiology, Pneumology and Angiology at University Hospital Düsseldorf
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06012162
- Sponsor's protocol ID
- Genomics in HTx
- Status last verified
- Aug 2023
- First submitted
- 4 Apr 2023
- Last updated
- 25 Aug 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Long-read Genome Sequencing and Risk Stratification of Myocardial Ischemia in Patients With Heart Transplantation
- ClinicalTrials.gov ID
- NCT06012162
- Acronym / sponsor ID
- Genomics in HTx
- Conditions
- Heart Transplantation
- Keywords
- heart transplantation, long-read genomics, risk stratification, myocardial ischemia
- Study type
- Observational
- Recruitment status
- Not yet recruiting
- Enrolment
- 200 participants (estimated)
- Lead sponsor
- Heinrich-Heine University, DuesseldorfUniversity, hospital or other
- Study start
- Jan 2024 (estimated)
- Primary completion
- Jan 2028 (estimated)
- Study completion
- Jan 2028 (estimated)
- First posted
- 25 Aug 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.
A cross-sectional analysis of 200 heart transplant recipients, combining in-depth phenotyping and risk factor assessment (cardiac MRI, coronary angiogram with OCT, cardiorespiratory exercise tests, exogenic factors like nutrition, smoking, lipid profile) with short-read whole-genome sequencing to elucidate the interplay of established PRS from the literature and exogenic risk factors with respect to HTx outcomes will be carried out.
Besides that, a long-read whole-genome sequencing of 100 newly transplanted recipients and their corresponding donors and extend latest bioinformatics methods developed by the study to analyze long-read data will be performed. This will enable a comprehensive and integrated analysis of structural variants, polygenic risk, high-penetrance variant genotypes, immunogenetic (major and minor histocompatibility), and individual lifestyle risk factors in a unique donor-recipient cohort, elucidating the extent of within-cohort variability and cross-correlations between the considered potential risk factors and an exploratory analysis of the utility of genetic risk scores in light of the study results will be carried out.
Detailed description
Background: Heart transplantation (HTx) is the treatment of choice for patients with end-stage heart failure who remain symptomatic despite optimal medical therapy. Even with best-practice follow-up care, one out of eight HTx patients eventually die of ischemic cardiomyopathy and recurrent acute myocardial infarction (AMI). Classical risk factors like the recipient indication for heart transplantation explain a fraction of adverse outcomes, but no conventional risk factor alone satisfactorily predicts the probability of cardiac allograft vasculopathy (CAV) or recurrent AMI in HTx patients; in addition, the underlying pathomechanisms are poorly understood.
Therefore, there is an urgent need for an improved understanding of the factors contributing to recurrent myocardial ischemia in HTx patients. Recent large-scale studies of the genetic architecture of coronary artery disease in the general population indicate that polygenic risk scores (PRS) explain more disease risk than any single non-genetic risk factor, but, due to a lack of longitudinal follow-up studies with deep phenotyping, PRS have not yet been widely adopted in clinical practice. Furthermore, current genetic studies are based on microarrays or short-read sequencing, severely limiting their ability to characterize the effect of complex or structural genetic variation, in the whole human genome as well as in key loci of potential importance for HTx outcomes, affecting, e.g., lipid metabolism (e.g. LPA) and immunogenetic compatibility (e.g. the major histocompatibility complex).
In summary, there is presently no study leveraging the improved ability to resolve human genomes with long-read sequencing technologies in a deeply phenotyped cohort for an improved understanding of recurring myocardial ischemia.
Study design and aims: In an innovative three-component study design, comprehensive phenotyping with the latest long-read sequencing technology and algorithmic advances in computational genomics to elucidate the interplay of genetic and non-genetic risk factors of myocardial ischemia in HTx patients at unprecedented resolution and pave the way towards detailed risk stratification and tailored treatment, will be combined
Significance and translational potential: By enabling the integrated analysis of structural variants, high-penetrance complex variants, and high-resolution immunogenetics, long-read sequencing will enable improved genetic models of the development of ischemia in HTx patients and contribute to an improved understanding of underlying pathomechanisms. Based on this, the investigators will be able to propose schemes to incorporate integrated risk scores in future clinical trials for personalized treatment stratification.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients undergoing heart transplantation
Key inclusion criteria (1 listed)
- Patients > 18 years old undergoing heart transplantation in our centre
Key exclusion criteria (2 listed)
- < 18 years
- incapable of giving consent
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
rate of Clinically significant ischemia
Time frame: 5 years
defined by cardiac allograft vasculopathy (CAV) grade >1 \& cardiac magnetic resonance imaging (cMRI)
6 secondary outcomes
cardiovascular death
Time frame: 5 years
myocardial infarction
Time frame: 5 years
Hospitalisation (w/o allograft rejection)
Time frame: 5 years
Cardiac allograft vasculopathy (macrocirculatory)
Time frame: 5 years
number of coronary microvascular dysfunction
Time frame: 5 years
number of coronary microvascular dysfunction
Time frame: 5 years
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 25 Aug 2023.
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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.
Malte Kelm, Prof. study chair
Clinic for Cardiology, Pneumology and Angiology at University Hospital Düsseldorf
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Heart Transplantation, run by Heinrich-Heine University, Duesseldorf 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 1 inclusion and 2 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 25 Aug 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 Daniel Oehler, MD (+492118118800, Daniel.oehler@med.uni-duesseldorf.de), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
rate of Clinically significant ischemia (time frame: 5 years). 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 25 Aug 2023.