Hereditary Hemorrhagic TelangiectasiaCARDI-HHTNCT07101575
Cardiac Evaluation in Hereditary Hemorrhagic Telangiectasia
An observational study of Hereditary Hemorrhagic Telangiectasia, run by Fondazione Policlinico Universitario Agostino Gemelli IRCCS.
Trial summary
Hereditary haemorrhagic telangiectasia (HHT) is a rare autosomal dominant genetic disease associated with mutations in genes encoding proteins of the transforming growth factor β (TGF-β) family, i.e. endoglin (ENG), activin receptor A (ACVRL1), and SMAD 4 (small mother against decapentaplegic 4). Read more about this study
- Who is it for?
- Ages 10 to 80 years
- Conditions the study is for
- Hereditary Hemorrhagic Telangiectasia
- What is being tested?
- Transthoracic echocardiography
- Type of treatment
- Injection or infusion
- How many people
- 380 participants
- Where
- No sites listed yet
- Study dates
- 5 Aug 2025to 31 Dec 2030
- 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 10 to 80 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: 380 patients will be enrolled, approximately 30 of whom are between the ages of 10 and 18. These patients currently undergo echocardiography with bubble test for pulmonary arteriovenous malformation (AVM) screening, as part of the hereditary haemorrhagic telangiectasia (HHT) clinical care pathway and therefore as part of standard clinical practice. Pregnant women and paediatric patients (aged 10 and older) will constitute subgroups and will be analysed separately.
Who may be able to join
- Patients > 10 years of age with a genetic diagnosis, i.e. a pathogenic mutation in the endoglin (ENG), activin receptor A (ACVRL1) or small mother against decapentaplegic (SMAD4) gene, and/or a clinically confirmed diagnosis of hereditary hemorrhagic teleangectasia (HHT) according to the Curaçao criteria
- Signed informed consent
Who cannot join
- Patients whose echocardiographic images are of suboptimal quality and cannot be adequately analysed.
- No signed informed consent
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
Official title: Cardiac Observational Study of Patients With Hereditary Hemorrhagic Telangiectasia
Hereditary haemorrhagic telangiectasia (HHT) is a rare autosomal dominant genetic disease associated with mutations in genes encoding proteins of the transforming growth factor β (TGF-β) family, i.e. endoglin (ENG), activin receptor A (ACVRL1), and SMAD 4 (small mother against decapentaplegic 4). Mutations in any of these genes lead to the onset of arteriovenous malformations (AVMs). The clinical consequences of this syndrome are primarily AVM-associated complications.
Major cardiovascular consequences occur in the more advanced stages, but their prevalence is low. Most HHT patients are asymptomatic, and ischemic heart disease has a significantly lower prevalence than in the general population. The limited sample size of studies currently published in the literature makes it difficult to characterize any subclinical cardiovascular alterations in asymptomatic HHT subjects.
Read more
Alterations in TGF-β family proteins likely result in a protective effect on the coronary circulation against atherosclerosis. A thorough understanding of the potential protective factors against coronary artery disease, underlying HHT alterations, may allow the development of gene therapy models inspired by the HHT phenotype. Some manifestations of extracellular matrix remodelling at the tissue level (i.e. myocardial and valvular) may be more prevalent in HHT patients than in the general population. Finally, any subclinical alterations in cardiac function related to chronic anaemia and possible iron overload due to iron replacement therapy are not yet known.
Primary objective of the study will be to perform a complete echocardiographic characterization, using new imaging methods aimed at identifying even subclinical dysfunctions of cardiac mechanics, including a phenotyping of the morphology and function of the valvular systems, as well as paradoxical shunts.
Secondary objectives of the study will be: 1) To verify whether there are echocardiographic differences, related to extracellular matrix remodelling, in addition to the presence of shunts, between the various HHT genotypes and to identify any genotype-phenotype correlations. 2)To verify the impact of chronic anaemia and iron supplementation on cardiac mechanics in relation to possible genotype-phenotype interactions.
About study methodology, collection and analysis of clinical and echocardiographic data will be obtained from routine cardiac assessments performed as part of the HHT clinical-care pathway.
- Conditions
- Hereditary Hemorrhagic Telangiectasia
- Being tested
- Transthoracic echocardiography
- Medical subject headings
- Telangiectasia, Hereditary Hemorrhagic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Transthoracic echocardiographyDiagnostic test
Transthoracic echocardiography with bubble test, by intravenous infusion of agitate saline solution
What is being measured
The primary outcome is the main question the study is designed to answer.
Evaluation of suclinical cardiac mechanical dysfunction
Perform a comprehensive echocardiographic characterization, using new imaging techniques to identify even subclinical cardiac mechanical dysfunction, including phenotyping of the morphology and function of the valvular systems, as well as paradoxical shunts
Measured: 30 minutes
Secondary outcomes (2)
Genotype-phenotype correlations
Verify whether there are echocardiographic differences related to extracellular matrix remodelling, in addition to the presence of shunts, between the various hereditary hemorrhagic telangiectasia (HHT) genotypes and identify any genotype-phenotype correlations
Measured: 6 months
Impact of chronic anaemia
Verify the impact of chronic anaemia and iron supplementation on cardiac mechanics in relation to possible genotype-phenotype interactions
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Aug 2025
- Study start5 Aug 2025 (estimated)
- Primary completion5 Aug 2030 (estimated)
- Study completion31 Dec 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hereditary Hemorrhagic TelangiectasiaStudies 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
- 380 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Fondazione Policlinico Universitario Agostino Gemelli IRCCS
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Gabriella Locorotondo, Principal investigator, Fondazione Policlinico Universitario A.Gemelli IRCCS Roma
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07101575
- Sponsor's protocol ID
- 7459
- Acronym
- CARDI-HHT
- Status last verified
- Jul 2025
- First submitted
- 28 Jul 2025
- Last updated
- 14 Aug 2025
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 Aug 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Cardiac Observational Study of Patients With Hereditary Hemorrhagic Telangiectasia
- ClinicalTrials.gov ID
- NCT07101575
- Acronym / sponsor ID
- CARDI-HHT / 7459
- Conditions
- Hereditary Hemorrhagic Telangiectasia
- Study type
- Observational
- Recruitment status
- Not yet recruiting
- Enrolment
- 380 participants (estimated)
- Lead sponsor
- Fondazione Policlinico Universitario Agostino Gemelli IRCCSUniversity, hospital or other
- Study start
- 5 Aug 2025 (estimated)
- Primary completion
- 5 Aug 2030 (estimated)
- Study completion
- 31 Dec 2030 (estimated)
- First posted
- 3 Aug 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.
Hereditary haemorrhagic telangiectasia (HHT) is a rare autosomal dominant genetic disease associated with mutations in genes encoding proteins of the transforming growth factor β (TGF-β) family, i.e. endoglin (ENG), activin receptor A (ACVRL1), and SMAD 4 (small mother against decapentaplegic 4). Mutations in any of these genes lead to the onset of arteriovenous malformations (AVMs). The clinical consequences of this syndrome are primarily AVM-associated complications.
Major cardiovascular consequences occur in the more advanced stages, but their prevalence is low. Most HHT patients are asymptomatic, and ischemic heart disease has a significantly lower prevalence than in the general population. The limited sample size of studies currently published in the literature makes it difficult to characterize any subclinical cardiovascular alterations in asymptomatic HHT subjects.
Alterations in TGF-β family proteins likely result in a protective effect on the coronary circulation against atherosclerosis. A thorough understanding of the potential protective factors against coronary artery disease, underlying HHT alterations, may allow the development of gene therapy models inspired by the HHT phenotype. Some manifestations of extracellular matrix remodelling at the tissue level (i.e. myocardial and valvular) may be more prevalent in HHT patients than in the general population. Finally, any subclinical alterations in cardiac function related to chronic anaemia and possible iron overload due to iron replacement therapy are not yet known.
Primary objective of the study will be to perform a complete echocardiographic characterization, using new imaging methods aimed at identifying even subclinical dysfunctions of cardiac mechanics, including a phenotyping of the morphology and function of the valvular systems, as well as paradoxical shunts.
Secondary objectives of the study will be: 1) To verify whether there are echocardiographic differences, related to extracellular matrix remodelling, in addition to the presence of shunts, between the various HHT genotypes and to identify any genotype-phenotype correlations. 2)To verify the impact of chronic anaemia and iron supplementation on cardiac mechanics in relation to possible genotype-phenotype interactions.
About study methodology, collection and analysis of clinical and echocardiographic data will be obtained from routine cardiac assessments performed as part of the HHT clinical-care pathway.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 10 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- 380 patients will be enrolled, approximately 30 of whom are between the ages of 10 and 18. These patients currently undergo echocardiography with bubble test for pulmonary arteriovenous malformation (AVM) screening, as part of the hereditary haemorrhagic telangiectasia (HHT) clinical care pathway and therefore as part of standard clinical practice. Pregnant women and paediatric patients (aged 10 and older) will constitute subgroups and will be analysed separately.
Key inclusion criteria (2 listed)
- Patients > 10 years of age with a genetic diagnosis, i.e. a pathogenic mutation in the endoglin (ENG), activin receptor A (ACVRL1) or small mother against decapentaplegic (SMAD4) gene, and/or a clinically confirmed diagnosis of hereditary hemorrhagic teleangectasia (HHT) according to the Curaçao criteria
- Signed informed consent
Key exclusion criteria (2 listed)
- Patients whose echocardiographic images are of suboptimal quality and cannot be adequately analysed.
- No signed informed consent
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 |
|---|---|---|
| Transthoracic echocardiographyTransthoracic echocardiography with bubble test, by intravenous infusion of agitate saline solution | Diagnostic test | – |
Primary outcome
Evaluation of suclinical cardiac mechanical dysfunction
Time frame: 30 minutes
Perform a comprehensive echocardiographic characterization, using new imaging techniques to identify even subclinical cardiac mechanical dysfunction, including phenotyping of the morphology and function of the valvular systems, as well as paradoxical shunts
2 secondary outcomes
Genotype-phenotype correlations
Time frame: 6 months
Impact of chronic anaemia
Time frame: 6 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 14 Aug 2025.
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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.
Gabriella Locorotondo principal investigator
Fondazione Policlinico Universitario A.Gemelli IRCCS Roma
Questions about this trial
What is this clinical trial studying?
An observational study of Hereditary Hemorrhagic Telangiectasia, run by Fondazione Policlinico Universitario Agostino Gemelli IRCCS.
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 2 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 14 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.
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 Gabriella Locorotondo (+39 0630154187, gabriella.locorotondo@policlinicogemelli.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Evaluation of suclinical cardiac mechanical dysfunction (time frame: 30 minutes). 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 14 Aug 2025.