Hereditary Hemorrhagic TelangiectasiaGenerate-HHTNCT05550376
Genotype-phenotype Association in Hereditary Hemorrhagic Telangiectasia
An observational study of Hereditary Hemorrhagic Telangiectasia and HHT, run by Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal at 1 site in Spain.
Trial summary
The present project aims to study the inflammatory and endothelial responses involved in the differences in clinical events related to both genotypes (ENG vs. ACVRL1) in HHT. Accordingly, a cross-sectional study is proposed to evaluate the differences in circulating inflammatory and endothelial biomarkers, including… Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Hereditary Hemorrhagic Telangiectasia, HHT, Rendu Osler Weber Disease
- What is being tested?
- Registry
- How many people
- 85 participants
- Where
- 1 siteSpain
- Study dates
- 30 Apr 2021to 31 Dec 2023
- How long will I take part?
- 12 Months
- Phase
- Observational
- 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 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: A consecutive sample of patients with HHT will be selected from the subjects under follow-up in the Internal Medicine Department of the Hospital Universitario Ramón y Cajal.
Who may be able to join
- Age between 18 and 75 years.
- Confirmed diagnosis of HHT, according to the Curaçao criteria or genetic diagnosis.
- Clinically stable condition at the time of inclusion, defined as score < 7 points on the Epistaxis Severity Score (ESS).
- Having signed the informed consent, after having received all the information concerning the study.
Who cannot join
- Major coronary or cerebrovascular event in the 3 months prior to inclusion.
- Serious intercurrent illnesses, such as acute infections, outbreaks of autoimmune or inflammatory pathology, active cancer, or other pathologies that, at the investigator's discretion, could interfere with the conduct of the study.
- Major surgery during the 2 months prior to inclusion.
- Pharmacological treatment maintained during the 3 months prior to inclusion with NSAIDs, corticosteroids or chemotherapy.
- Toxic habits, including severe smoking, alcohol or drug abuse, which in the opinion of the investigator could interfere with the conduct of the study.
- Pregnancy or puerperium.
- Any other condition that limits compliance with the visits or procedures established in the protocol.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Genotype-phenotype Association Study of ENG and ACVRL1 Genes in the Inflammatory and Endothelial Response in Hereditary Hemorrhagic Telangiectasia (HHT)
The present project aims to study the inflammatory and endothelial responses involved in the differences in clinical events related to both genotypes (ENG vs. ACVRL1) in HHT. Accordingly, a cross-sectional study is proposed to evaluate the differences in circulating inflammatory and endothelial biomarkers, including interleukines, adhesion molecules, chemokines and immune regulatory molecules between both HHT groups.
Read the detailed description
Background and rationale: Hereditary Hemorrhagic Telangiectasia (HHT) is a rare disease characterized by a multisystemic vascular dysplasia with autosomal dominant inheritance, mainly caused by mutations in ENG and ACVRL1 genes. Even though those mutations have been related to different clinical manifestations, the molecular mechanisms involved in each genetic variant have not been clarified. Methods: A cohort study will be carried out to compare the incidence of clinical events after a 12-months follow-up. The ability of these biomarkers to predict the clinical events will be assessed in a multivariate analysis.
- Being tested
- Registry
- Keywords
- Hereditary Hemorrhagic Telangiectasia, HHT, Rendu Osler Weber Disease, Genotype-phenotype association, ENG, ALK-1
- 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.
RegistryOther
Non-interventional registry
| Study group | Role | What they receive |
|---|---|---|
| HHT1 | Mutations in the ENG (endoglin) gene Receives: Other: Registry | |
| HHT2 | Mutations in the ALK-1 (activin receptor-like kinase) gene Receives: Other: Registry |
What is being measured
The primary outcome is the main question the study is designed to answer.
Hemorrhagic clinical events
Presence of significant bleeding of any location, recurrent and/or massive, or performance of therapeutic procedures to control them.
Measured: 12-month follow-up period after inclusion
Secondary outcomes (2)
Other significant clinical events
Significant clinical events other than hemorrhagic episodes (e.g., infections, neoplasms or other severe diseases)
Measured: 12-month follow-up period after inclusion
Changes in quality of life
Significant changes in quality of life as measured by the EuroQol 5-level EQ-5D version (EQ-5D-5L) and the EuroQol visual analogue scale (EQ VAS).
EQ-5D-5L comprises five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems and extreme problems. The index ranges from 1 (best state of health) to 0 (death).
The EQ VAS records the patient's self-rated health on a vertical visual analogue scale, where the endpoints are labelled 'The best health you can imagine' (100 points) and 'The worst health you can imagine' (0 points).
Measured: 12-month follow-up period after inclusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Sep 2022
- Study start30 Apr 2021
- Primary completion31 Dec 2023
- Study completion31 Dec 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- 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
- 85 participants (actual)
- Target duration
- 12 Months
Sponsor and investigators
- Lead sponsor
- Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal
- Sponsor type
- University, hospital or other
- Collaborators
- Sociedad Española De Medicina Interna
- Responsible party
- Sponsor
- Investigators
- José Luis Patier, MD, Principal investigator, Hospital Universitario Ramon y Cajal
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05550376
- Sponsor's protocol ID
- 301/20
- Acronym
- Generate-HHT
- Status last verified
- Mar 2025
- First submitted
- 19 Sep 2022
- Last updated
- 17 Mar 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Viteri-Noel A, Gonzalez-Garcia A, Patier JL, Fabregate M, Bara-Ledesma N, Lopez-Rodriguez M, Gomez Del Olmo V, Manzano L. Hereditary Hemorrhagic Telangiectasia: Genetics, Pathophysiology, Diagnosis, and Management. J Clin Med. 2022 Sep 5;11(17):5245. doi: 10.3390/jcm11175245.
PubMed 36079173Sanchez-Martinez R, Iriarte A, Mora-Lujan JM, Patier JL, Lopez-Wolf D, Ojeda A, Torralba MA, Juyol MC, Gil R, Anon S, Salazar-Mendiguchia J, Riera-Mestre A; RiHHTa Investigators of the Rare Diseases Working Group from the Spanish Society of Internal Medicine. Current HHT genetic overview in Spain and its phenotypic correlation: data from RiHHTa registry. Orphanet J Rare Dis. 2020 Jun 5;15(1):138. doi: 10.1186/s13023-020-01422-8.
PubMed 32503579Albinana V, Gimenez-Gallego G, Garcia-Mato A, Palacios P, Recio-Poveda L, Cuesta AM, Patier JL, Botella LM. Topically Applied Etamsylate: A New Orphan Drug for HHT-Derived Epistaxis (Antiangiogenesis through FGF Pathway Inhibition). TH Open. 2019 Jul 26;3(3):e230-e243. doi: 10.1055/s-0039-1693710. eCollection 2019 Jul.
PubMed 31360828
Study at a glance
From the registry record, last updated by the sponsor on 17 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Genotype-phenotype Association Study of ENG and ACVRL1 Genes in the Inflammatory and Endothelial Response in Hereditary Hemorrhagic Telangiectasia (HHT)
- ClinicalTrials.gov ID
- NCT05550376
- Acronym / sponsor ID
- Generate-HHT / 301/20
- Keywords
- Hereditary Hemorrhagic Telangiectasia, HHT, Rendu Osler Weber Disease, Genotype-phenotype association, ENG, ALK-1
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 85 participants (actual)
- Lead sponsor
- Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y CajalUniversity, hospital or other
- Collaborators
- Sociedad Española De Medicina Interna
- Study start
- 30 Apr 2021 (actual)
- Primary completion
- 31 Dec 2023 (actual)
- Study completion
- 31 Dec 2023 (actual)
- First posted
- 22 Sep 2022 (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 present project aims to study the inflammatory and endothelial responses involved in the differences in clinical events related to both genotypes (ENG vs. ACVRL1) in HHT. Accordingly, a cross-sectional study is proposed to evaluate the differences in circulating inflammatory and endothelial biomarkers, including interleukines, adhesion molecules, chemokines and immune regulatory molecules between both HHT groups.
Detailed description
Background and rationale: Hereditary Hemorrhagic Telangiectasia (HHT) is a rare disease characterized by a multisystemic vascular dysplasia with autosomal dominant inheritance, mainly caused by mutations in ENG and ACVRL1 genes. Even though those mutations have been related to different clinical manifestations, the molecular mechanisms involved in each genetic variant have not been clarified. Methods: A cohort study will be carried out to compare the incidence of clinical events after a 12-months follow-up. The ability of these biomarkers to predict the clinical events will be assessed in a multivariate analysis.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Target follow-up
- 12 Months
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| HHT1 | – | Other: RegistryMutations in the ENG (endoglin) gene |
| HHT2 | – | Other: RegistryMutations in the ALK-1 (activin receptor-like kinase) gene |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- A consecutive sample of patients with HHT will be selected from the subjects under follow-up in the Internal Medicine Department of the Hospital Universitario Ramón y Cajal.
Key inclusion criteria (4 listed)
- Age between 18 and 75 years.
- Confirmed diagnosis of HHT, according to the Curaçao criteria or genetic diagnosis.
- Clinically stable condition at the time of inclusion, defined as score < 7 points on the Epistaxis Severity Score (ESS).
- Having signed the informed consent, after having received all the information concerning the study.
Key exclusion criteria (7 listed)
- Major coronary or cerebrovascular event in the 3 months prior to inclusion.
- Serious intercurrent illnesses, such as acute infections, outbreaks of autoimmune or inflammatory pathology, active cancer, or other pathologies that, at the investigator's discretion, could interfere with the conduct of the study.
- Major surgery during the 2 months prior to inclusion.
- Pharmacological treatment maintained during the 3 months prior to inclusion with NSAIDs, corticosteroids or chemotherapy.
- Toxic habits, including severe smoking, alcohol or drug abuse, which in the opinion of the investigator could interfere with the conduct of the study.
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 |
|---|---|---|
| RegistryNon-interventional registry | Other | HHT1, HHT2 |
Primary outcome
Hemorrhagic clinical events
Time frame: 12-month follow-up period after inclusion
Presence of significant bleeding of any location, recurrent and/or massive, or performance of therapeutic procedures to control them.
2 secondary outcomes
Other significant clinical events
Time frame: 12-month follow-up period after inclusion
Changes in quality of life
Time frame: 12-month follow-up period after inclusion
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 17 Mar 2025.
- Background: PubMed 36079173Viteri-Noel A, Gonzalez-Garcia A, Patier JL, Fabregate M, Bara-Ledesma N, Lopez-Rodriguez M, Gomez Del Olmo V, Manzano L. Hereditary Hemorrhagic Telangiectasia: Genetics, Pathophysiology, Diagnosis, and Management. J Clin Med. 2022 Sep 5;11(17):5245. doi: 10.3390/jcm11175245.
- Background: PubMed 32503579Sanchez-Martinez R, Iriarte A, Mora-Lujan JM, Patier JL, Lopez-Wolf D, Ojeda A, Torralba MA, Juyol MC, Gil R, Anon S, Salazar-Mendiguchia J, Riera-Mestre A; RiHHTa Investigators of the Rare Diseases Working Group from the Spanish Society of Internal Medicine. Current HHT genetic overview in Spain and its phenotypic correlation: data from RiHHTa registry. Orphanet J Rare Dis. 2020 Jun 5;15(1):138. doi: 10.1186/s13023-020-01422-8.
- Background: PubMed 31360828Albinana V, Gimenez-Gallego G, Garcia-Mato A, Palacios P, Recio-Poveda L, Cuesta AM, Patier JL, Botella LM. Topically Applied Etamsylate: A New Orphan Drug for HHT-Derived Epistaxis (Antiangiogenesis through FGF Pathway Inhibition). TH Open. 2019 Jul 26;3(3):e230-e243. doi: 10.1055/s-0039-1693710. eCollection 2019 Jul.
- The Multisystemic Diseases Group encompasses several lines of research related to pathologies that involve complex clinical management that usually falls within the scope of Internal Medicine.Link provided by the sponsor.
- Individual participant dataSharing planned: Undecided
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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.
José Luis Patier, MD principal investigator
Hospital Universitario Ramon y Cajal
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 Hereditary Hemorrhagic Telangiectasia and HHT, run by Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal at 1 site in Spain.
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 4 inclusion and 7 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 17 Mar 2025. 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 Spain. 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?
Hemorrhagic clinical events (time frame: 12-month follow-up period after inclusion). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05550376, which also lists 3 linked publications.
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 17 Mar 2025.