Generate-HHT: Genotype-phenotype Association in Hereditary Hemorrhagic Telangiectasia
Study Details
Study Description
Brief 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 interleukines, adhesion molecules, chemokines and immune regulatory molecules between both HHT groups.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
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
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| HHT1 Mutations in the ENG (endoglin) gene |
Other: Registry
Non-interventional registry
|
| HHT2 Mutations in the ALK-1 (activin receptor-like kinase) gene |
Other: Registry
Non-interventional registry
|
Outcome Measures
Primary Outcome Measures
- Hemorrhagic clinical events [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.
Secondary Outcome Measures
- Other significant clinical events [12-month follow-up period after inclusion]
Significant clinical events other than hemorrhagic episodes (e.g., infections, neoplasms or other severe diseases)
- Changes in quality of life [12-month follow-up period after inclusion]
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).
Eligibility Criteria
Criteria
Inclusion Criteria:
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Age between 18 and 75 years.
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Confirmed diagnosis of HHT, according to the Curaçao criteria or genetic diagnosis.
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Clinically stable condition at the time of inclusion, defined as score < 7 points on the Epistaxis Severity Score (ESS).
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Having signed the informed consent, after having received all the information concerning the study.
Exclusion Criteria:
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Major coronary or cerebrovascular event in the 3 months prior to inclusion.
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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.
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Major surgery during the 2 months prior to inclusion.
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Pharmacological treatment maintained during the 3 months prior to inclusion with NSAIDs, corticosteroids or chemotherapy.
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Toxic habits, including severe smoking, alcohol or drug abuse, which in the opinion of the investigator could interfere with the conduct of the study.
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Pregnancy or puerperium.
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Any other condition that limits compliance with the visits or procedures established in the protocol.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Hospital Universitario Ramón y Cajal | Madrid | Spain | 28034 |
Sponsors and Collaborators
- Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal
- Sociedad Española De Medicina Interna
Investigators
- Principal Investigator: José Luis Patier, MD, Hospital Universitario Ramón y Cajal
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
- Albinana 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.
- Sanchez-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.
- 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.
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