Genotype-phenotype Association in Hereditary Hemorrhagic Telangiectasia

Completed

• Conditions: Rendu Osler Weber Disease; Hereditary Hemorrhagic Telangiectasia; HHT
• Interventions: Other: Registry

• Registration Number: NCT05550376
• Lead Sponsor: Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal

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.

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 Timeline

• Study Start: 2021-04-30
• Study First Submitted: 2022-09-19
• Study First Submitted QC: 2022-09-19
• Study First Posted: 2022-09-22
• Primary Completion: 2023-12-31
• Study Completion: 2023-12-31
• Status Verified: 2025-03
• Last Update Submitted: 2025-03-14
• Last Update Posted: 2025-03-17

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 85

Inclusion Criteria

• 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.

Exclusion Criteria

• 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.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
HHT2	Registry	Mutations in the ALK-1 (activin receptor-like kinase) gene
HHT1	Registry	Mutations in the ENG (endoglin) gene

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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).

Trial Locations

Locations (1)

Hospital Universitario Ramón y Cajal; 🇪🇸 Madrid, Spain