Clinical trial NCT05550376: Genotype-phenotype Association in Hereditary Hemorrhagic Telangiectasia
Official title: Genotype-phenotype Association Study of ENG and ACVRL1 Genes in the Inflammatory and Endothelial Response in Hereditary Hemorrhagic Telangiectasia (HHT)
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Hereditary Hemorrhagic Telangiectasia
HHT
Rendu Osler Weber Disease
Keywords: Hereditary Hemorrhagic Telangiectasia
HHT
Rendu Osler Weber Disease
Genotype-phenotype association
ENG
ALK-1
Lead sponsor: Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal
Sponsor class: OTHER
Collaborators: name: Sociedad Española De Medicina Interna
First posted: 2022-09-22
Enrollment: 85
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Hemorrhagic clinical events
timeFrame: 12-month follow-up period after inclusion
Secondary outcomes:
measure: Other significant clinical events
timeFrame: 12-month follow-up period after inclusion
measure: Changes in quality of life
timeFrame: 12-month follow-up period after inclusion
Other outcomes:
Locations:
city: Madrid
country: Spain
facility: Hospital Universitario Ramón y Cajal
Study officials:
affiliation: Hospital Universitario Ramón y Cajal
name: José Luis Patier, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.