Clinical trial NCT04469517: Influence of Hypoxic Induced Factors in Patients With Hereditary Hemorrhagic Telangiectasia
Official title: Influence of Hypoxic Induced Factors in Patients With Hereditary Hemorrhagic Telangiectasia (HHT)
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Hereditary Hemorrhagic Telangiectasia
Keywords: hereditary hemorrhagic telangiectasia
Lead sponsor: University Hospital, Essen
Sponsor class: OTHER
First posted: 2020-07-14
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with diagnosed hereditary hemorrhagic telangiectasie (HHT)

Brief summary: Patients with hereditary hemorrhagic telangiectasia (HHT) suffer from an inherited disorder leading to systemic vascular malformations. Mutations in several genes of the transforming growth factor (TGF)-β superfamily pathway influence angiogenesis in patients with HHT. The genetic loss of ALK1 or ENG alone are not sufficient to induce AVMs; environmental insults that could trigger angiogenesis (e.g. wounding) are also needed. In this study it will be analyzed if hypoxic induced factors could have an influence on the disease HHT.

Detailed description: Hereditary hemorrhagic telangiectasia (HHT) is characterized by systemic vascular malformations leading to recurrent bleedings and shunt formation especially in the liver, lungs and the brain. The underlying pathogenic HHT mechanism remains unclear. The wide variability in age of onset and severity of symptoms amongst patients, even within the same family, suggests several factors contribute to the complexity of this disease. Mutations in several genes of the transforming growth factor (TGF)-β superfamily pathway influence angiogenesis in patients with HHT. The genetic loss of ALK1 or ENG alone are not sufficient to induce AVMs; environmental insults that could trigger angiogenesis (e.g. wounding) are also needed. In this study it will be analyzed if hypoxic induced factors could have an influence on the disease HHT.

Eligibility criteria: Inclusion Criteria:

* diagnosed HHT (genetic testing and/ or fulfill at least 3 Curacao Criteria)
* older than 17 years
* ability to consent

Exclusion Criteria:

* if inclusion Criteria are not met

Primary outcomes:
measure: Differences in hypoxic induced factors
timeFrame: 12 months
Secondary outcomes:
measure: Correlation of level of hypoxic induced factors and disease severity
timeFrame: 12 months
Other outcomes:
Locations:
city: Essen
country: Germany
facility: University Hospital Essen
state: NRW
Study officials:
affiliation: University hospital Essen Otorhinolaryngology, Hufelandstr. 55, 45147 Essen, Germany
name: Freya Droege, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Kjeldsen AD, Vase P, Green A. [Hereditary hemorrhagic telangiectasia. A population-based study on prevalence and mortality among Danish HHT patients]. Ugeskr Laeger. 2000 Jun 19;162(25):3597-601. Danish.
citation: Shovlin CL, Guttmacher AE, Buscarini E, Faughnan ME, Hyland RH, Westermann CJ, Kjeldsen AD, Plauchu H. Diagnostic criteria for hereditary hemorrhagic telangiectasia (Rendu-Osler-Weber syndrome). Am J Med Genet. 2000 Mar 6;91(1):66-7. doi: 10.1002/(sici)1096-8628(20000306)91:13.0.co;2-p.
citation: Sanchez-Elsner T, Botella LM, Velasco B, Corbi A, Attisano L, Bernabeu C. Synergistic cooperation between hypoxia and transforming growth factor-beta pathways on human vascular endothelial growth factor gene expression. J Biol Chem. 2001 Oct 19;276(42):38527-35. doi: 10.1074/jbc.M104536200. Epub 2001 Aug 2.
citation: Park SO, Wankhede M, Lee YJ, Choi EJ, Fliess N, Choe SW, Oh SH, Walter G, Raizada MK, Sorg BS, Oh SP. Real-time imaging of de novo arteriovenous malformation in a mouse model of hereditary hemorrhagic telangiectasia. J Clin Invest. 2009 Nov;119(11):3487-96. doi: 10.1172/JCI39482. Epub 2009 Oct 1.
citation: Attisano L, Wrana JL. Smads as transcriptional co-modulators. Curr Opin Cell Biol. 2000 Apr;12(2):235-43. doi: 10.1016/s0955-0674(99)00081-2.