Influence of Hypoxic Induced Factors in Patients With Hereditary Hemorrhagic Telangiectasia

Hereditary Hemorrhagic Telangiectasia Clinical Trial

Official title:

Influence of Hypoxic Induced Factors in Patients With Hereditary Hemorrhagic Telangiectasia (HHT)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04469517
• Other study ID #: HIF in HHT
• Status: Recruiting
• Start date: August 10, 2020
• Est. completion date: October 1, 2024

Study information

• Verified date: July 2023
• Source: University Hospital, Essen
• Contact: Freya Droege, MD
• Phone: 0049201 723
• Email: freya.droege[@]uk-essen.de
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: October 1, 2024
• Est. primary completion date: June 30, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Hereditary Hemorrhagic Telangiectasia
• Telangiectasia, Hereditary Hemorrhagic
• Telangiectasis

Intervention

Other:
• hypoxic induced factors
hypoxic induced factors analyzed in blood sample

Locations

Country	Name	City	State
Germany	University Hospital Essen	Essen	NRW

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Essen

Country where clinical trial is conducted

Germany, 

References & Publications (5)

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. — View 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. — View 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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Differences in hypoxic induced factors	Differences in hypoxic induced factors analyzed in blood samples from patients with HHT and healthy controls	12 months
Secondary	Correlation of level of hypoxic induced factors and disease severity	Correlation of level of hypoxic induced factors in patients' blood sample and their disease severity	12 months