Influence of Hypoxic Induced Factors in Patients With Hereditary Hemorrhagic Telangiectasia
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| HHT patients with HHT |
Other: hypoxic induced factors
hypoxic induced factors analyzed in blood sample
|
| control persons age- and sex matched who do not suffer from HHT nor their first or second degree relatives |
Other: hypoxic induced factors
hypoxic induced factors analyzed in blood sample
|
Outcome Measures
Primary Outcome Measures
- Differences in hypoxic induced factors [12 months]
Differences in hypoxic induced factors analyzed in blood samples from patients with HHT and healthy controls
Secondary Outcome Measures
- Correlation of level of hypoxic induced factors and disease severity [12 months]
Correlation of level of hypoxic induced factors in patients' blood sample and their disease severity
Eligibility Criteria
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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University Hospital Essen | Essen | NRW | Germany | 45147 |
Sponsors and Collaborators
- University Hospital, Essen
Investigators
- Principal Investigator: Freya Droege, MD, University hospital Essen Otorhinolaryngology, Hufelandstr. 55, 45147 Essen, Germany
Study Documents (Full-Text)
None provided.More Information
Publications
- Attisano L, Wrana JL. Smads as transcriptional co-modulators. Curr Opin Cell Biol. 2000 Apr;12(2):235-43. Review.
- 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.
- 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.
- Sánchez-Elsner T, Botella LM, Velasco B, Corbí A, Attisano L, Bernabéu 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. Epub 2001 Aug 2.
- 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.
- HIF in HHT