Influence of Hypoxic Induced Factors in Patients With Hereditary Hemorrhagic Telangiectasia

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

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.

Study Overview

• Status: Recruiting
• Conditions: Hereditary Hemorrhagic Telangiectasia
• Intervention / Treatment: Other: hypoxic induced factors

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 Type: Observational
• Enrollment (Estimated): 100

Contacts and Locations

• Study Contact: Name: Freya Droege, MD; Phone Number: 2481 0049201 723; Email: freya.droege@uk-essen.de
• Study Contact Backup: Name: Anna Wrobeln, PhD; Phone Number: 4646 0049201 723; Email: anna.wrobeln@uk-essen.de

Study Locations

• Germany
  • NRW
    • Essen, NRW, Germany, 45147
      • Recruiting
      • University Hospital Essen
      • Contact: Freya Droege, MD; Phone Number: 2481 0049201723; Email: freya.droege@uk-essen.de

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Patients with diagnosed hereditary hemorrhagic telangiectasie (HHT)

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Differences in hypoxic induced factors	Differences in hypoxic induced factors analyzed in blood samples from patients with HHT and healthy controls	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Collaborators and Investigators

• Sponsor: University Hospital, Essen
• Investigators: Principal Investigator: Freya Droege, MD, University hospital Essen Otorhinolaryngology, Hufelandstr. 55, 45147 Essen, Germany

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): August 10, 2020
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): October 1, 2026

Study Registration Dates

• First Submitted: July 8, 2020
• First Submitted That Met QC Criteria: July 8, 2020
• First Posted (Actual): July 14, 2020

Study Record Updates

• Last Update Posted (Actual): December 6, 2024
• Last Update Submitted That Met QC Criteria: December 5, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Keywords: hereditary hemorrhagic telangiectasia
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Hematologic Diseases; Congenital Abnormalities; Cardiovascular Abnormalities; Hemostatic Disorders; Hemorrhagic Disorders; Vascular Malformations; Telangiectasis; Telangiectasia, Hereditary Hemorrhagic
• Other Study ID Numbers: HIF in HHT

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No