Studies of White Blood Cells Derived From HHT Patients

Telangiectasia, Hereditary Hemorrhagic Clinical Trial

Official title:

Studies of White Blood Cells Derived From HHT Patients

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00230633
• Other study ID #: IC/CLS3
• Status: Active, not recruiting
• Start date: April 2002
• Est. completion date: October 2026

Study information

• Verified date: September 2023
• Source: Imperial College London
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Hereditary Haemorrhagic Telangiectasia (HHT, also known as Osler-Weber-Rendu Syndrome) is an inherited vascular disease that leads to the development of dilated and fragile blood vessels. The study goal is to culture white blood cells that express the proteins mutated in HHT and examine in the laboratory to explain aspects of the HHT disease phenotype.

Description:

HHT is a vascular condition but many of the genes that are mutated to cause HHT (endoglin, ALK-1 and SMAD4) are also expressed in white blood cells. In this study, investigators will take blood samples from people with HHT, culture the white blood cells and study their properties in media prompting different types of differentiation, or infection of cell lines with Epstein Barr virus to provide cell lines which can be repeatedly studied. RNA and proteins will be extracted from these cells for study of white cell responses and association with expression levels of endoglin, ALK-1 and SMAD4. The investigators hypothesize that these cells which express "half-normal" endoglin, ALK-1 or SMAD4 will show differences when compared to normal white blood cells. It is also anticipated that that these findings may help to explain aspects of the HHT disease phenotype.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 200
• Est. completion date: October 2026
• Est. primary completion date: October 2026
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: N/A and older

Eligibility

Inclusion Criteria:

• Patients with HHT,
• HHT patients family members

Exclusion Criteria:

• Unable to provide informed consent

Related Conditions & MeSH terms

• Telangiectasia, Hereditary Hemorrhagic
• Telangiectasis

Locations

Country	Name	City	State
United Kingdom	Imperial College Hammersmith Campus	London

Sponsors (2)

Lead Sponsor	Collaborator
Imperial College London	British Heart Foundation

Country where clinical trial is conducted

United Kingdom, 

References & Publications (4)

Balachandar S, Graves TJ, Shimonty A, Kerr K, Kilner J, Xiao S, Slade R, Sroya M, Alikian M, Curetean E, Thomas E, McConnell VPM, McKee S, Boardman-Pretty F, Devereau A, Fowler TA, Caulfield MJ, Alton EW, Ferguson T, Redhead J, McKnight AJ, Thomas GA; Genomics England Research Consortium; Aldred MA, Shovlin CL. Identification and validation of a novel pathogenic variant in GDF2 (BMP9) responsible for hereditary hemorrhagic telangiectasia and pulmonary arteriovenous malformations. Am J Med Genet A. 2022 Mar;188(3):959-964. doi: 10.1002/ajmg.a.62584. Epub 2021 Dec 13. — View Citation

Clarke JM, Alikian M, Xiao S, Kasperaviciute D, Thomas E, Turbin I, Olupona K, Cifra E, Curetean E, Ferguson T, Redhead J; Genomics England Research Consortium; Shovlin CL. Low grade mosaicism in hereditary haemorrhagic telangiectasia identified by bidirectional whole genome sequencing reads through the 100,000 Genomes Project clinical diagnostic pipeline. J Med Genet. 2020 Dec;57(12):859-862. doi: 10.1136/jmedgenet-2019-106794. Epub 2020 Apr 17. No abstract available. — View Citation

Shovlin CL, Chamali B, Santhirapala V, Livesey JA, Angus G, Manning R, Laffan MA, Meek J, Tighe HC, Jackson JE. Ischaemic strokes in patients with pulmonary arteriovenous malformations and hereditary hemorrhagic telangiectasia: associations with iron defi — View Citation

Shovlin CL, Sulaiman NL, Govani FS, Jackson JE, Begbie ME. Elevated factor VIII in hereditary haemorrhagic telangiectasia (HHT): association with venous thromboembolism. Thromb Haemost. 2007 Nov;98(5):1031-9. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proteins and cellular markers related to coagulation	Not specified at outset. Blood samples will be collected over the recruitment period, usually on a single day. Analyses of biomarkers relate to the SAME DAY, within 24hs, though will be evaluated over subsequent months, on average completing in 1-5 years.	on average completing each biomarker study in 1-5 years