Studies of White Blood Cells Derived From HHT Patients

NCT ID: NCT00230633

Last Updated: 2023-09-28

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Total Enrollment

200 participants

Study Classification

OBSERVATIONAL

Study Start Date

2002-04-30

Study Completion Date

2026-10-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Telangiectasia, Hereditary Hemorrhagic

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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Patients with HHT

People with molecularly confirmed HHT. No intervention, blood sample only

No interventions assigned to this group

Controls

People without HHT No intervention, blood sample only

No interventions assigned to this group

Eligibility Criteria

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Inclusion Criteria

* Patients with HHT,
* HHT patients family members

Exclusion Criteria

* Unable to provide informed consent
Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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British Heart Foundation

OTHER

Sponsor Role collaborator

Imperial College London

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Claire L Shovlin

Role: PRINCIPAL_INVESTIGATOR

Imperial College London

Locations

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Imperial College Hammersmith Campus

London, , United Kingdom

Site Status

Countries

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United Kingdom

References

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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.

Reference Type BACKGROUND
PMID: 32303606 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 34904380 (View on PubMed)

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.

Reference Type RESULT
PMID: 18000608 (View on PubMed)

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 deficiency and platelets. PLoS One. 2014 Feb 19;9(2):e88812. doi: 10.1371/journal.pone.0088812. eCollection 2014.

Reference Type RESULT
PMID: 24586400 (View on PubMed)

Other Identifiers

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IC/CLS3

Identifier Type: -

Identifier Source: org_study_id

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