Genotype Expression and Phenotype of Endothelial Cells, Carrying an ACVRL1, ENG or SMAD4 Mutation, in Response to BMP9 for the Identification of New Therapeutic Targets in Hereditary Haemorrhagic Telangiectasia

Hereditary hemorrhagic telangiectasia (HHT) or Osler-Weber-Rendu syndrome patients are carriers of a heterozygous mutation of the activin receptor-like kinase 1 (ACVRL1), Endoglin (ENG) or Mothers against decapentaplegic homolog 4 (SMAD4) gene. HHT involves the Bone Morphogenetic Protein 9 (BMP9)/Activin receptor-Like Kinase 1 (ALK1)-endoglin signalling pathway. BMP9 is a growth factor that binds to ALK1 receptor and to endoglin its co-receptors and physiologically activates Smad signaling pathway. Endothelial cells in HHT patients display half expression of functional ALK1 receptors or endoglin co-receptors or of the transcription factor SMAD4, which should lead to effects on the functions of these cells.

The identification of differences in gene expression between endothelial cells from HHT patients and healthy donors will allow the identification of new functions or new target pathways for therapy. Circulating endothelial cells are rare in the bloodstream in adults, but are present in greater quantities in cord blood.

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Key information

Conditions

Hereditary Haemorrhagic Telangiectasia Cardiovascular Abnormalities Cardiovascular Diseases Congenital Abnormalities Congenital, Hereditary, and Neonatal Diseases and Abnormalities Hematologic Diseases Hemic and Lymphatic Diseases Hemorrhagic Disorders Hemostatic Disorders Telangiectasia, Hereditary Hemorrhagic Telangiectasis Vascular Diseases Vascular Malformations

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Hôpital Femme-mère-Enfant, Bron, France

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

Newborn whose parents :

are adults
are affiliated to a social security or similar
are not subject to any legal protection measures
Newborn child with one parent who has monitored for HHT confirmed by molecular biology (carrier of a mutation of the SMAD4, ENG or ACVRL1 gene).
Consent signed by the two representatives of parental authority

Exclusion criteria

One of the two parents opposes donating the umbilical cord blood and the umbilical cord for research
One of the two parents opposes genetic testing
Patient for whom it was not possible to obtain umbilical cord blood after delivery for technical or medical reasons.

Treatment and study plan

Cord blood sampling

Biological

Collection of 2 milliliters (mL) of cord blood on an Ethylenediaminetetraacetic acid (EDTA) tube, on the day of delivery and after cutting the umbilical cord, for genetic testing

Cord sampling

Biological

Collection of 20 centimeters (cm) of umbilical cord

Primary outcomes

Number of Endothelial Colony Forming Cells (ECFC) from cord blood

Time frame: up to 3 weeks after cells isolation

The primary outcome is the obtention of at least one clone of 10 000 cells from the cord blood after 3 weeks from the time of isolation. Number of viable cells is measured by Trypan blue test.
Number of Human Umbilical Vein Endothelial Cells(HUVEC) from cord

Time frame: up to one week

For the cord, the primary outcome is the obtention of 500 000 cells after one week from the isolation. Number of viable cells is measured by Trypan blue test.

Secondary outcomes

cell freezing and thawing

Time frame: Through study completion, an average of 5 years.

After isolation and amplification, cells from cord or from clones from the cord blood are frozen in vials. The cells viability (50 to 70% of alive cells after thawing) is a criteria of successful experiment.
Gene expression quantification after RNA extraction from cells

Time frame: Through study completion, an average of 5 years.

The third outcome is reached when we obtain up to 5 µg of RNA after cell seeding and stimulation with growth factors. Gene expression is measured by real-time polymerase chain reaction (RT-qPCR) and Ribonucleic acid Sequencing (RNAseq).

Sponsors and collaborators

Lead sponsor

Hospices Civils de Lyon

Other

Registry information

Acronym: CAERO

Important dates

Study start: 2023
Primary completion: 2023
Study completion: 2023
First posted: Nov 30, 2022
Registry last updated: Sep 3, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Published trials that share one or more normalized conditions with this study.

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