Hereditary Haemorrhagic TelangiectasiaCAERONCT05632484
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
A study testing Cord blood sampling and Cord sampling in people with Hereditary Haemorrhagic Telangiectasia, run by Hospices Civils de Lyon at 3 sites in France.
Trial summary
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. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Hereditary Haemorrhagic Telangiectasia
- What is being tested?
- Cord blood sampling and Cord sampling
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- 3 sitesFrance
- Study dates
- 10 Mar 2023to 20 May 2023
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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.
Trial locations and contacts
3 sites in 1 country.
France3 sites
Hôpital Femme-mère-Enfant
Bron, 69677
Hôpital Estaing
Clermont-Ferrand, 63100
Hôpital St Eloi
Montpellier, 34295
About this study
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.
- Conditions
- Hereditary Haemorrhagic Telangiectasia
- Being tested
- Cord blood sampling, Cord sampling
- Keywords
- hereditary haemorrhagic telangiectasia, endothelial cell
- Medical subject headings
- Telangiectasia, Hereditary Hemorrhagic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cord blood samplingBiological
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 blood samplingBiological
Collection of 50 to 100 mL of cord blood from the cord blood collection bag
Cord samplingBiological
Collection of 20 centimeters (cm) of umbilical cord
| Study group | Role | What they receive |
|---|---|---|
| Newborns with a parent with HHT disease | Experimental | 16 newborns with one parent suffering HHT disease and carrying a mutation in the ACVRL1, ENG or SMAD4 gene will be included in this study. Receives: Biological: Cord blood sampling; Biological: Cord sampling |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Endothelial Colony Forming Cells (ECFC) from cord blood
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.
Measured: up to 3 weeks after cells isolation
Number of Human Umbilical Vein Endothelial Cells(HUVEC) from cord
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.
Measured: up to one week
Secondary outcomes (2)
cell freezing and thawing
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.
Measured: Through study completion, an average of 5 years.
Gene expression quantification after RNA extraction from cells
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).
Measured: Through study completion, an average of 5 years.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Nov 2022
- Study start10 Mar 2023
- Primary completion20 May 2023
- Study completion20 May 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Hereditary Haemorrhagic TelangiectasiaStudies of the same condition, open and under way.
- More trials run by Hospices Civils de LyonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hospices Civils de Lyon
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05632484
- Sponsor's protocol ID
- 69HCL20_0250
- Other IDs
- 2021-A01792-39
- Acronym
- CAERO
- Status last verified
- Aug 2025
- First submitted
- 21 Oct 2022
- Last updated
- 3 Sep 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Al Tabosh T, Al Tarrass M, Tourvieilhe L, Guilhem A, Dupuis-Girod S, Bailly S. Hereditary hemorrhagic telangiectasia: from signaling insights to therapeutic advances. J Clin Invest. 2024 Feb 15;134(4):e176379. doi: 10.1172/JCI176379.
PubMed 38357927Al Tabosh T, Liu H, Koca D, Al Tarrass M, Tu L, Giraud S, Delagrange L, Beaudoin M, Riviere S, Grobost V, Rondeau-Lutz M, Dupuis O, Ricard N, Tillet E, Machillot P, Salomon A, Picart C, Battail C, Dupuis-Girod S, Guignabert C, Desroches-Castan A, Bailly S. Impact of heterozygous ALK1 mutations on the transcriptomic response to BMP9 and BMP10 in endothelial cells from hereditary hemorrhagic telangiectasia and pulmonary arterial hypertension donors. Angiogenesis. 2024 May;27(2):211-227. doi: 10.1007/s10456-023-09902-8. Epub 2024 Jan 31.
PubMed 38294582
Study at a glance
From the registry record, last updated by the sponsor on 3 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT05632484
- Acronym / sponsor ID
- CAERO / 69HCL20_0250
- Conditions
- Hereditary Haemorrhagic Telangiectasia
- Keywords
- hereditary haemorrhagic telangiectasia, endothelial cell
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 16 participants (actual)
- Lead sponsor
- Hospices Civils de LyonUniversity, hospital or other
- Study start
- 10 Mar 2023 (actual)
- Primary completion
- 20 May 2023 (actual)
- Study completion
- 20 May 2023 (actual)
- First posted
- 30 Nov 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Newborns with a parent with HHT disease | Experimental | Biological: Cord blood sampling, Biological: Cord sampling16 newborns with one parent suffering HHT disease and carrying a mutation in the ACVRL1, ENG or SMAD4 gene will be included in this study. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (6 listed)
- Newborn whose parents :
- 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
Key exclusion criteria (3 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Cord blood samplingCollection 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 | Biological | Newborns with a parent with HHT disease |
| Cord blood samplingCollection of 50 to 100 mL of cord blood from the cord blood collection bag | Biological | Newborns with a parent with HHT disease |
| Cord samplingCollection of 20 centimeters (cm) of umbilical cord | Biological | Newborns with a parent with HHT disease |
Primary outcome
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.
2 secondary outcomes
cell freezing and thawing
Time frame: Through study completion, an average of 5 years.
Gene expression quantification after RNA extraction from cells
Time frame: Through study completion, an average of 5 years.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Sep 2025.
- Results publication: PubMed 38357927Al Tabosh T, Al Tarrass M, Tourvieilhe L, Guilhem A, Dupuis-Girod S, Bailly S. Hereditary hemorrhagic telangiectasia: from signaling insights to therapeutic advances. J Clin Invest. 2024 Feb 15;134(4):e176379. doi: 10.1172/JCI176379.
- Results publication: PubMed 38294582Al Tabosh T, Liu H, Koca D, Al Tarrass M, Tu L, Giraud S, Delagrange L, Beaudoin M, Riviere S, Grobost V, Rondeau-Lutz M, Dupuis O, Ricard N, Tillet E, Machillot P, Salomon A, Picart C, Battail C, Dupuis-Girod S, Guignabert C, Desroches-Castan A, Bailly S. Impact of heterozygous ALK1 mutations on the transcriptomic response to BMP9 and BMP10 in endothelial cells from hereditary hemorrhagic telangiectasia and pulmonary arterial hypertension donors. Angiogenesis. 2024 May;27(2):211-227. doi: 10.1007/s10456-023-09902-8. Epub 2024 Jan 31.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Cord blood sampling and Cord sampling in people with Hereditary Haemorrhagic Telangiectasia, run by Hospices Civils de Lyon at 3 sites in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 3 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Endothelial Colony Forming Cells (ECFC) from cord blood (time frame: up to 3 weeks after cells isolation). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05632484, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Sep 2025.