Hereditary Haemorrhagic TelangiectasiaFer&RONCT07111598
Immunological Effects of Iron Supplementation in HHT Disease
A study testing Blood test at D0 and Blood test at D+3 months in people with Hereditary Haemorrhagic Telangiectasia, run by Hospices Civils de Lyon at 1 site in France.
Trial summary
Hereditary haemorrhagic telangiectasia (HHT), is a rare genetic vascular disorder with autosomal dominant inheritance. Its prevalence is estimated at approximately 1 in 6,000 individuals in France. Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- Hereditary Haemorrhagic Telangiectasia
- What is being tested?
- Blood test at D0 and Blood test at D+3 months
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 155 participants
- Where
- 1 siteFrance
- Study dates
- 24 Sep 2025to 31 Dec 2028
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
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 18 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- For all three groups:
- Adult patient diagnosed with HHT (meeting 3 or 4 Curaçao criteria).
- Documented pathogenic mutation in one of the following genes: ENG, ACVRL1, or MADH4.
- Patient enrolled in the CIROCO cohort.
- Written informed consent freely given and signed by the patient.
- Patient covered by a social security scheme or equivalent.
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- Routine biological follow-up for HHT performed within the 15 days preceding the inclusion visit (complete blood count, reticulocytes, ferritin, CRP, calcium, phosphorus).
- Specific to Group 1:
- Ferritin > 25 µg/L
- No iron supplementation (oral or intravenous) in the past 3 months
- No red blood cell transfusion in the past 3 months
- Specific to Group 2:
- Ferritin > 25 µg/L
- Ongoing oral iron therapy, or at least one intravenous iron infusion, or at least one red blood cell transfusion within the past 3 months
- Specific to Group 3:
- Ferritin < 25 µg/L
- No iron supplementation (oral or intravenous) in the past 3 months
- No red blood cell transfusion in the past 3 months
Who cannot join
- Patients with hemoglobin levels < 90 g/L.
- Patients with active cancer or recent cancer remission (< 3 months) that may alter the immune profile.
- Patients with an active infection or recent infection recovery (< 3 months) that may alter the immune profile.
- Patients with an autoimmune or autoinflammatory disease, either active or recently treated (< 3 months), requiring immunosuppressive therapy and potentially altering the immune profile.
- Pregnant, postpartum, or breastfeeding women.
- Minors.
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- Individuals deprived of liberty by judicial or administrative decision.
- Individuals undergoing psychiatric care.
- Individuals admitted to a healthcare or social institution for reasons other than research participation.
- Adults under legal protection (guardianship, curatorship).
- Individuals participating in another interventional clinical trial with an exclusion period still in effect at the time of pre-inclusion.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
France1 site, 1 recruiting
- Recruiting
Hôpital Femme-Mère-Enfant
Bron, Rhone, 69500
Alexandre Guilhem, MD, 04 27 85 50 40 ext. +33, alexandre.guilhem@chu-lyon.fr
About this study
Hereditary haemorrhagic telangiectasia (HHT), is a rare genetic vascular disorder with autosomal dominant inheritance. Its prevalence is estimated at approximately 1 in 6,000 individuals in France. Clinical manifestations include recurrent nosebleeds (epistaxis), cutaneous telangiectasias, and visceral arteriovenous malformations (AVMs) that may affect the lungs, gastrointestinal tract, liver, and brain.
Beyond vascular abnormalities, patients often present with a decrease in circulating T lymphocytes (T-cell lymphopenia), which can be profound but remains unexplained. There is also a distinct infectious risk profile associated with the disease: brain abscesses in the presence of pulmonary AVMs (pAVMs), and osteoarticular infections in patients with the longest durations of epistaxis. However, no definitive correlation has been established between T-cell lymphopenia and infection risk.
Read more
Iron-deficiency anemia is a frequent complication in HHT, affecting about 50% of patients, with a mean age of onset around 36 years. Its prevalence increases with age. These patients typically require prolonged and high-dose iron supplementation, administered either orally or intravenously, which may expose them to side effects not observed in other clinical contexts. In a previous study, we identified a correlation between the level of iron supplementation (none, oral, or intravenous) and the severity of T-cell lymphopenia.
This association may be explained by two potential mechanisms linking iron metabolism to immune function:
- A direct toxic effect of iron on immune system homeostasis
- Impaired lymphocyte production resulting from iron deficiency, with the type of supplementation serving as an indirect marker of deficiency severity We propose a prospective study designed to differentiate between these two hypotheses. The aim of the study is to characterize the impact of iron deficiency and iron supplementation on the immune system of patients with HHT.
- Conditions
- Hereditary Haemorrhagic Telangiectasia
- Being tested
- Blood test at D0, Blood test at D+3 months
- Keywords
- Hereditary haemorrhagic telangiectasia (HHT), iron supplementation, lymphopenia
- Medical subject headings
- Telangiectasia, Hereditary Hemorrhagic, Lymphopenia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Blood test at D0Biological
Six extra blood collection tubes (28 mL) will be drawn during the visit (D0), in addition to the routine blood samples, at the blood collection center
Blood test at D+3 monthsBiological
six extra blood collection tubes (28 mL) will be drawn during the visit (D+3 months) for group 3 patients, in addition to the routine blood samples, at the blood collection center
| Study group | Role | What they receive |
|---|---|---|
| No iron deficiency - no treatment | Experimental | Patients without iron deficiency with no need of iron supplementation. Ferritin > 25µg/L and no iron supplementation or red blood cell (RBC) transfusion over the past 3 months Receives: Biological: Blood test at D0 |
| No iron deficiency under iron treatment | Experimental | Patient without iron deficiency thanks to iron supplementation or RBC transfusion Ferritin > 25µg/L and ongoing or recent (within the past 3 months) iron supplementation or RBC transfusion. Receives: Biological: Blood test at D0 |
| Iron deficiency | Experimental | Patient with ferritin < 25µg/L No iron supplementation or RBC transfusion over the past 3 months Receives: Biological: Blood test at D0; Biological: Blood test at D+3 months |
What is being measured
The primary outcome is the main question the study is designed to answer.
Helper T-cell concentration (number of CD3⁺CD4⁺ lymphocytes per mm^³ of blood).
Samples will be analyzed by spectral cytometry to determine the concentration of each leukocyte population of interest.
Measured: Baseline for all the 3 groups and 3 months after iron supplementation for group 3.
Secondary outcomes (8)
Naive/effector memory/terminal effector memory/central memory helper T lymphocytes concentration (number per mm^³ of blood).
Samples will be analyzed by spectral cytometry to determine the concentration of each leukocyte population of interest.
Measured: Baseline for all the 3 groups and 3 months after iron supplementation for group 3.
Naive/effector memory/terminal effector memory/central memory cytotoxic T lymphocytes concentration (number per mm^³ of blood).
Samples will be analyzed by spectral cytometry to determine the concentration of each leukocyte population of interest.
Measured: Baseline for all the 3 groups and 3 months after iron supplementation for group 3.
γδ T cells, mucosal-associated invariant T (MAIT) cells, and natural killer T (NKT) cells concentration (number per mm^³ of blood).
Samples will be analyzed by spectral cytometry to determine the concentration of each leukocyte population of interest.
Measured: Baseline for all the 3 groups and 3 months after iron supplementation for group 3.
Natural killer (NK) cells concentration (number per mm^³ of blood).
Samples will be analyzed by spectral cytometry to determine the concentration of each leukocyte population of interest.
Measured: Baseline for all the 3 groups and 3 months after iron supplementation for group 3.
Naive/memory/class-switched B lymphocytes concentration (number per mm^³ of blood).
Samples will be analyzed by spectral cytometry to determine the concentration of each leukocyte population of interest.
Measured: Baseline for all the 3 groups and 3 months after iron supplementation for group 3.
Plasmablasts concentration (number per mm^³ of blood).
Samples will be analyzed by spectral cytometry to determine the concentration of each leukocyte population of interest.
Measured: Baseline for all the 3 groups and 3 months after iron supplementation for group 3.
Classical/intermediate/non-classical/Tie2⁺ monocytes concentration (number per mm^³ of blood).
Samples will be analyzed by spectral cytometry to determine the concentration of each leukocyte population of interest.
Measured: Baseline for all the 3 groups and 3 months after iron supplementation for group 3.
Myeloid and plasmacytoid dendritic cells concentration (number per mm^³ of blood).
Samples will be analyzed by spectral cytometry to determine the concentration of each leukocyte population of interest.
Measured: Baseline for all the 3 groups and 3 months after iron supplementation for group 3.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Aug 2025
- Study start24 Sep 2025
- Primary completion31 Dec 2028 (estimated)
- Study completion31 Dec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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
- Health services research
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- Patients will undergo the inclusion visit during a scheduled consultation at the HHT disease reference center in Lyon. Eligibility and exclusion criteria will be assessed at this visit by the principal investigator, based on blood test results obtained within 15 days prior to the consultation. In addition, six extra blood collection tubes will be drawn during the visit (D0), in addition to the routine blood samples., For patients in Groups 1 and 2, no follow-up visit will be scheduled. For patients in Group 3, iron supplementation will be administered as part of routine care within 14 days following inclusion, according to the patient's usual treatment protocol in terms of active compound, daily dosage, and treatment duration. A second consultation will be scheduled three months after inclusion (D+3 months) to assess the correction of iron deficiency and to collect six additional blood tubes for immunological analysis.
- Masking
- None (open label)
- Enrolment
- 155 participants (estimated)
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
- NCT07111598
- Sponsor's protocol ID
- 69HCL24_0724
- Acronym
- Fer&RO
- Status last verified
- Sep 2025
- First submitted
- 31 Jul 2025
- Last updated
- 3 Oct 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Oct 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Immunological Effects of Iron Supplementation in HHT Disease
- ClinicalTrials.gov ID
- NCT07111598
- Acronym / sponsor ID
- Fer&RO / 69HCL24_0724
- Conditions
- Hereditary Haemorrhagic Telangiectasia
- Keywords
- Hereditary haemorrhagic telangiectasia (HHT), iron supplementation, lymphopenia
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 155 participants (estimated)
- Lead sponsor
- Hospices Civils de LyonUniversity, hospital or other
- Study start
- 24 Sep 2025 (actual)
- Primary completion
- 31 Dec 2028 (estimated)
- Study completion
- 31 Dec 2028 (estimated)
- First posted
- 8 Aug 2025 (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 haemorrhagic telangiectasia (HHT), is a rare genetic vascular disorder with autosomal dominant inheritance. Its prevalence is estimated at approximately 1 in 6,000 individuals in France. Clinical manifestations include recurrent nosebleeds (epistaxis), cutaneous telangiectasias, and visceral arteriovenous malformations (AVMs) that may affect the lungs, gastrointestinal tract, liver, and brain.
Beyond vascular abnormalities, patients often present with a decrease in circulating T lymphocytes (T-cell lymphopenia), which can be profound but remains unexplained. There is also a distinct infectious risk profile associated with the disease: brain abscesses in the presence of pulmonary AVMs (pAVMs), and osteoarticular infections in patients with the longest durations of epistaxis. However, no definitive correlation has been established between T-cell lymphopenia and infection risk.
Iron-deficiency anemia is a frequent complication in HHT, affecting about 50% of patients, with a mean age of onset around 36 years. Its prevalence increases with age. These patients typically require prolonged and high-dose iron supplementation, administered either orally or intravenously, which may expose them to side effects not observed in other clinical contexts. In a previous study, we identified a correlation between the level of iron supplementation (none, oral, or intravenous) and the severity of T-cell lymphopenia.
This association may be explained by two potential mechanisms linking iron metabolism to immune function:
- A direct toxic effect of iron on immune system homeostasis
- Impaired lymphocyte production resulting from iron deficiency, with the type of supplementation serving as an indirect marker of deficiency severity We propose a prospective study designed to differentiate between these two hypotheses. The aim of the study is to characterize the impact of iron deficiency and iron supplementation on the immune system of patients with HHT.
Study design
- Primary purpose
- Health services research
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
- Model description
- Patients will undergo the inclusion visit during a scheduled consultation at the HHT disease reference center in Lyon. Eligibility and exclusion criteria will be assessed at this visit by the principal investigator, based on blood test results obtained within 15 days prior to the consultation. In addition, six extra blood collection tubes will be drawn during the visit (D0), in addition to the routine blood samples., For patients in Groups 1 and 2, no follow-up visit will be scheduled. For patients in Group 3, iron supplementation will be administered as part of routine care within 14 days following inclusion, according to the patient's usual treatment protocol in terms of active compound, daily dosage, and treatment duration. A second consultation will be scheduled three months after inclusion (D+3 months) to assess the correction of iron deficiency and to collect six additional blood tubes for immunological analysis.
| Arm | Type | Receives |
|---|---|---|
| No iron deficiency - no treatment | Experimental | Biological: Blood test at D0Patients without iron deficiency with no need of iron supplementation. Ferritin > 25µg/L and no iron supplementation or red blood cell (RBC) transfusion over the past 3 months |
| No iron deficiency under iron treatment | Experimental | Biological: Blood test at D0Patient without iron deficiency thanks to iron supplementation or RBC transfusion Ferritin > 25µg/L and ongoing or recent (within the past 3 months) iron supplementation or RBC transfusion. |
| Iron deficiency | Experimental | Biological: Blood test at D0, Biological: Blood test at D+3 monthsPatient with ferritin < 25µg/L No iron supplementation or RBC transfusion over the past 3 months |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- For all three groups:
- Specific to Group 1:
- Specific to Group 2:
- Specific to Group 3:
Key exclusion criteria (11 listed)
- Patients with hemoglobin levels < 90 g/L.
- Patients with active cancer or recent cancer remission (< 3 months) that may alter the immune profile.
- Patients with an active infection or recent infection recovery (< 3 months) that may alter the immune profile.
- Patients with an autoimmune or autoinflammatory disease, either active or recently treated (< 3 months), requiring immunosuppressive therapy and potentially altering the immune profile.
- Pregnant, postpartum, or breastfeeding women.
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 |
|---|---|---|
| Blood test at D0Six extra blood collection tubes (28 mL) will be drawn during the visit (D0), in addition to the routine blood samples, at the blood collection center | Biological | Iron deficiency, No iron deficiency - no treatment, No iron deficiency under iron treatment |
| Blood test at D+3 monthssix extra blood collection tubes (28 mL) will be drawn during the visit (D+3 months) for group 3 patients, in addition to the routine blood samples, at the blood collection center | Biological | Iron deficiency |
Primary outcome
Helper T-cell concentration (number of CD3⁺CD4⁺ lymphocytes per mm^³ of blood).
Time frame: Baseline for all the 3 groups and 3 months after iron supplementation for group 3.
Samples will be analyzed by spectral cytometry to determine the concentration of each leukocyte population of interest.
8 secondary outcomes
Naive/effector memory/terminal effector memory/central memory helper T lymphocytes concentration (number per mm^³ of blood).
Time frame: Baseline for all the 3 groups and 3 months after iron supplementation for group 3.
Naive/effector memory/terminal effector memory/central memory cytotoxic T lymphocytes concentration (number per mm^³ of blood).
Time frame: Baseline for all the 3 groups and 3 months after iron supplementation for group 3.
γδ T cells, mucosal-associated invariant T (MAIT) cells, and natural killer T (NKT) cells concentration (number per mm^³ of blood).
Time frame: Baseline for all the 3 groups and 3 months after iron supplementation for group 3.
Natural killer (NK) cells concentration (number per mm^³ of blood).
Time frame: Baseline for all the 3 groups and 3 months after iron supplementation for group 3.
Naive/memory/class-switched B lymphocytes concentration (number per mm^³ of blood).
Time frame: Baseline for all the 3 groups and 3 months after iron supplementation for group 3.
Plasmablasts concentration (number per mm^³ of blood).
Time frame: Baseline for all the 3 groups and 3 months after iron supplementation for group 3.
Classical/intermediate/non-classical/Tie2⁺ monocytes concentration (number per mm^³ of blood).
Time frame: Baseline for all the 3 groups and 3 months after iron supplementation for group 3.
Myeloid and plasmacytoid dendritic cells concentration (number per mm^³ of blood).
Time frame: Baseline for all the 3 groups and 3 months after iron supplementation for group 3.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Oct 2025.
- Individual participant dataSharing planned: No
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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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Blood test at D0 and Blood test at D+3 months in people with Hereditary Haemorrhagic Telangiectasia, run by Hospices Civils de Lyon at 1 site 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 18 inclusion and 11 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: looking for participants now, as of the sponsor's last update on 3 Oct 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Alexandre Guilhem, MD (04 27 85 50 40 ext. +33, alexandre.guilhem@chu-lyon.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Helper T-cell concentration (number of CD3⁺CD4⁺ lymphocytes per mm^³ of blood). (time frame: Baseline for all the 3 groups and 3 months after iron supplementation for group 3.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 Oct 2025; AzTrials last refreshed its copy on 26 Oct 2026.