Immunological Effects of Iron Supplementation in HHT Disease

Status: Recruiting
Location: See location...
Intervention Type: Biological
Study Type: Interventional
Study Phase: Not Applicable
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. 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.

Eligibility
Participation Requirements
Sex: All
Minimum Age: 18
Maximum Age: 99
Healthy Volunteers: f
View:

• 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.

⁃ 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

Locations
Other Locations
France
Hôpital Femme-Mère-Enfant
RECRUITING
Bron
Contact Information
Primary
Alexandre Guilhem, MD
alexandre.guilhem@chu-lyon.fr
04 27 85 50 40
Time Frame
Start Date: 2025-09-24
Estimated Completion Date: 2028-12-31
Participants
Target number of participants: 155
Treatments
Experimental: No iron deficiency - no treatment
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
Experimental: No iron deficiency under iron treatment
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.
Experimental: Iron deficiency
Patient with ferritin \< 25µg/L No iron supplementation or RBC transfusion over the past 3 months
Sponsors
Leads: Hospices Civils de Lyon

This content was sourced from clinicaltrials.gov