Immunological Effects of Iron Supplementation in HHT Disease

NCT07111598 | Recruiting

• 1 other identifier: 69HCL24_0724
• Study Type: interventional
• Target: 155
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Hereditary Haemorrhagic Telangiectasia

Keywords

Hereditary haemorrhagic telangiectasia (HHT); iron supplementation; lymphopenia

Outcome Measures

Primary Outcomes (1)

• 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.

  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).

  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).

  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).

  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).

  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).

  Baseline for all the 3 groups and 3 months after iron supplementation for group 3.

Study Arms (3)

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

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.

Biological: Blood test at D0

Iron deficiency

EXPERIMENTAL

Patient with ferritin \< 25µg/L No iron supplementation or RBC transfusion over the past 3 months

Biological: Blood test at D0; Biological: Blood test at D+3 months

Interventions

Blood test at D0 BIOLOGICAL

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

Iron deficiency; No iron deficiency - no treatment; No iron deficiency under iron treatment

Blood test at D+3 months BIOLOGICAL

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

Iron deficiency

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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

You may not qualify if:

• 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.
• 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).

Sponsors & Collaborators

• Hospices Civils de Lyon: lead

Study Sites (1)

Hôpital Femme-Mère-Enfant

Bron, Rhone, 69500, France

RECRUITING

MeSH Terms

Conditions

Telangiectasia, Hereditary Hemorrhagic; Lymphopenia

Condition Hierarchy (Ancestors)

Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Telangiectasis; Hemorrhagic Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Vascular Malformations; Cardiovascular Abnormalities; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Leukopenia; Cytopenia; Leukocyte Disorders; Immunologic Deficiency Syndromes; Immune System Diseases

Central Study Contacts

Alexandre Guilhem, MD

CONTACT

04 27 85 50 40; alexandre.guilhem@chu-lyon.fr

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: HEALTH SERVICES RESEARCH
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: July 31, 2025
• First Posted: August 8, 2025
• Study Start: September 24, 2025
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 31, 2028
• Last Updated: October 3, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)