Clinical trial NCT05114278: Effect of Intravenous Iron Supplementation on Celiac Disease Remission (IRONCEL)
Official title: Effect of Intravenous Iron Supplementation on Celiac Disease Remission in Patients With Iron Deficiency and Intestinal Villous Atrophy: a Randomized Trial
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE4
Conditions: Celiac Disease
Keywords: Celiac disease
Iron deficiency
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
Collaborators: name: Ministry of Health, France
First posted: 2021-11-09
Enrollment: 204
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Phase IV, open, randomized, 2-arms parallel controlled trial with blinded assessment of end-point.
Primary purpose: TREATMENT

Brief summary: The study aims is to evaluate the efficacy of intravenous iron supplementation on celiac disease remission (total intestinal mucosal recovery). This randomized multicenter trial compare the administration of intravenous iron by infusion (Ferinject©: 15 mg/kg in NaCl solution in 30 min) and oral iron in combination; to patients receive only oral iron as standard care.

The first benefit with IV Iron supplementation is to correct iron deficiency more rapidly than oral iron alone because of trouble of absorption in case of intestinal villous atrophy.

Detailed description: Celiac disease is an autoimmune-like disorder induced in genetically predisposed individuals by dietary proteins from wheat (gluten). Its frequency reaches 1% in Europe.

In celiac patients, gluten induces small intestinal villous atrophy and, as a consequence, malnutrition. Celiac disease treatment relies on a long-life strict gluten-free diet that allows clinical and histological recovery and prevents long-term complications (autoimmune diseases, osteoporosis and malignancies). Remission is attested by total villous recovery on duodenal biopsy performed after one year of gluten free diet. Yet, in adults, systematic follow-up of biopsies for several years after gluten free diet initiation has recently revealed persistent villous atrophy in more than 40 % of cases with an increased risk in older patients (up to 56%). Lack of mucosal healing has been associated with the risk of complications in celiac, notably a risk factor for fractures and lymphoma. It is therefore necessary to define strategies to obtain and accelerate full recovery. Iron deficiency is strongly associated with celiac disease and is generally viewed as a consequence of small intestinal lesions and a symptom of malnutrition. Our preliminary clinical retrospective study showed more frequent iron deficiency anemia in celiac patients with (20/70; 29%) than without (11/88; 12.5%) villous atrophy (p = 0.015; OR: 2.78). Our previous experimental study suggests that iron deficiency may sustain tissue damage and delay mucosal recovery in celiac disease. Indeed the transferrin receptor (CD71) is overexpressed in the gut epithelium in case of iron deficiency and can interact with secretory IgA1 present in large amounts in the intestinal lumen of CD patients. Crosslinking of CD71 by polymeric IgA1 can induce production of inflammatory cytokines. Our working hypothesis is therefore that iron deficiency maintains aberrant expression of CD71 at the gut epithelial surface that sustains intestinal inflammation and epithelial damage. Iron supplementation of celiac patients with villous atrophy and iron deficiency may accelerate mucosal healing, villous recovery and remission.

Eligibility criteria: Inclusion Criteria:

* Patients free of mental illness, able to sign consent and \>18year
* Celiac disease confirmed by presence of serum celiac antibodies and villous atrophy on intestinal biopsy before starting gluten free diet (GFD)
* Intestinal villous atrophy on duodenal biopsy (performed within 1 month) showing villous atrophy
* Patient under GFD or starting GFD with strict compliance
* Hemoglobin level (Hb) \<12g/dL \& Hb\>8g/dL
* Well tolerated anemia
* Iron deficiency defined by: serum iron level \< 11 µmol/L, ferritinemia \< 20µg/L and/or transferrin saturation index \<0.2

Exclusion Criteria:

* Patient not able to sign, mental illness, pregnancy
* Complicated celiac disease: intestinal malignancies
* Severe anemia (Hb \<8g/dL) and/or poorly tolerated anemia requiring systematic iron IV supplementation or blood transfusion
* Serious severe disease having short-term prognostic implication
* Contraindication to intravenous iron infusion: known drug allergy
* Pregnant or breastfeeding women
* Participation in another interventional trial
* Patients treated by steroids, immunosuppressors or chemotherapy drugs

Primary outcomes:
measure: Total villous recovery
timeFrame: 12 months
Secondary outcomes:
measure: Atrophic gastritis
timeFrame: 12 months
measure: Partial recovery of intestinal villous atrophy
timeFrame: 12 months
measure: Iron deficiency
timeFrame: 12 months
measure: Anaemia
timeFrame: 12 months
measure: Intraepithelial lymphocytes
timeFrame: 12 months
measure: CD71 on epithelial cells
timeFrame: 12 months
measure: Body Mass Index
timeFrame: 12 months
measure: Serum folate level
timeFrame: 12 months
measure: Vitamin B12 level
timeFrame: 12 months
measure: Calcemia level
timeFrame: 12 months
measure: Albuminemia level
timeFrame: 12 months
measure: Corrected calcemia level
timeFrame: 12 months
measure: 25(OH)D3 vitamin level
timeFrame: 12 months
measure: Liver enzymes
timeFrame: 12 months
measure: Gluten free diet
timeFrame: 12 months
measure: Patient quality of life
timeFrame: 12 months
Other outcomes:
Locations:
city: Paris
country: France
facility: Hôpital Cochin
Study officials:
affiliation: Cochin, AP-HP, Paris
name: Georgia MALAMUT, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: