Effect of Intravenous Iron Supplementation on Celiac Disease Remission (IRONCEL)

Celiac Disease Clinical Trial

— IRONCEL  

Official title:

Effect of Intravenous Iron Supplementation on Celiac Disease Remission in Patients With Iron Deficiency and Intestinal Villous Atrophy: a Randomized Trial

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05114278
• Other study ID #: P170915J
• Secondary ID: 2019-003125-21PH
• Status: Not yet recruiting
• Phase: Phase 4
• Start date: February 15, 2022
• Est. completion date: April 15, 2026

Study information

• Verified date: January 2022
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: Karine GOUDE-ORY, MSc
• Phone: +33144841722
• Email: karine.goude[@]aphp.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 204
• Est. completion date: April 15, 2026
• Est. primary completion date: April 15, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Celiac Disease

Intervention

Drug:
• Ferinject
Experimental group will receive intravenous iron infusion (Ferinject©: 15 mg/kg in NaCl solution IV) at randomization, 2weeks after randomization, 4weeks after randomization, and then every month for a total of one year. Comparison group will not receive any intravenous treatment. Both experimental and comparison groups will receive an oral iron supplementation (100 mg/day).
• oral iron
All patients will receive an oral iron supplementation (100mg/day).

Locations

Country	Name	City	State
France	Hôpital Cochin	Paris

Sponsors (2)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris	Ministry of Health, France

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Total villous recovery	The primary endpoint is the proportion of patients with total villous recovery (total remission) on the last duodenal biopsies. 6 formalin and 2 frozen duodenal biopsies will be performed. Intestinal mucosal assessment will be performed by a centralized histological analysis according to the Marsh classification. Readers will be blind to the treatment received.	12 months
Secondary	Atrophic gastritis	Proportion of patients with atrophic gastritis at V0 and at V14 biopsies (2 in the antrum, 1 in the angulus and 2 in the fundus)	12 months
Secondary	Partial recovery of intestinal villous atrophy	Proportion of patients with partial recovery of intestinal villous atrophy on the last control duodenal biopsies according to Marsh classification (centralized histological analysis). Six formalin and two frozen duodenal biopsies will be performed.	12 months
Secondary	Iron deficiency	Proportion of patients correcting iron deficiency. Iron parameters (serum iron level (µmol/L), ferritinemia (µg/L), transferrin saturation index) will be assessed at visit V1, V3, V6, V10, V14; correction of iron deficiency is defined by serum iron level > 20 µg/L and transferrin saturation index =0.20.	12 months
Secondary	Anaemia	Proportion of patients correcting anaemia during the 12 months participation. Hemoglobin (Hb) level (g/d) will be measured at visit V1, V3, V6, V10, V14. Correction of anaemia is defined by Hb=12g/L in woman and Hb=13g/dL in man.	12 months
Secondary	Intraepithelial lymphocytes	Evolution of the count of intraepithelial lymphocytes assessed on initial and last control biopsy.	12 months
Secondary	CD71 on epithelial cells	Evolution of the expression of CD71 on epithelial cells studied on initial and last control biopsy	12 months
Secondary	Body Mass Index	Evolution of the patient's BMI during his participation at the study.	12 months
Secondary	Serum folate level	Serum folate level (µg/L) measured at visit V1, V3, V6, V10, V14.	12 months
Secondary	Vitamin B12 level	Level of vitamin B12 (pmol/L) measured at visit V1, V3, V6, V10, V14.	12 months
Secondary	Calcemia level	Level of calcemia (mmol/L) measured at visit V1, V3, V6, V10, V14.	12 months
Secondary	Albuminemia level	Level of albuminemia (g/L) measured at visit V1, V3, V6, V10, V14.	12 months
Secondary	Corrected calcemia level	Level of corrected calcemia (mmol/L) measured at visit V1, V3, V6, V10, V14.	12 months
Secondary	25(OH)D3 vitamin level	Level of 25(OH)D3 vitamin measured at visit V1, V3, V6, V10, V14.	12 months
Secondary	Liver enzymes	Evolution of serum levels of liver enzymes (AST, ALT, AP, gGT, Total Bilirubin), glycemia, T4, TSH measured at visit V1, V3, V6, V10, V14.	12 months
Secondary	Gluten free diet	Observance of gluten free diet will be assessed by (i) dietitian assessment of gluten free consumption (g/day and proportion of patients in high (0 g/day), medium (0-50 mg/day), low (>50 mg/day) observance), (ii) measurement of serum celiac antibodies (anti-tTG IgA and anti-deamidated gliadin IgG) and (iii) proportion of patients having gluten immunogenic peptides excretion detected in urine at visit V1, V3, V6,V10, V14.	12 months
Secondary	Patient quality of life	French Celiac disease questionnaire assessed at V1 and V14 about the evolution of the quality of life for the patient.	12 months