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

NCT ID: NCT05114278

Last Updated: 2022-01-19

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 204 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-02-15
• Study Completion Date: 2026-04-15

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.

Conditions

Celiac Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Oral Iron + IV 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.

Group Type: EXPERIMENTAL

Ferinject

Intervention Type: DRUG

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

Intervention Type: DRUG

All patients will receive an oral iron supplementation (100mg/day).

Oral Iron only

Comparison group will not receive any intravenous treatment. Both experimental and comparison groups will receive an oral iron supplementation (100 mg/day).

Group Type: ACTIVE_COMPARATOR

oral iron

Intervention Type: DRUG

All patients will receive an oral iron supplementation (100mg/day).

Interventions

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).

Intervention Type: DRUG

oral iron

All patients will receive an oral iron supplementation (100mg/day).

Intervention Type: DRUG

Other Intervention Names

Experimental arm; Control arm

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Ministry of Health, France

OTHER_GOV

Sponsor Role: collaborator

Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Georgia MALAMUT, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Cochin, AP-HP, Paris

Locations

Hôpital Cochin

Paris, , France

Countries

France

Central Contacts

Karine GOUDE-ORY, MSc

Role: CONTACT

karine.goude@aphp.fr

+33144841722

Sabrina BOUDIF, MSc

Role: CONTACT

sabrina.boudif@aphp.fr

+33156095976

Facility Contacts

Georgia MALAMUT, MD, PhD

Role: primary

Other Identifiers

2019-003125-21

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

PHRCN-17-0647

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

P170915J

Identifier Type: -

Identifier Source: org_study_id