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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
SINGLE
Enrollment
204
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).
All patients will receive an oral iron supplementation (100mg/day).
Hôpital Cochin
Paris, France
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.
Time frame: 12 months
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)
Time frame: 12 months
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.
Time frame: 12 months
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.
Time frame: 12 months
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.
Time frame: 12 months
Intraepithelial lymphocytes
Evolution of the count of intraepithelial lymphocytes assessed on initial and last control biopsy.
Time frame: 12 months
CD71 on epithelial cells
Evolution of the expression of CD71 on epithelial cells studied on initial and last control biopsy
Time frame: 12 months
Body Mass Index
Evolution of the patient's BMI during his participation at the study.
Time frame: 12 months
Serum folate level
Serum folate level (µg/L) measured at visit V1, V3, V6, V10, V14.
Time frame: 12 months
Vitamin B12 level
Level of vitamin B12 (pmol/L) measured at visit V1, V3, V6, V10, V14.
Time frame: 12 months
Calcemia level
Level of calcemia (mmol/L) measured at visit V1, V3, V6, V10, V14.
Time frame: 12 months
Albuminemia level
Level of albuminemia (g/L) measured at visit V1, V3, V6, V10, V14.
Time frame: 12 months
Corrected calcemia level
Level of corrected calcemia (mmol/L) measured at visit V1, V3, V6, V10, V14.
Time frame: 12 months
25(OH)D3 vitamin level
Level of 25(OH)D3 vitamin measured at visit V1, V3, V6, V10, V14.
Time frame: 12 months
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.
Time frame: 12 months
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.
Time frame: 12 months
Patient quality of life
French Celiac disease questionnaire assessed at V1 and V14 about the evolution of the quality of life for the patient.
Time frame: 12 months
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