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| ID | Type | Description | Link |
|---|---|---|---|
| 2019-003125-21 | EudraCT Number | ||
| PHRCN-17-0647 | Other Grant/Funding Number | French Ministry of Health |
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Study suspended due to a new development; the project was no longer feasible.
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| Name | Class |
|---|---|
| Ministry of Health, France | OTHER_GOV |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Oral Iron + IV Ferinject | Experimental | 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. |
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| Oral Iron only | Active Comparator | Comparison group will not receive any intravenous treatment. Both experimental and comparison groups will receive an oral iron supplementation (100 mg/day). |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Ferinject | 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). |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Partial recovery of intestinal villous atrophy |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Georgia MALAMUT, MD, PhD | Cochin, AP-HP, Paris | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Hôpital Cochin | Paris | 75014 | France |
Individual participant data (IPD) that underlie results in publication could be shared. IPD detailed in the protocol of a planned metaanalysis could be shared
Two years after the last publication
Data sharing must be accepted by the sponsor and the PI based on a scientific project and scientific involvement of the PI team. Collaboration will be fostered.
Data sharing must respect the agreements made with funders.
Teams wishing obtain IPD must meet the sponsor and PI team to present scientific (and commercial) purpose, IPD needed, format of data transmission, and timeframe. Technical feasibility and financial support will be discussed before mandatory contractual agreement.
Processing of shared data must comply with European General Data Protection Regulation (GDPR).
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| ID | Term |
|---|---|
| D002446 | Celiac Disease |
| D000090463 | Iron Deficiencies |
| ID | Term |
|---|---|
| D008286 | Malabsorption Syndromes |
| D007410 | Intestinal Diseases |
| D005767 | Gastrointestinal Diseases |
| D004066 | Digestive System Diseases |
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| ID | Term |
|---|---|
| C522335 | ferric carboxymaltose |
| D007501 | Iron |
| ID | Term |
|---|---|
| D019216 | Metals, Heavy |
| D004602 | Elements |
| D007287 | Inorganic Chemicals |
| D028561 | Transition Elements |
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Phase IV, open, randomized, 2-arms parallel controlled trial with blinded assessment of end-point.
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Upper endoscopy with duodenal biopsy will be performed at most one month before randomization, and one month after the last infusion (experimental group) and between the 12th and the 13h month after randomization (control group). Histological analysis (villous recovery, primary endpoint) will be centrally performed by an expert pathologist blind to the group of treatment.
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| oral iron | Drug | All patients will receive an oral iron supplementation (100mg/day). |
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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 |
| 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 |
| 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 |
| Intraepithelial lymphocytes | Evolution of the count of intraepithelial lymphocytes assessed on initial and last control biopsy. | 12 months |
| CD71 on epithelial cells | Evolution of the expression of CD71 on epithelial cells studied on initial and last control biopsy | 12 months |
| Body Mass Index | Evolution of the patient's BMI during his participation at the study. | 12 months |
| Serum folate level | Serum folate level (µg/L) measured at visit V1, V3, V6, V10, V14. | 12 months |
| Vitamin B12 level | Level of vitamin B12 (pmol/L) measured at visit V1, V3, V6, V10, V14. | 12 months |
| Calcemia level | Level of calcemia (mmol/L) measured at visit V1, V3, V6, V10, V14. | 12 months |
| Albuminemia level | Level of albuminemia (g/L) measured at visit V1, V3, V6, V10, V14. | 12 months |
| Corrected calcemia level | Level of corrected calcemia (mmol/L) measured at visit V1, V3, V6, V10, V14. | 12 months |
| 25(OH)D3 vitamin level | Level of 25(OH)D3 vitamin measured at visit V1, V3, V6, V10, V14. | 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. | 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. | 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. | 12 months |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D019189 | Iron Metabolism Disorders |
| D008670 |
| Metals |