Effect of Intravenous Iron Supplementation on Celiac Disease Remission in Patients With Iron Deficiency and Intestinal Villous Atrophy: a Randomized Trial
试验速览
- 阶段
- 4 期
- 状态
- 终止
- 入组人数
- 1
- 试验地点
- 1
- 主要终点
- Total villous recovery
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
盲法说明
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.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
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).
干预措施: oral iron (Drug)
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.
干预措施: Ferinject (Drug)
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.
干预措施: oral iron (Drug)
结局指标
主要结局
Total villous recovery
时间窗: 12 months
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.
次要结局
- Atrophic gastritis(12 months)
- Partial recovery of intestinal villous atrophy(12 months)
- Iron deficiency(12 months)
- Anaemia(12 months)
- Intraepithelial lymphocytes(12 months)
- CD71 on epithelial cells(12 months)
- Body Mass Index(12 months)
- Serum folate level(12 months)
- Vitamin B12 level(12 months)
- Calcemia level(12 months)
- Albuminemia level(12 months)
- Corrected calcemia level(12 months)
- 25(OH)D3 vitamin level(12 months)
- Liver enzymes(12 months)
- Gluten free diet(12 months)
- Patient quality of life(12 months)