Predicting Response to Iron Supplementation in Patients With Active Inflammatory Bowel Disease
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 发起方
- 入组人数
- 90
- 试验地点
- 5
- 主要终点
- The discriminative capacity of hepcidin at baseline to differentiate between response and non-response to iron therapy with oral ferrous fumarate
研究概览
简要总结
Iron deficiency anemia is the most common systemic manifestation of Inflammatory Bowel Diseases (IBD)-Crohn's disease and ulcerative colitis. Iron deficiency with or without anemia poses a diagnostic and therapeutic challenge due to chronic gastrointestinal blood loss and the inflammatory nature of IBD. Recent illumination of iron metabolism has brought attention to the systemic iron regulator-hepcidin, a peptide hormone that regulates intestinal iron absorption and systemic iron availability. Elevated hepcidin is associated with oral iron malabsorption in IBD. This study aims to evaluate whether hepcidin concentration at baseline can predict response to oral and intravenous iron therapy in patients with IBD and concomitant iron deficiency with or without anemia.
详细描述
The PRIme is a multicenter and randomized study that aims to evaluate the capacity of hepcidin at baseline to predict response to oral or intravenous iron therapy in patients with active IBD. Study participants will be randomized and allocated (open-label) to one of the three study arms: intravenous iron therapy, therapy with oral ferrous fumarate, or therapy with oral ferric maltol.
During the study, biochemical indices such as hemoglobin, iron status, hepcidin and related cytokines will be measured at week 6, 14, and 24 after the start of the therapy. In addition, the study will evaluate changes in oxidative stress, quality of live, and productivity.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Diagnostic
- 盲法
- None
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
- •Established IBD diagnosis (Crohn's disease, ulcerative colitis, IBD-unclassified)
- •Adults (≥18 years of age)
- •Active IBD (defined as any endoscopic, radiologic or biochemical disease activity [fecal calprotectin >150 mg/kg or C-reactive protein >5 mg/l])
- •Iron deficiency anemia (defined as ferritin <100 ug/l and hemoglobin <7.5 mmol/l for females or <8.5 mmol/l for males) or iron deficiency (defined as ferritin <100 ug/l and transferrin saturation <20%)
- •Documented informed consent
排除标准
- •Blood transfusion or therapy with oral and/or intravenous iron in the past eight weeks
- •Documented intolerance to oral or intravenous iron
- •Severe anemia (defined as hemoglobin <6.2 mmol/l for females and males)
- •Documented history of liver cirrhosis, heart failure, hemoglobinopathies, autoimmune hemolytic anemia, myelodysplastic syndrome, or chronic obstructive pulmonary disease
- •Documented history of recent treatment for a malignancy (excluding dermatological malignancies such as basal cell carcinoma or squamous cell carcinoma). Patients can be included if the treatment for malignancy has been finalized ≥6 months before the inclusion date.
- •Documented history of bariatric surgery or gastric/duodenal resections due to benign or malignant pathologies
- •End-stage renal disease (impaired renal function, defined as estimated Glomerular Filtration Rate (eGFR) <30 ml/min/1.73m2)
- •Folic acid deficiency
- •Vitamin B12 deficiency
- •Documented pregnancy or breastfeeding at the time of inclusion
- •Documented major operation (e.g., laparotomy) less than six weeks before inclusion
- •Unable to give informed consent due to inability to understand Dutch language or incapacitation (e.g., due to cognitive/psychological conditions or hospitalization in Intensive Care)
研究组 & 干预措施
Intravenous iron
Intravenous iron therapy
干预措施: Intravenous iron (Drug)
Ferric maltol
Treatment with oral ferric maltol
干预措施: Ferric maltol (Drug)
Ferrous fumarate
Treatment with oral ferrous fumarate
干预措施: Ferrous fumarate (Drug)
结局指标
主要结局
The discriminative capacity of hepcidin at baseline to differentiate between response and non-response to iron therapy with oral ferrous fumarate
时间窗: Week 14
Hepcidin concentration will be measured in blood at baseline. Receiver Operating Characteristic (ROC) curve with associated Area Under the Curve (AUC) will be used to evaluate the discriminative ability of hepcidin concentration at baseline to differentiate between response and non-response to iron therapy with ferrous fumarate. Response to iron therapy will be evaluated at week 14 and will be defined as hemoglobin normalization (or \>1.2 mmol/L increase) for patients with iron-deficiency anemia; for patients with non-anemic iron deficiency the response will be defined as normalization of iron stores (i.e., ferritin \>100 ug/L and transferrin saturation \>20%).
The discriminative capacity of hepcidin at baseline to differentiate between response and non-response to iron therapy with oral ferric maltol
时间窗: Week 14
Hepcidin concentration will be measured in blood at baseline. Receiver Operating Characteristic (ROC) curve with associated Area Under the Curve (AUC) will be used to evaluate the discriminative ability of hepcidin concentration at baseline to differentiate between response and non-response to iron therapy with ferric maltol. Response to iron therapy will be evaluated at week 14 and will be defined as hemoglobin normalization (or \>1.2 mmol/L increase) for patients with iron-deficiency anemia; for patients with non-anemic iron deficiency the response will be defined as normalization of iron stores (i.e., ferritin \>100 ug/L and transferrin saturation \>20%).
The discriminative capacity of hepcidin at baseline to differentiate between response and non-response to intravenous iron therapy
时间窗: Week 14
Hepcidin concentration will be measured in blood at baseline. Receiver Operating Characteristic (ROC) curve with associated Area Under the Curve (AUC) will be used to evaluate the discriminative ability of hepcidin concentration at baseline to differentiate between response and non-response to intravenous iron therapy. Response to iron therapy will be evaluated at week 14 and will be defined as hemoglobin normalization (or \>1.2 mmol/L increase) for patients with iron-deficiency anemia; for patients with non-anemic iron deficiency the response will be defined as normalization of iron stores (i.e., ferritin \>100 ug/L and transferrin saturation \>20%).
次要结局
- Change in hepcidin(weeks 6, 14, and 24)
- Change in soluble Transferrin Receptor (sTfR)(weeks 6, 14, and 24)
- Change in interleukin 6 (IL-6)(weeks 6, 14, and 24)
- Normalization of iron stores(weeks 6, 14, and 24)
- Correlation between response to iron therapy and disease activity(week 14)
- Incidence of hypophosphatemia during iron therapy(weeks 6, 14, and 24)
- Adverse events during iron therapy(weeks 6, 14, and 24)
- Change in clinical disease activity(weeks 14 and 24)
- Change in quality of life(weeks 14 and 24)
- Change in activity and productivity(weeks 14 and 24)
- Hematologic response during iron therapy(weeks 14 and 24)
- Hemoglobin increase (>0.6 mmol/L) during iron therapy(weeks 6 and 14)
研究者
Andrea E. van der Meulen - de Jong, MD, PhD
Principal Investigator
Leiden University Medical Center