Predicting Response to Iron Supplementation in Patients With Active Inflammatory Bowel Disease

Leiden University Medical Center90 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

DIAGNOSTIC

Masking

NONE

Enrollment

Conditions

Inflammatory Bowel Diseases

Interventions

Intravenous ironDRUG

Included participants will receive intravenous iron therapy, the dosage will be based on national pharmaceutical formulary.

Ferric maltolDRUG

Included participants will receive oral iron therapy with ferric maltol (twice a day 30mg for 12 weeks)

Ferrous fumarateDRUG

Included participants will receive oral iron therapy with ferrous fumarate (twice a day 100mg for 12 weeks)

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * 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 Exclusion Criteria: * 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)

Locations (5)

Amsterdam University Medical Center

Amsterdam, Netherlands

RECRUITING

University Medical Center Groningen

Groningen, Netherlands

RECRUITING

Leiden University Medical Center (LUMC)

Leiden, Netherlands

RECRUITING

Maastricht University Medical Center+

Maastricht, Netherlands

RECRUITING

Radboud University Medical Center

Nijmegen, Netherlands

RECRUITING

Outcomes

Primary Outcomes

The discriminative capacity of hepcidin at baseline to differentiate between response and non-response to iron therapy with oral ferrous fumarate

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%).

Time frame: Week 14

The discriminative capacity of hepcidin at baseline to differentiate between response and non-response to iron therapy with oral ferric maltol

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%).

Time frame: Week 14

The discriminative capacity of hepcidin at baseline to differentiate between response and non-response to intravenous iron therapy

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%).

Time frame: Week 14