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

Leiden University Medical Center (LUMC)

Status and phase: Enrolling; Phase 4

Conditions: Iron Deficiency Anemia; Iron-deficiency; Inflammatory Bowel Diseases

Treatments: Drug: Ferrous fumarate; Drug: Ferric maltol; Drug: Intravenous iron

Study type: Interventional

Funder types: Other

Identifiers

NCT05456932

NL79105.058.22

2022-000894-16 (EudraCT Number)

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 90 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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)

Trial design

Primary purpose: Diagnostic

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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90 participants in 3 patient groups

Intravenous iron

Experimental group

Description:

Intravenous iron therapy

Treatment:

Drug: Intravenous iron

Ferric maltol

Experimental group

Description:

Treatment with oral ferric maltol

Treatment:

Drug: Ferric maltol

Ferrous fumarate

Experimental group

Description:

Treatment with oral ferrous fumarate

Treatment:

Drug: Ferrous fumarate