Clinical trial NCT05456932: Predicting Response to Iron Supplementation in Patients With Active Inflammatory Bowel Disease
Official title: Predicting Response to Iron Supplementation in Patients With Active Inflammatory Bowel Disease
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Inflammatory Bowel Diseases
Iron-deficiency
Iron Deficiency Anemia
Keywords: IBD
Crohn's disease
Ulcerative colitis
Inflammatory Bowel Disease
Iron deficiency
Iron deficiency anemia
Lead sponsor: Leiden University Medical Center
Sponsor class: OTHER
Collaborators: name: University Medical Center Groningen
name: Radboud University Medical Center
name: Maastricht University Medical Center
name: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
First posted: 2022-07-13
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: DIAGNOSTIC

Brief summary: 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.

Detailed 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.

Eligibility criteria: 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)

Primary outcomes:
measure: The discriminative capacity of hepcidin at baseline to differentiate between response and non-response to iron therapy with oral ferrous fumarate
timeFrame: Week 14
measure: The discriminative capacity of hepcidin at baseline to differentiate between response and non-response to iron therapy with oral ferric maltol
timeFrame: Week 14
measure: The discriminative capacity of hepcidin at baseline to differentiate between response and non-response to intravenous iron therapy
timeFrame: Week 14
Secondary outcomes:
measure: Change in hepcidin
timeFrame: weeks 6, 14, and 24
measure: Change in soluble Transferrin Receptor (sTfR)
timeFrame: weeks 6, 14, and 24
measure: Change in interleukin 6 (IL-6)
timeFrame: weeks 6, 14, and 24
measure: Normalization of iron stores
timeFrame: weeks 6, 14, and 24
measure: Correlation between response to iron therapy and disease activity
timeFrame: week 14
measure: Incidence of hypophosphatemia during iron therapy
timeFrame: weeks 6, 14, and 24
measure: Adverse events during iron therapy
timeFrame: weeks 6, 14, and 24
measure: Change in clinical disease activity
timeFrame: weeks 14 and 24
measure: Change in quality of life
timeFrame: weeks 14 and 24
measure: Change in activity and productivity
timeFrame: weeks 14 and 24
measure: Hematologic response during iron therapy
timeFrame: weeks 14 and 24
measure: Hemoglobin increase (>0.6 mmol/L) during iron therapy
timeFrame: weeks 6 and 14
Other outcomes:
measure: Exploratory outcome: change in oxidative stress
timeFrame: weeks 6, 14, and 24
Locations:
city: Amsterdam
country: Netherlands
facility: Amsterdam University Medical Center
city: Groningen
country: Netherlands
facility: University Medical Center Groningen
city: Leiden
country: Netherlands
facility: Leiden University Medical Center (LUMC)
city: Maastricht
country: Netherlands
facility: Maastricht University Medical Center+
city: Nijmegen
country: Netherlands
facility: Radboud University Medical Center
Study officials:
affiliation: LUMC
name: A.E. van der Meulen - de Jong, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: