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

NCT ID: NCT05456932

Last Updated: 2023-03-31

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE4
• Total Enrollment: 90 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-08-19
• Study Completion Date: 2023-08-31

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.

Conditions

Inflammatory Bowel Diseases; Iron-deficiency; Iron Deficiency Anemia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: NONE

Study Groups

Intravenous iron

Intravenous iron therapy

Group Type: EXPERIMENTAL

Intravenous iron

Intervention Type: DRUG

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

Ferric maltol

Treatment with oral ferric maltol

Group Type: EXPERIMENTAL

Ferric maltol

Intervention Type: DRUG

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

Ferrous fumarate

Treatment with oral ferrous fumarate

Group Type: EXPERIMENTAL

Ferrous fumarate

Intervention Type: DRUG

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

Interventions

Intravenous iron

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

Intervention Type: DRUG

Ferric maltol

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

Intervention Type: DRUG

Ferrous fumarate

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

Intervention Type: DRUG

Other Intervention Names

i.v. iron; Feraccru; ferrofumaraat

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)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Medical Center Groningen

OTHER

Sponsor Role: collaborator

Radboud University Medical Center

OTHER

Sponsor Role: collaborator

Maastricht University Medical Center

OTHER

Sponsor Role: collaborator

Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

OTHER

Sponsor Role: collaborator

Leiden University Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Andrea E. van der Meulen - de Jong, MD, PhD

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

A.E. van der Meulen - de Jong, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

LUMC

Locations

Amsterdam University Medical Center

Amsterdam, , Netherlands

Site Status: RECRUITING

University Medical Center Groningen

Groningen, , Netherlands

Site Status: RECRUITING

Leiden University Medical Center (LUMC)

Leiden, , Netherlands

Site Status: RECRUITING

Maastricht University Medical Center+

Maastricht, , Netherlands

Site Status: RECRUITING

Radboud University Medical Center

Nijmegen, , Netherlands

Site Status: RECRUITING

Countries

Netherlands

Central Contacts

R. Loveikyte, MD

Role: CONTACT

patientenibd@lumc.nl

00315297902

Facility Contacts

R. Loveikyte, MD

Role: primary

R. Loveikyte, MD

Role: primary

R. Loveikyte, MD

Role: primary

R. Loveikyte, MD

Role: primary

R. Loveikyte, MD

Role: primary

References

Loveikyte R, Duijvestein M, Mujagic Z, Goetgebuer RL, Dijkstra G, van der Meulen-de Jong AE. Predicting response to iron supplementation in patients with active inflammatory bowel disease (PRIme): a randomised trial protocol. BMJ Open. 2024 Jan 30;14(1):e077511. doi: 10.1136/bmjopen-2023-077511.

Reference Type: DERIVED

PMID: 38296290 (View on PubMed)

Other Identifiers

2022-000894-16

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

NL79105.058.22

Identifier Type: -

Identifier Source: org_study_id