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

NCT05456932 | Unknown Phase 4 DMC

• 2 other identifiers: NL79105.058.222022-000894-16
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 5

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.

Conditions

Inflammatory Bowel Diseases; Iron-deficiency; Iron Deficiency Anemia

Keywords

IBD; Crohn's disease; Ulcerative colitis; Inflammatory Bowel Disease; Iron deficiency; Iron deficiency anemia

Outcome Measures

Primary Outcomes (3)

• 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%).

  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%).

  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%).

  Week 14

Secondary Outcomes (12)

• 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

Other Outcomes (1)

• Exploratory outcome: change in oxidative stress

  weeks 6, 14, and 24

Study Arms (3)

Intravenous iron

EXPERIMENTAL

Intravenous iron therapy

Drug: Intravenous iron

Ferric maltol

EXPERIMENTAL

Treatment with oral ferric maltol

Drug: Ferric maltol

Ferrous fumarate

EXPERIMENTAL

Treatment with oral ferrous fumarate

Drug: Ferrous fumarate

Interventions

Intravenous iron DRUG

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

Also known as: i.v. iron

Intravenous iron

Ferric maltol DRUG

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

Also known as: Feraccru

Ferric maltol

Ferrous fumarate DRUG

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

Also known as: ferrofumaraat

Ferrous fumarate

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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 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
• 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)

Sponsors & Collaborators

• Leiden University Medical Center: lead
• University Medical Center Groningen: collaborator
• Radboud University Medical Center: collaborator
• Maastricht University Medical Center: collaborator
• Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA): collaborator

Study Sites (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

Related Publications (1)

• 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.

  PMID: 38296290 DERIVED

MeSH Terms

Conditions

Inflammatory Bowel Diseases; Anemia, Iron-Deficiency; Crohn Disease; Colitis, Ulcerative; Iron Deficiencies

Interventions

ferric maltol; ferrous fumarate

Condition Hierarchy (Ancestors)

Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases; Anemia, Hypochromic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Iron Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Colitis; Colonic Diseases

Study Officials

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

  LUMC

  PRINCIPAL INVESTIGATOR

Central Study Contacts

R. Loveikyte, MD

CONTACT

00315297902; patientenibd@lumc.nl

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: May 10, 2022
• First Posted: July 13, 2022
• Study Start: August 19, 2022
• Primary Completion: August 31, 2023
• Study Completion: August 31, 2023
• Last Updated: March 31, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share

Locations

NL (5)