To evaluate if hepcidin levels can predict response to iron therapy with either ferrous fumarate, ferric maltol, and intravenous iron in patients with IBD.
ID
Source
Brief title
Condition
- Gastrointestinal inflammatory conditions
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Whether hepcidin levels at baseline can predict response to iron therapy with
either ferrous fumarate, ferric maltol, or intravenous iron (main parameters:
hepcidin at baseline, binary response (yes / no) to iron therapy. The response
to iron therapy is defined as an increase >1.2 mmol/l in hemoglobin or
hemoglobin normalization at week 14 for patients with iron deficiency anemia;
or an increase in ferritin >100 µg/l) and transferrin saturation >20% at week
14 for patients with iron deficiency without anemia)
Secondary outcome
- Changes in quality of life (SF-36)
- Changes in IBD disease activity (mHI)
- Changes in (work) activity impairment (WPAI)
- Changes in hypoxie- or inflammatiion-associated biomarkers, oxidative stress,
microbiome
- Hypophosphatemia and other side effects
Background 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. Multiple factors regulate hepcidin
synthesis: inflammation and iron overload upregulate hepcidin levels, while
increased erythropoiesis, iron deficiency, and hypoxia downregulate hepcidin.
Elevated hepcidin is associated with oral iron malabsorption in IBD. On the
other hand, animal studies showed that iron deficiency could downregulate
hepcidin even in inflammatory states, which leads to the question: which IBD
patients should be treated with oral iron, and which patients should be treated
with intravenous iron? Can we predict the response to iron therapy in patients
with IBD?
Study objective
To evaluate if hepcidin levels can predict response to iron therapy with either
ferrous fumarate, ferric maltol, and intravenous iron in patients with IBD.
Study design
Multicenter, prospective, and an exploratory study.
Intervention
A. Ferrous fumarate 2dd 100mg p.o. for 12 weeks
B. Ferric maltol 2dd 30mg p.o. for 12 weeks
C. Intravenous iron: dosage based on instructions on the national formulary
'Farmacotherapeutisch Kompas'
Study burden and risks
The risk for study subjects is negligible because patients do not run
additional risk compared to standard care. Even outside the context of the
study, patients would have to get their blood and stool samples tested as part
of their IBD-care; in addition, they would need iron therapy for iron
deficiency. Because patients need iron therapy, there is a risk of side effects
or allergic reactions. These side effects are generally mild and reversible
(e.g., constipation, tarry stool, or abdominal pain). Blood tests for study
measurements will be done at the same time as tests for the standard care;
hence, patients will not have an increased risk related to venipuncture. During
24 weeks, patients have to get tested four times, which yields an additional
40ml of blood for each blood withdrawal; however, the total amount of withdrawn
blood volume is negligible and it will not increase patient's risk. In
addition, delivering stool samples is not invasive and serves no risks to
patients. Last but not least, patients will have to fill out three
questionnaires over the course of the study. The questionnaires are short and
not intrusive, it will take about 60 minutes to fill out all study
questionnaires.
It is known that iron deficiency and anemia are frequent and recurrent problems
in patients with IBD. Given that this is a study with a negligible risk, we
think it is justified to perform this study. The results may lead to
personalized iron therapy in patients with IBD.
Albinusdreef 2
Leiden 2300RC
NL
Albinusdreef 2
Leiden 2300RC
NL
Listed location countries
Age
Inclusion criteria
- Established IBD diagnosis (Crohn's disease, ulcerative colitis,
IBD-unclassified) - Adults (>=18 years of age) - Active IBD (defined as
biochemical activity CRP >5 mg/L and/or FCP >150 mg/kg or as any endoscopic or
radiologic disease activity) - 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 (COPD) - 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 eGFR
<30 ml/min/1.73m2) - Folic acid or vitamin B12 deficiency in combination with a
macrocytic anemia (Mean Corpuscular Volume >100 fL + Hb <7.5 mmol/L for females
or Hb <8.5 mmol/L for males) - 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)
Design
Recruitment
Medical products/devices used
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
Followed up by the following (possibly more current) registration
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Other (possibly less up-to-date) registrations in this register
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In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2022-000894-16-NL |
| CCMO | NL79105.058.22 |