Clinical trial NCT01519830: Iron Substitution in Blood Donors
Official title: Significance of Iron Deficiency in Transfusion Medicine: Effects of Iron Substitution on Fatigue Und General Well Being in Healthy Blood Donors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Fatigue
Keywords: Anemia, Iron-Deficiency
Blood Donors
Lead sponsor: Insel Gruppe AG, University Hospital Bern
Sponsor class: OTHER
Collaborators: name: Blutspendedienst SRK Bern AG, 3008 Bern, Switzerland
name: University of Bern
name: Humanitäre Stiftung des Schweizerischen Roten Kreuzes, 3011 Bern, Switzerland
First posted: 2012-01-27
Enrollment: 405
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Depletion of iron stores is frequently observed in regular blood donors, but effects of iron deficiency on general health is not well studied. Recent studies in women suffering of fatigue suggest iron deficiency without concomitant anemia as a common cause of these complaints. Provided the same is true in healthy subjects, substitution of intravenous iron might result in an improvement of general well being in iron depleted blood donors.

Healthy regular blood donors will be screened for low storage iron. Qualifying subjects will be invited to participate in a randomized, placebo-controlled trial with substitution of intravenous iron or placebo (saline solution). Differences in subjectively felt fatigue and other factors of general health and well being will be assessed. If an improvement of such factors can be shown after iron replacement, relevant concerns about artificially lowering iron stores by repeated phlebotomies will arise and changes of monitoring and substitution policies in blood banking might have to be discussed.

Detailed description: Background

Chronic iron deficiency causes anemia with impairment of physical and mental capacity. Since iron plays an essential role in many enzymes apart from oxygen carriage, iron deficiency was proposed as an independent factor impairing wellbeing also without anemia. Symptoms like fatigue, asthenia, physical weakness, mental impairment and many others have been associated with iron deficiency. Recent clinical trials with iron substitution in iron deficient women suffering of general fatigue support this hypothesis, but data are still conflicting and debated.

Low body iron stores are frequently observed in blood donors. Repeated phlebotomies may induce or aggravate severe iron deficiency. Astonishingly, little is known about the long term effects of reduced iron stores on general health of regular blood donors. Serious health impairment cannot be excluded conclusively. Since many symptoms associated with iron deficiency are subtle, they might be missed by otherwise healthy subjects.

Blood donors with borderline or decreased iron stores (i.e. serum ferritin below 50 microg/l) will be invited to participate in a randomized, placebo-controlled intervention study comparing intravenous iron carboxymaltose and a physiological saline solution (placebo). Subjectively felt fatigue, measured on a numeric rating scale from 1 to 10 as the major end point will be assessed before and six months after application of the study drug. As additional factors, various aspects of general wellbeing will be assessed using four psychometric questionnaires. Statistical analysis will compare the results before and after application of the study drug and the results of the two study arms.

Objective

1. Assessment of severity of iron deficiency in a large group of blood donors.
2. Demonstration of an improvement of fatigue after substitution of iron compared with placebo in iron deficient blood donors
3. Detection of improved general wellbeing in otherwise healthy blood donors after substitution of intravenous iron
4. Assessment of tolerability of intravenous iron in healthy blood donors

Methods

Randomized, placebo controlled interventional trial comparing the effect of intravenous iron or placebo on fatigue and various other factors of general wellbeing. Endpoints assessed on a numeric rating scale from 1 to 10 and four psychometric questionnaires.

Eligibility criteria: Inclusion Criteria:

* Serum-Ferritin 50 microg/l
* Eligibility for blood donation
* At least one prior blood donation

Exclusion Criteria

* Anemia
* Known intolerability of intravenous iron
* History of anaphylactic reactions
* Active systemic infections
* Signs of chronic bleeding
* Known iron overload
* Lactation
* Pregnancy
* Any disease associated with increased fatigue
* Medication associated with increased fatigue

Primary outcomes:
measure: Difference of fatigue on a 10 point numeric scale after intravenous substitution of iron or placebo
timeFrame: 6 weeks
Secondary outcomes:
measure: Change of fatigue after intravenous substitution of iron
timeFrame: 6 weeks
measure: Improvement of general wellbeing
timeFrame: 6 weeks
measure: Number of patients with adverse events of different grades
timeFrame: 6 weeks
Other outcomes:
Locations:
city: Bern
country: Switzerland
facility: Department of Hematology, Bern University Hospital
Study officials:
affiliation: Department of Hematology, Bern University Hospital, Switzerland
name: Peter Keller, MD
role: STUDY_CHAIR
affiliation: Department of Hematology, Bern University Hospital, Switzerland
name: Bernhard Lämmle, MD, Prof.
role: STUDY_CHAIR
affiliation: Blutspendedienst SRK Bern AG, Bern, Switzerland
name: Stefano Fontana, MD
role: STUDY_CHAIR
affiliation: Institut für Sozial- und Präventivmedizin, Universität Bern, Switzerland
name: Peter Jüni, MD, Prof.
role: STUDY_CHAIR
affiliation: Kompetenzbereich für Psychosomatische Medizin, University Hospital Bern
name: Roland von Känel, MD, Prof.
role: STUDY_CHAIR
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