Iron Deficiency
Conditions
Brief summary
Iron deficiency is common in cardiorespiratory diseases and appears to contribute to a worse outcome. This human physiology study will examine the extent to which human skeletal muscle metabolism and exercise physiology are impaired by iron deficiency.
Detailed description
This is a prospective double-blind randomised controlled study of the effect of endogenous iron status on skeletal muscle metabolism and exercise physiology. 32 healthy volunteers will take part, half of whom will be iron-deficient. The study involves a screening visit and two half-day visits during which assessments are performed. 50% of each group will be randomised to receive iron-repletion with ferric carboxymaltose at the end of the first experimental visit before returning to repeat identical assessments around one week later. This approach will make it possible to explore whether baseline differences in skeletal muscle metabolism are explained by differences in iron status per se, whilst controlling for any learning effect during participation in the study.
Interventions
DRUGFerric carboxymaltose
Infusion of 15 mg/kg (up to maximum 1000 mg) ferric carboxymaltose in 250 mL 0.9% sodium chloride
Infusion of 250 mL 0.9% sodium chloride
Sponsors
British Heart Foundation
National Institute for Health Research, United Kingdom
University of Oxford
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Willing and able to give informed consent for participation in the study * Men and women aged 18 years or older and generally in good health * For iron-deficient volunteers: ferritin ≤ 15 microg/L and transferrin saturation \< 16% * For iron-replete volunteers: ferritin ≥ 20 microg/L and transferrin saturation ≥ 20%
Exclusion criteria
* Haemoglobin \< 8.0 g/dL * Haemoglobinopathy * Iron overload, defined as ferritin \> 300 microg/L * Hypoxaemia (SpO2 \< 94%) or significant co-morbidity that may affect haematinics, metabolic or ventilatory responses * Iron supplementation or blood transfusion within the previous 6 weeks * Pregnancy or breast feeding * Inability to exercise isolated calf muscle using a pedal or on a bicycle ergometer * Contraindication to magnetic resonance spectroscopy exposure such as metallic implant * Contraindication to receiving intravenous ferric carboxymaltose
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phosphocreatine depletion during small muscle mass exercise | 36 minute long graded exercise test; performed at baseline and follow-up visits (approximately a week apart) | Degree of phosphocreatine depletion during graded exercise of calf muscle assessed using magnetic resonance spectroscopy |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cardiopulmonary exercise test performance | Hour long graded exercise test; performed at baseline and follow-up visits (approximately a week apart) | Blood lactate and cardiorespiratory parameters during moderate large skeletal muscle mass exercise, assessed with cardiopulmonary exercise testing |
| Muscle biopsy findings | Immediately before and immediately after hour long cardiopulmonary exercise test, performed at baseline and follow-up visits (approximately a week apart) | Skeletal muscle characteristics, assessed by minimally-invasive muscle biopsy (not a compulsory part of the protocol) |
| Participant reported symptoms | At study screening visit compared to four weeks following infusion of iron or placebo | Measures of fatigue, restless-legs syndrome and well-being assessed by self-reported questionnaires |
Countries
United Kingdom
Outcome results
None listed