Iron Status and Human Metabolism

Study Overview
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Brief Summary
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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
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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.

Official Title
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Effects of Endogenous Iron Status and Intravenous Iron on Human Skeletal Muscle Metabolism at Rest and During Exercise

Conditions
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Iron Deficiency

Intervention / Treatment
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* Drug: Ferric carboxymaltose
* Drug: Sodium chloride (placebo)


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Iron-deficient, given placebo<br>Iron-deficient participants given an infusion of sodium chloride at conclusion of baseline experimental visit | Drug: Sodium chloride (placebo)<br>* Infusion of 250 mL 0.9% sodium chloride<br>* Other names: Normal saline;|
| Active Comparator: Iron-deficient, given iron<br>Iron-deficient participants given an infusion of ferric carboxymaltose at conclusion of baseline experimental visit | Drug: Ferric carboxymaltose<br>* Infusion of 15 mg/kg (up to maximum 1000 mg) ferric carboxymaltose in 250 mL 0.9% sodium chloride<br>* Other names: Ferinject;|
| Placebo Comparator: Iron-replete, given placebo<br>Iron-replete participants given an infusion of sodium chloride at conclusion of baseline experimental visit | Drug: Sodium chloride (placebo)<br>* Infusion of 250 mL 0.9% sodium chloride<br>* Other names: Normal saline;|
| Active Comparator: Iron-replete, given iron<br>Iron-deficient participants given an infusion of ferric carboxymaltose at conclusion of baseline experimental visit | Drug: Ferric carboxymaltose<br>* Infusion of 15 mg/kg (up to maximum 1000 mg) ferric carboxymaltose in 250 mL 0.9% sodium chloride<br>* Other names: Ferinject;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phosphocreatine depletion during small muscle mass exercise | Degree of phosphocreatine depletion during graded exercise of calf muscle assessed using magnetic resonance spectroscopy | 36 minute long graded exercise test; performed at baseline and follow-up visits (approximately a week apart) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cardiopulmonary exercise test performance | Blood lactate and cardiorespiratory parameters during moderate large skeletal muscle mass exercise, assessed with cardiopulmonary exercise testing | Hour long graded exercise test; performed at baseline and follow-up visits (approximately a week apart) | 
| Muscle biopsy findings | Skeletal muscle characteristics, assessed by minimally-invasive muscle biopsy (not a compulsory part of the protocol) | Immediately before and immediately after hour long cardiopulmonary exercise test, performed at baseline and follow-up visits (approximately a week apart) | 
| Participant reported symptoms | Measures of fatigue, restless-legs syndrome and well-being assessed by self-reported questionnaires | At study screening visit compared to four weeks following infusion of iron or placebo |