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Iron Status and Human Metabolism

Not Applicable
Completed
Conditions
Iron Deficiency
Interventions
Registration Number
NCT02308449
Lead Sponsor
University of Oxford
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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
29
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Iron-replete, given placeboSodium chloride (placebo)Iron-replete participants given an infusion of sodium chloride at conclusion of baseline experimental visit
Iron-deficient, given placeboSodium chloride (placebo)Iron-deficient participants given an infusion of sodium chloride at conclusion of baseline experimental visit
Iron-deficient, given ironFerric carboxymaltoseIron-deficient participants given an infusion of ferric carboxymaltose at conclusion of baseline experimental visit
Iron-replete, given ironFerric carboxymaltoseIron-deficient participants given an infusion of ferric carboxymaltose at conclusion of baseline experimental visit
Primary Outcome Measures
NameTimeMethod
Phosphocreatine depletion during small muscle mass exercise36 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 Outcome Measures
NameTimeMethod
Cardiopulmonary exercise test performanceHour 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

Participant reported symptomsAt 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

Muscle biopsy findingsImmediately 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)

Trial Locations

Locations (1)

University of Oxford OCMR & CCRF, John Radcliffe Hospital

🇬🇧

Oxford, Oxfordshire, United Kingdom

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