Effects of Endogenous Iron Status and Intravenous Iron on Human Skeletal Muscle Metabolism at Rest and During Exercise
Overview
- Phase
- Not Applicable
- Intervention
- Sodium chloride (placebo)
- Conditions
- Iron Deficiency
- Sponsor
- University of Oxford
- Enrollment
- 29
- Locations
- 1
- Primary Endpoint
- Phosphocreatine depletion during small muscle mass exercise
- Status
- Completed
- Last Updated
- 3 years ago
Overview
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.
Investigators
Eligibility Criteria
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
Arms & Interventions
Iron-deficient, given placebo
Iron-deficient participants given an infusion of sodium chloride at conclusion of baseline experimental visit
Intervention: Sodium chloride (placebo)
Iron-deficient, given iron
Iron-deficient participants given an infusion of ferric carboxymaltose at conclusion of baseline experimental visit
Intervention: Ferric carboxymaltose
Iron-replete, given placebo
Iron-replete participants given an infusion of sodium chloride at conclusion of baseline experimental visit
Intervention: Sodium chloride (placebo)
Iron-replete, given iron
Iron-deficient participants given an infusion of ferric carboxymaltose at conclusion of baseline experimental visit
Intervention: Ferric carboxymaltose
Outcomes
Primary Outcomes
Phosphocreatine depletion during small muscle mass exercise
Time Frame: 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 Outcomes
- Cardiopulmonary exercise test performance(Hour long graded exercise test; performed at baseline and follow-up visits (approximately a week apart))
- Participant reported symptoms(At study screening visit compared to four weeks following infusion of iron or placebo)
- Muscle biopsy findings(Immediately before and immediately after hour long cardiopulmonary exercise test, performed at baseline and follow-up visits (approximately a week apart))