Iron Status and Human Metabolism

University of Oxford29 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

TRIPLE

Enrollment

Conditions

Iron Deficiency

Interventions

Ferric carboxymaltoseDRUG

Infusion of 15 mg/kg (up to maximum 1000 mg) ferric carboxymaltose in 250 mL 0.9% sodium chloride

Sodium chloride (placebo)DRUG

Infusion of 250 mL 0.9% sodium chloride

Eligibility

Sex: ALLMin age: 18 YearsHealthy volunteers:

Medical Language ↔ Plain English

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

Locations (1)

University of Oxford OCMR & CCRF, John Radcliffe Hospital

Oxford, Oxfordshire, United Kingdom

Outcomes

Primary Outcomes

Phosphocreatine depletion during small muscle mass exercise

Degree of phosphocreatine depletion during graded exercise of calf muscle assessed using magnetic resonance spectroscopy

Time frame: 36 minute long graded exercise test; performed at baseline and follow-up visits (approximately a week apart)

Secondary Outcomes

Cardiopulmonary exercise test performance

Blood lactate and cardiorespiratory parameters during moderate large skeletal muscle mass exercise, assessed with cardiopulmonary exercise testing

Time frame: 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)

Time frame: 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

Time frame: At study screening visit compared to four weeks following infusion of iron or placebo

Data from ClinicalTrials.gov

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