Iron and Muscle
Research type
Research Study
Full title
Multicentre prospective double-blind randomised controlled trial of the effect of intravenous iron supplementation, with or without exercise training, in iron-deficient but not anaemic patients with chronic kidney disease on exercise capacity, fatigue, skeletal muscle metabolism and physical function status.
IRAS ID
234820
Contact name
Kate Bramham
Contact email
Sponsor organisation
King's College Hospital NHS Foundation Trust
Eudract number
2018-000144-25
Duration of Study in the UK
3 years, 0 months, 0 days
Research summary
This is an exploratory study of a planned multi-centre RCT that will examine the efficacy of IV iron supplementation when compared to placebo, with and without exercise training, on changes in patient exercise capacity. The study aims to provide sufficient data to inform a power calculation for the definitive study to examine whether IV iron therapy in patients with CKD stages 3-4 (non-dialysis) can improve exercise capacity, muscle metabolism and physical function. Specifically, we propose to examine whether a strategy of IV iron therapy in patients with stages 3-4 CKD who are iron-deficient but NOT anaemic leads to improvements in exercise capacity.
Very little is currently known about the effects of iron deficiency on cardiac or skeletal muscle metabolism in patients suffering from CKD. Nevertheless, it seems likely that iron deficiency will contribute to mitochondrial dysfunction and reduced energy production in cardiac or skeletal muscle of CKD patients, and importantly may contribute to the reduced exercise capacity, physical function and overwhelming fatigue commonly reported in this population. The results of this trial will provide data to ascertain whether intravenous iron therapy might be beneficial to exercise capacity, muscle metabolism, physical function, and fatigue, and whether iron repletion enhances the effect of an exercise intervention.
Lay summary of study results: SP/Iron&Muscle/2018
What role for iron treatment in kidney disease patients? Many people with chronic kidney disease (CKD) have low levels of iron, even though they may not meet the medical criteria for a diagnosis of anaemia. Low iron levels are linked to physical symptoms, including feeling tired and muscle weakness. The Iron and Muscle study looked at whether iron supplementation could improve tiredness, biological measures of muscle function, exercise capacity and physical ability in this group of patients.A close look at the role of low iron levels in kidney disease patients The iron and muscle study, led by Dr Sharlene Greenwood and Dr Kate Bramham from King’s College Hospital NHS Trust and supported by Kidney Research UK, compared the impact of treatment with of IV iron and placebo (no treatment) on patients with stage 3-4 chronic kidney disease (CKD), who had reduced iron levels but were not considered anaemic. The study followed 75 individuals who were randomly assigned to a placebo or iron treatment group. Dr Greenwood and her team assessed a range of measures associated with iron deficiency; including how far the patients could walk in six minutes alongside their tiredness levels at the start of the study, and at four and 12 weeks. Laboratory based sub-studies took a closer look at how biological processes in muscle cells are affected by iron levels. What is iron and why is it important? Iron is a mineral that we gain through eating certain foods, Including red meat and beans, such as kidney beans. Iron is very important for the production of red blood cells, which carry oxygen around the body. Low blood iron is linked to reduced energy levels and muscle strength; when iron levels are very low, anaemia is diagnosed, and treatment can be given. Many people living with kidney disease are iron deficient, but not anaemic. The iron and muscle study looked at kidney disease patients with iron levels that were reduced, but not low enough to be classed as anaemia.
Clues for future research: This study found that reduced iron levels were associated with worse functioning of the part of skeletal muscle cells responsible for energy production (mitochondria). There is potential for improvements in exercise capacity, but a larger study with a longer follow-up would be needed to fully answer the question. No safety issues were reported in patients treated with iron. Dr Sharlene Greenwood commented: “There may be a role for treating low iron levels in people living with kidney disease, even without the presence of anaemia. Although further research is needed, there is a signal in our work that by treating reduced iron levels early, we may be able to support improvements in exercise capacity in patients living with CKD.REC name
London - Brent Research Ethics Committee
REC reference
19/LO/0128
Date of REC Opinion
8 Mar 2019
REC opinion
Further Information Favourable Opinion