This is a multi-center randomized controlled trial 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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
75
Active study medication Medication name: Ferinject® Active ingredient: Ferric carboxymaltose Dosage form: 50 mg iron/ml solution for injection/infusion. Appearance: Dark brown, non-transparent aqueous solution Excipients: Sodium hydroxide, hydrochloric acid and water for injection Strength/Packaging: Each 2 ml vial contains 100 mg of iron as ferric carboxymaltose. Each 10 ml vial contains 500 mg of iron as ferric carboxymaltose. Each 20 ml vial contains 1,000 mg of iron as ferric carboxymaltose. Manufacturer: Vifor Pharma UK Limited
Medication name: NaCl (sodium chloride 0.9%) Active ingredient: NaCl (sodium chloride 0.9%) Dosage form: 0.9% w/v NaCl as sterile solution in water for injection Excipients: Water Strength/Packaging: 100 ml container with 100 ml normal saline Manufacturer: As per local hospital supplier
King's College Hospital NHS Foundation Trust
London, United Kingdom
Exercise capacity as measured by 6 minute walk distance (6MWD)
An exercise capacity test
Time frame: 4 weeks
Haemoglobin levels
Haemoglobin
Time frame: 12 weeks
Iron status
Ferritin
Time frame: 12 weeks
Renal function
urea,
Time frame: 12 weeks
VO2 peak test (in a sub-set of participants)
To assess physical capacity
Time frame: 12 weeks
Isokinetic dynamometry (muscle strength)
To assess physical capacity
Time frame: 12 weeks
Functional capacity
sit-to-stand 60 to assess lower limb function
Time frame: 12 weeks
KDQOL-36
To assess quality of life by classifying patient general state of health. 1 - Excellent, 2 - Very Good, 3 - Good, 4 - Fair, 5 - Poor.
Time frame: 12 weeks
Skeletal muscle phosphocreatine recovery halftime (PCr t1/2) on MRI spectroscopy (n=40 patients at baseline and 4 weeks)
To assess skeletal muscle metabolism
Time frame: 12 weeks
The Work and Social Adjustment Scale (WSAS)
To assess quality of life by classifying out more about how participant fatigue impacts on their daily life 0 - Not at all, 1 to 2 - Slightly, 3 to 4 - Definitely, 5 to 6 - markedly and 7 to 8 - Very severely impaired /Cannot work
Time frame: 12 weeks
To assess the impact of iron regulatory genes e.g. HFE, TMPRSS6 etc. on the primary and secondary endpoints of the study (exploratory only)
Patients will be asked if they are willing to provide DNA from a single sample of whole blood to facilitate analysis of up to 90 iron regulatory genes, including HFE and TMPRSS. Iron regulatory gene expression measured by qPCR e.g. Hepcidin, Hemojuvelin, Ferroportin, Trf1 receptor, and iron regulatory proteins-1 \& -2.
Time frame: 12 Weeks
Iron Status
TSAT
Time frame: 12 weeks
Renal Function
creatinine
Time frame: 12 weeks
Renal Function
estimated glomerular filtration rate to be used to determine renal function
Time frame: 12 weeks
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