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Completed

NCT Number: NCT04862715

The Iron and Muscle Study

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.

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Key information

Conditions

CKD Stage 3 Anemia Anemia, Hypochromic Anemia, Iron-Deficiency CKD Stage 4 Hematologic Diseases Hemic and Lymphatic Diseases Iron Deficiencies Iron Metabolism Disorders Iron-deficiency Metabolic Diseases Nutritional and Metabolic Diseases

Age range

18 year–80 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

Primary location

King's College Hospital NHS Foundation Trust

London, SE5 9RS, United Kingdom

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Patients with established CKD (Stages 3-4) not on dialysis
  • Resting BP ≤ 160/95mmHg
  • Men and women aged 18 - 80 years
  • Serum ferritin level less than 100μg/L AND/OR transferrin saturation ≤20%
  • Haemoglobin 110 - 150 g/L

Exclusion criteria

  • Pregnancy or breast feeding (Female patients of childbearing age will be asked if there is any possibility they may be pregnant. This is standard of care and no pregnancy test will be requested unless there is doubt about this. IV iron is given to many pregnant patients in standard treatment and there is no evidence of harm to mother or foetus).
  • Weight < 50kg
  • Known allergy to iron therapy
  • Haemochromatosis, porphyria cutanea tarda or history of acquired iron overload
  • Intravenous iron within previous 6 weeks
  • CRP > 50 mg/L
  • Serum phosphate < 0.7 mmol/L.
  • Active infection
  • Current therapy with ESAs
  • Uncontrolled atrial fibrillation
  • Use of anticoagulants in those under consideration for muscle biopsy
  • Unstable angina or heart attack within the last year
  • Presence of solid organ cancer
  • Known haemoglobinopathy, myelodysplasia, or myeloma
  • Patients with peripheral vascular or musculoskeletal disease, who the investigator deems unable to carry out the 6MWT.
  • Known severe aortic stenosis and pacemaker in-situ
  • History of severe atopy
  • Severe liver disease with serum transaminases > x3 upper limit of normal range according to local laboratory values.
  • Severe lung disease with FEV1 known to be <50% predicted in last year
  • Known heart failure with a left ventricular ejection fraction <45% in last year
  • Any other health condition considered by the local Principal Investigator in which IV iron will be contraindicated.
  • Insufficient understanding of the trial

Treatment and study plan

Ferinject

Drug

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

Placebo: NaCl (sodium chloride 0.9%)

Other

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

Primary outcomes

  1. Exercise capacity as measured by 6 minute walk distance (6MWD)

    Time frame: 4 weeks

    An exercise capacity test

Secondary outcomes

  1. Haemoglobin levels

    Time frame: 12 weeks

    Haemoglobin

  2. Iron status

    Time frame: 12 weeks

    Ferritin

  3. Renal function

    Time frame: 12 weeks

    urea,

  4. VO2 peak test (in a sub-set of participants)

    Time frame: 12 weeks

    To assess physical capacity

  5. Isokinetic dynamometry (muscle strength)

    Time frame: 12 weeks

    To assess physical capacity

  6. Functional capacity

    Time frame: 12 weeks

    sit-to-stand 60 to assess lower limb function

  7. KDQOL-36

    Time frame: 12 weeks

    To assess quality of life by classifying patient general state of health. 1 - Excellent, 2 - Very Good, 3 - Good, 4 - Fair, 5 - Poor.

  8. Skeletal muscle phosphocreatine recovery halftime (PCr t1/2) on MRI spectroscopy (n=40 patients at baseline and 4 weeks)

    Time frame: 12 weeks

    To assess skeletal muscle metabolism

  9. The Work and Social Adjustment Scale (WSAS)

    Time frame: 12 weeks

    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

  10. To assess the impact of iron regulatory genes e.g. HFE, TMPRSS6 etc. on the primary and secondary endpoints of the study (exploratory only)

    Time frame: 12 Weeks

    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.

  11. Iron Status

    Time frame: 12 weeks

    TSAT

  12. Renal Function

    Time frame: 12 weeks

    creatinine

  13. Renal Function

    Time frame: 12 weeks

    estimated glomerular filtration rate to be used to determine renal function

Sponsors and collaborators

Lead sponsor

King's College Hospital NHS Trust

Other

Collaborators

  • King's College London
  • University of Leicester

Registry information

Official study title

Multicentre Prospective Double-blind Randomised Controlled Trial of the Effect of Intravenous Iron Supplementation and Exercise Training in Iron-deficient, But Not Anaemic, Patients With Chronic Kidney Disease on Exercise Capacity, Physical Function, Fatigue, and Skeletal Muscle Metabolism

Important dates

Study start
2019
Primary completion
2021
Study completion
2022
First posted
Apr 28, 2021
Registry last updated
Mar 2, 2022

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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