Iron Status and Human Metabolism

Iron Deficiency Clinical Trial

Official title:

Effects of Endogenous Iron Status and Intravenous Iron on Human Skeletal Muscle Metabolism at Rest and During Exercise

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02308449
• Other study ID #: 13/SC/0439
• Status: Completed
• Phase: N/A
• Start date: October 2014
• Est. completion date: January 2016

Study information

• Verified date: July 2022
• Source: University of Oxford
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 29
• Est. completion date: January 2016
• Est. primary completion date: December 2015
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Anemia, Iron-Deficiency
• Iron Deficiency

Intervention

Drug:
• Ferric carboxymaltose
Infusion of 15 mg/kg (up to maximum 1000 mg) ferric carboxymaltose in 250 mL 0.9% sodium chloride
• Sodium chloride (placebo)
Infusion of 250 mL 0.9% sodium chloride

Locations

Country	Name	City	State
United Kingdom	University of Oxford OCMR & CCRF, John Radcliffe Hospital	Oxford	Oxfordshire

Sponsors (3)

Lead Sponsor	Collaborator
University of Oxford	British Heart Foundation, National Institute for Health Research, United Kingdom

Country where clinical trial is conducted

United Kingdom, 

References & Publications (6)

Finch CA, Gollnick PD, Hlastala MP, Miller LR, Dillmann E, Mackler B. Lactic acidosis as a result of iron deficiency. J Clin Invest. 1979 Jul;64(1):129-37. — View Citation

Formenti F, Constantin-Teodosiu D, Emmanuel Y, Cheeseman J, Dorrington KL, Edwards LM, Humphreys SM, Lappin TR, McMullin MF, McNamara CJ, Mills W, Murphy JA, O'Connor DF, Percy MJ, Ratcliffe PJ, Smith TG, Treacy M, Frayn KN, Greenhaff PL, Karpe F, Clarke K, Robbins PA. Regulation of human metabolism by hypoxia-inducible factor. Proc Natl Acad Sci U S A. 2010 Jul 13;107(28):12722-7. doi: 10.1073/pnas.1002339107. Epub 2010 Jun 28. — View Citation

Frise MC, Holdsworth DA, Johnson AW, Chung YJ, Curtis MK, Cox PJ, Clarke K, Tyler DJ, Roberts DJ, Ratcliffe PJ, Dorrington KL, Robbins PA. Abnormal whole-body energy metabolism in iron-deficient humans despite preserved skeletal muscle oxidative phosphory — View Citation

Smith TG, Balanos GM, Croft QP, Talbot NP, Dorrington KL, Ratcliffe PJ, Robbins PA. The increase in pulmonary arterial pressure caused by hypoxia depends on iron status. J Physiol. 2008 Dec 15;586(24):5999-6005. doi: 10.1113/jphysiol.2008.160960. Epub 2008 Oct 27. — View Citation

Smith TG, Brooks JT, Balanos GM, Lappin TR, Layton DM, Leedham DL, Liu C, Maxwell PH, McMullin MF, McNamara CJ, Percy MJ, Pugh CW, Ratcliffe PJ, Talbot NP, Treacy M, Robbins PA. Mutation of von Hippel-Lindau tumour suppressor and human cardiopulmonary physiology. PLoS Med. 2006 Jul;3(7):e290. — View Citation

Smith TG, Talbot NP, Privat C, Rivera-Ch M, Nickol AH, Ratcliffe PJ, Dorrington KL, León-Velarde F, Robbins PA. Effects of iron supplementation and depletion on hypoxic pulmonary hypertension: two randomized controlled trials. JAMA. 2009 Oct 7;302(13):1444-50. doi: 10.1001/jama.2009.1404. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Phosphocreatine depletion during small muscle mass exercise	Degree of phosphocreatine depletion during graded exercise of calf muscle assessed using magnetic resonance spectroscopy	36 minute long graded exercise test; performed at baseline and follow-up visits (approximately a week apart)
Secondary	Cardiopulmonary exercise test performance	Blood lactate and cardiorespiratory parameters during moderate large skeletal muscle mass exercise, assessed with cardiopulmonary exercise testing	Hour long graded exercise test; performed at baseline and follow-up visits (approximately a week apart)
Secondary	Muscle biopsy findings	Skeletal muscle characteristics, assessed by minimally-invasive muscle biopsy (not a compulsory part of the protocol)	Immediately before and immediately after hour long cardiopulmonary exercise test, performed at baseline and follow-up visits (approximately a week apart)
Secondary	Participant reported symptoms	Measures of fatigue, restless-legs syndrome and well-being assessed by self-reported questionnaires	At study screening visit compared to four weeks following infusion of iron or placebo