NCT02308449

Brief 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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
29

participants targeted

Target at below P25 for not_applicable

Timeline
Completed

Started Oct 2014

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

October 1, 2014

Completed
2 months until next milestone

First Submitted

Initial submission to the registry

November 21, 2014

Completed
13 days until next milestone

First Posted

Study publicly available on registry

December 4, 2014

Completed
12 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 1, 2015

Completed
1 month until next milestone

Study Completion

Last participant's last visit for all outcomes

January 1, 2016

Completed
Last Updated

July 19, 2022

Status Verified

July 1, 2022

Enrollment Period

1.2 years

First QC Date

November 21, 2014

Last Update Submit

July 15, 2022

Conditions

Iron Deficiency

Outcome Measures

Primary Outcomes (1)

  • 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 Outcomes (3)

  • Cardiopulmonary exercise test performance

    Hour long graded exercise test; performed at baseline and follow-up visits (approximately a week apart)

  • Muscle biopsy findings

    Immediately before and immediately after hour long cardiopulmonary exercise test, performed at baseline and follow-up visits (approximately a week apart)

  • Participant reported symptoms

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

Study Arms (4)

Iron-deficient, given placebo

PLACEBO COMPARATOR

Iron-deficient participants given an infusion of sodium chloride at conclusion of baseline experimental visit

Drug: Sodium chloride (placebo)

Iron-deficient, given iron

ACTIVE COMPARATOR

Iron-deficient participants given an infusion of ferric carboxymaltose at conclusion of baseline experimental visit

Drug: Ferric carboxymaltose

Iron-replete, given placebo

PLACEBO COMPARATOR

Iron-replete participants given an infusion of sodium chloride at conclusion of baseline experimental visit

Drug: Sodium chloride (placebo)

Iron-replete, given iron

ACTIVE COMPARATOR

Iron-deficient participants given an infusion of ferric carboxymaltose at conclusion of baseline experimental visit

Drug: Ferric carboxymaltose

Interventions

Ferric carboxymaltoseDRUG

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

Also known as: Ferinject
Iron-deficient, given ironIron-replete, given iron
Sodium chloride (placebo)DRUG

Infusion of 250 mL 0.9% sodium chloride

Also known as: Normal saline
Iron-deficient, given placeboIron-replete, given placebo

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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%

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

University of Oxford OCMR & CCRF, John Radcliffe Hospital

Oxford, Oxfordshire, OX3 9DU, United Kingdom

Location

Related Publications (6)

  • 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.

    PMID: 20616028BACKGROUND

  • Smith TG, Talbot NP, Privat C, Rivera-Ch M, Nickol AH, Ratcliffe PJ, Dorrington KL, Leon-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.

    PMID: 19809026BACKGROUND

  • 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.

    PMID: 18955380BACKGROUND

  • 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. doi: 10.1371/journal.pmed.0030290.

    PMID: 16768548BACKGROUND

  • 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. doi: 10.1172/JCI109431.

    PMID: 447849BACKGROUND

  • 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 phosphorylation. Sci Rep. 2022 Jan 19;12(1):998. doi: 10.1038/s41598-021-03968-4.

    PMID: 35046429RESULT

MeSH Terms

Conditions

Iron Deficiencies

Interventions

ferric carboxymaltoseSodium ChlorideSaline Solution

Condition Hierarchy (Ancestors)

Iron Metabolism DisordersMetabolic DiseasesNutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

ChloridesHydrochloric AcidChlorine CompoundsInorganic ChemicalsSodium CompoundsCrystalloid SolutionsIsotonic SolutionsSolutionsPharmaceutical Preparations

Study Officials

  • Peter A Robbins, DPhil

    University of Oxford

    STUDY DIRECTOR

  • Matthew C Frise, MRCP

    University of Oxford

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
BASIC SCIENCE
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

November 21, 2014

First Posted

December 4, 2014

Study Start

October 1, 2014

Primary Completion

December 1, 2015

Study Completion

January 1, 2016

Last Updated

July 19, 2022

Record last verified: 2022-07

Locations

GB(1)