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Iron Status and Cardiopulmonary Physiology

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ClinicalTrials.gov Identifier: NCT03707249
Recruitment Status : Completed
First Posted : October 16, 2018
Last Update Posted : October 18, 2018
Sponsor:
Collaborator:
University of Oxford
Information provided by (Responsible Party):
Lieutenant Colonel David Holdsworth, Royal Centre for Defence Medicine

Brief Summary:
This study involved human volunteers undertaking a high-altitude expedition. It assessed changes in physiological parameters of relevance to high-altitude cardiopulmonary physiology. Participants included a subgroup of those taking part in an existing adventurous training expedition and were randomised in a 1:1 fashion to receive either intravenous iron or normal saline several weeks prior to departure. During the expedition, participants were investigated by means of transthoracic echocardiography, peripheral oxygen saturation measurement and heart rate monitoring and through the drawing of venous blood samples. Bloods were later analysed for markers of iron status.

Condition or disease Intervention/treatment Phase
Iron-deficiency Ventricular Function Pulmonary Vascular Resistance Abnormality Altitude Hypoxia Drug: Ferric Carboxymaltose Injectable Product Drug: Normal Saline 0.9% Infusion Solution Bag Not Applicable

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 18 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: 2 groups were randomised to receive a dose of intravenous iron or iv saline control to manipulate body iron stores. They were subsequently investigated non-invasively and with venous blood sampling during an ascent to very high altitude.
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Masking Description: Participants were blinded by the use of eye-masks during infusion and the physical covering of infusion bags and giving sets. Investigators were unaware of the allocation to iron or saline control. Outcomes assessors were also unaware of the allocation.
Primary Purpose: Basic Science
Official Title: Effects of Iron Status, Manipulated Using Intravenous Iron, on Cardiopulmonary Physiology During Ascent to Very High Altitude
Actual Study Start Date : January 19, 2016
Actual Primary Completion Date : May 1, 2016
Actual Study Completion Date : December 7, 2017

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Iron

Arm Intervention/treatment
Experimental: Iron
Received a blinded single 15 mg/kg dose of iv ferric carboxymaltose (Ferinject) up to a maximum off 1g total dose 2 weeks prior to ascent to very high-altitude.
Drug: Ferric Carboxymaltose Injectable Product
iv iron infusion: 15 mg / kg up to a maximum 1g dose of Ferinject diluted in normal saline (0.9%) up to a total volume of 250 ml
Other Name: Ferinject

Sham Comparator: Saline control
Received a blinded single dose of iv normal saline 2 weeks prior to ascent to very high-altitude.
Drug: Normal Saline 0.9% Infusion Solution Bag
250 ml of normal (0.9%) saline given by intravenous infusion over 20 minutes. This constitutes the control for the iron infusion.




Primary Outcome Measures :
  1. Change in right ventricular systolic pressure (RVSP) with altitude [ Time Frame: Measurement performed at baseline (2 weeks prior to commencing ascent to very high altitude) and at intervals during ascent to very high altitude (over a period of 2 weeks) ]
    Non-invasive measurement of Right ventricular systolic pressure (mmHg) estimated from the velocity of tricuspid regurgitation (TR) (m/s) measured during transthoracic echocardiographic (TTE) continuous wave (CW) Doppler assessment of the tricuspid valve regurgitant jet (RVSP = TR velocity^2 * 4)

  2. Change in time from pulmonary valve opening to peak pulmonary flow velocity with altitude [ Time Frame: Measurement performed at baseline (2 weeks prior to commencing ascent to very high altitude) and at intervals during ascent to very high altitude (over a period of 2 weeks) ]
    The time from pulmonary valve opening to peak velocity flow is inversely correlated with pulmonary artery pressure. This time is measured on a pulsed wave (PW) Doppler trace in the parasternal short axis view at the pulmonary valve level. The measurement is a time and the units are ms. Categories are: normal (>130 ms), borderline elevated (100-130 ms), elevated (80-100 ms) and severely elevated (<80 ms).

  3. Change in left ventricular stroke volume (LV SV) with altitude [ Time Frame: Measurement performed at baseline (2 weeks prior to commencing ascent to very high altitude) and at intervals during ascent to very high altitude (over a period of 2 weeks) ]
    The stroke volume of the left ventricle is calculated from 2-D parasternal echocardiographic measurement of the left ventricular outflow tract diameter (LVOT) and pulsed wave (PW) Doppler measurement of the flow through the LVOT during systole. PW of the LVOT allows measurement of the velocity.time integral of the LVOT flow (VTI). This value, when multiplied by the cross sectional area of the LVOT, allows an extimate of stroke volume. SV = (Pi*(radius of LVOT^2))*VTI of LVOT

  4. Change in left ventricular index of myocardial performance (LIMP) with altitude [ Time Frame: Measurement performed at baseline (2 weeks prior to commencing ascent to very high altitude) and at intervals during ascent to very high altitude (over a period of 2 weeks) ]
    This is a non-invasive measurement of left ventricular function made by transthoracic echocardiography (TTE). Tissue Doppler imaging (TDI) is used to measure the behaviour of the left ventricle throughout the cardiac cycle (both systole and diastole). This allows the time (ms) of isovolumic contraction time (ICT), isovolumic relaxation time (IVRT) and ejection time (ET). The LIMP (also known as Tei index) = IVCT+IVRT/ET. It is a global measure of systolic and diastolic function of the heart.

  5. Change in right ventricular index of myocardial performance (RIMP) with altitude [ Time Frame: Measurement performed at baseline (2 weeks prior to commencing ascent to very high altitude) and at intervals during ascent to very high altitude (over a period of 2 weeks) ]
    This is a non-invasive measurement of right ventricular function made by transthoracic echocardiography (TTE). Tissue Doppler imaging (TDI) is used to measure the behaviour of the left ventricle throughout the cardiac cycle (both systole and diastole). This allows the time (ms) of isovolumic contraction time (ICT), isovolumic relaxation time (IVRT) and ejection time (ET). The RIMP = IVCT+IVRT/ET. It is a global measure of systolic and diastolic function of the heart.

  6. Change in tissue Doppler velocity of the Right Ventricle (RV) and Left Ventricle (LV); units: cm/s, with altitude [ Time Frame: Measurement performed at baseline (2 weeks prior to commencing ascent to very high altitude) and at intervals during ascent to very high altitude (over a period of 2 weeks) ]
    Tissue Doppler imaging (TDI) is performed on the ventricular myocardium 1cm apical to the atrioventricular valve annulus (either the tricuspid valve annulus, for the RV assessment, or the LV septum and LV lateral wall adjacent to the mitral valve for the LV assessment). The parameters are peak systolic velocity (s', cm/s), peak velocity during early diastole (e', cm/s) and peak velocity during atrial systole (a', cm/s).

  7. Change in tricuspid annulus planar systolic excursion (TAPSE) with altitude [ Time Frame: Measurement performed at baseline (2 weeks prior to commencing ascent to very high altitude) and at intervals during ascent to very high altitude (over a period of 2 weeks) ]
    This is a Doppler M-mode measurement of the full range of movement of the tricuspid annulus at the right ventricular (RV) free wall throughout the cardiac cycle. It is measured by placing an M-mode cursor through the connection of the tricuspid annulus to the RV free wall and measuring the basal-apical excursion of the annulus at this point, from end diastole until the most apical point that it reaches in systole. It is a measure of systolic RV function. Its units are cm.

  8. Change in right and left ventricular strain with altitude [ Time Frame: Measurement performed at baseline (2 weeks prior to commencing ascent to very high altitude) and at intervals during ascent to very high altitude (over a period of 2 weeks) ]
    Non-invasive tissue Doppler measurements are acquired on apical 4-chamber, apical 2-chamber and apical 3-chamber images throughout 3 cardiac cycles to allow later analysis to determine the longitudinal strain of the right and left ventricle


Secondary Outcome Measures :
  1. Change in peripheral oxygen saturation with altitude [ Time Frame: Measurement performed at baseline (2 weeks prior to commencing ascent to very high altitude) and at intervals during ascent to very high altitude (over a period of 2 weeks) ]
    Peripheral oxygen saturation measured using a non-invasive portable, fingertip pulse oximeter

  2. Change in heart rate with altitude [ Time Frame: Measurement performed at baseline (2 weeks prior to commencing ascent to very high altitude) and at intervals during ascent to very high altitude (over a period of 2 weeks) ]
    Heart rate measured by 3 lead ECG monitor connected to a portable transthoracic echocardiography machine

  3. Change in blood ferritin level (ug/L) with altitude [ Time Frame: Measurement performed at baseline (2 weeks prior to commencing ascent to very high altitude) and at intervals during ascent to very high altitude (over a period of 2 weeks) ]
    Venous blood samples analysed for ferritin

  4. Change in haemoglobin level (g/dL) with altitude [ Time Frame: Measurement performed at baseline (2 weeks prior to commencing ascent to very high altitude) and at intervals during ascent to very high altitude (over a period of 2 weeks) ]
    Venous blood samples analysed for haemoglobin

  5. Change in transferrin saturation (%) with altitude [ Time Frame: Measurement performed at baseline (2 weeks prior to commencing ascent to very high altitude) and at intervals during ascent to very high altitude (over a period of 2 weeks) ]
    Venous blood samples analysed for transferrin and iron to allow the calculation of the transferrin saturation, listed as a percentage

  6. Change in soluble transferrin receptor level (nmol/L) with altitude [ Time Frame: Measurement performed at baseline (2 weeks prior to commencing ascent to very high altitude) and at intervals during ascent to very high altitude (over a period of 2 weeks) ]
    Venous blood samples analysed for soluble transferrin receptor

  7. Change in hepcidin level (ng/mL) with altitude [ Time Frame: Measurement performed at baseline (2 weeks prior to commencing ascent to very high altitude) and at intervals during ascent to very high altitude (over a period of 2 weeks) ]
    Venous blood samples analysed for hepcidin



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Healthy non-pregnant adults
  • Age 18-55 years
  • Serving in the UK Armed Forces
  • Selected for a military mountaineering team intending to climb to very high altitude

Exclusion Criteria:

  • Diabetes
  • Any cardiovascular or respiratory illness
  • Regular medication which would interfere with any outcome measures in the study
  • Pregnancy
  • Any condition which precludes the administration of Ferinject:

    (i) hypersensitivity to the active substance, to Ferinject® or any of its excipients (ii) known serious hypersensitivity to other parenteral iron products (iii) microcytic anaemia not attributable to iron deficiency (e.g. sickle cell anaemia) (iv) evidence of iron overload or disturbances in the utilisation of iron.

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Responsible Party: Lieutenant Colonel David Holdsworth, Lecturer in Military Medicine, Consultant Cardiologist and General Physician, Royal Centre for Defence Medicine
ClinicalTrials.gov Identifier: NCT03707249    
Other Study ID Numbers: 663/MODREC/15
First Posted: October 16, 2018    Key Record Dates
Last Update Posted: October 18, 2018
Last Verified: October 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Altitude Sickness
Hypoxia
Signs and Symptoms, Respiratory
Respiration Disorders
Respiratory Tract Diseases
Ferric Compounds
Hematinics