Effects of Iron Status, Manipulated Using Intravenous Iron, on Cardiopulmonary Physiology During Ascent to Very High Altitude
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 18
- 主要终点
- Change in right ventricular systolic pressure (RVSP) with altitude
研究概览
简要总结
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.
详细描述
Aim
The aim of the study was to investigate the effects of iron status on human cardiopulmonary physiology during ascent to very high altitude. Differences in iron status were brought about using intravenous iron, and outcomes were assessed using echocardiography and self-reported functional performance scores.
Objectives
Principal objective: To compare echocardiographic parameters in individuals of differing iron status during the expedition.
Secondary objectives: To compare physiological variables (oxygen saturation, pulse) and self-reported functional measures, in individuals of differing iron status during the expedition.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
盲法说明
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.
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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
排除标准
- •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.
研究组 & 干预措施
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.
干预措施: Ferric Carboxymaltose Injectable Product (Drug)
Saline control
Received a blinded single dose of iv normal saline 2 weeks prior to ascent to very high-altitude.
干预措施: Normal Saline 0.9% Infusion Solution Bag (Drug)
结局指标
主要结局
Change in right ventricular systolic pressure (RVSP) with altitude
时间窗: 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)
Change in time from pulmonary valve opening to peak pulmonary flow velocity with altitude
时间窗: 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).
Change in left ventricular stroke volume (LV SV) with altitude
时间窗: 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
Change in left ventricular index of myocardial performance (LIMP) with altitude
时间窗: 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.
Change in right ventricular index of myocardial performance (RIMP) with altitude
时间窗: 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.
Change in tissue Doppler velocity of the Right Ventricle (RV) and Left Ventricle (LV); units: cm/s, with altitude
时间窗: 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).
Change in tricuspid annulus planar systolic excursion (TAPSE) with altitude
时间窗: 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.
Change in right and left ventricular strain with altitude
时间窗: 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
次要结局
- Change in peripheral oxygen saturation with altitude(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))
- Change in haemoglobin level (g/dL) with altitude(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))
- Change in blood ferritin level (ug/L) with altitude(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))
- Change in heart rate with altitude(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))
- Change in transferrin saturation (%) with altitude(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))
- Change in soluble transferrin receptor level (nmol/L) with altitude(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))
- Change in hepcidin level (ng/mL) with altitude(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))
研究者
Lieutenant Colonel David Holdsworth
Lecturer in Military Medicine, Consultant Cardiologist and General Physician
Royal Centre for Defence Medicine