Iron Status and Cardiopulmonary Physiology

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Brief Title

Iron Status and Cardiopulmonary Physiology

Official Title

Effects of Iron Status, Manipulated Using Intravenous Iron, on Cardiopulmonary Physiology During Ascent to Very High Altitude

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.
    

Detailed Description

      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.

      Hypotheses

      The primary hypothesis was that iron status, manipulated using intravenous iron, would
      influence the echocardiographic indices of cardiopulmonary physiological function over the
      course of the ascent.

      A secondary hypothesis was that iron status would influence cardiopulmonary responses in
      terms of pulse and oxygen saturation, and additionally the perceived exertion involved in
      ascent to very high altitude.

      Design of the Study

      The study randomised 18 individuals to iron or normal saline in a 1:1 ratio giving two groups
      of 9 people. The randomised infusion (control or iron) was undertaken at a pre-expedition
      meeting approximately 2 weeks prior to the flight to Nepal. The profile of ascent to high
      altitude will followed internationally accepted acclimatisation guidelines.

      Preliminary Testing

      To exclude elevated iron stores prior to enrollment, participants underwent an initial blood
      test. At the pre-exercise mounting station, prior to the flight to Nepal, baseline
      echocardiography was performed, and blood samples were collected immediately prior to
      randomisation and infusion. All blood samples in the study were analysed for full blood
      count, ferritin, iron, transferrin and C-reactive protein (CRP).

      Expedition-based tests

      Waking peripheral oxygen saturation (%) of haemoglobin (SpO2) and pulse were recorded daily.
      Venous blood samples were taken for later analysis of variables relevant to iron homeostasis
      including full blood count, erythropoietin, soluble transferrin receptor and hepcidin. These
      samples were taken in Kathmandu on the morning following arrival, at the intermediate staging
      camp (~3,200m) and then at the Dhaulagiri base camp on arrival and after descents from 6,000m
      and 7,000m.

      Measures of both left and right heart function were performed and included: pulmonary artery
      systolic pressure, pulmonary acceleration time, pulmonary regurgitation end diastolic
      velocity and tricuspid annular plane systolic excursion (distance of systolic excursion of
      the right ventricular annular plane towards the apex - TAPSE). Echo parameters were acquired
      and processed by an appropriately experienced researcher. Measures were taken during exercise
      on arrival at each test altitude and at rest the following morning. Measurements taken from
      climbers returning from either 6,000 m or 7,000 m were taken as soon as possible after their
      return to base camp.

      Subjective ratings scales include those for breathlessness (Borg 1-10) and perceived exertion
      (Borg 6-20).

      Blood sample storage and analysis

      Once drawn, venous blood was placed on ice. Following centrifugation (3,500 rpm for 10
      minutes at 4OC), aliquots of plasma were stored in cryogenic vials at -20°C. Samples drawn at
      high altitude were transported on dry ice or in liquid nitrogen 'dry-shippers' (safe liquid
      nitrogen containers that cannot leak nitrogen as liquid) back to the UK (United Kingdom).
      Subsequent analysis was performed at the University of Oxford.

      Statistical analysis

      Data were analysed using statistical tests with International Business Machines (IBM)
      'statistical package for social sciences' (SPSS) version 22 software.
    


Study Type

Interventional


Primary Outcome

Change in right ventricular systolic pressure (RVSP) with altitude

Secondary Outcome

 Change in peripheral oxygen saturation with altitude

Condition

Iron-deficiency

Intervention

Ferric Carboxymaltose Injectable Product

Study Arms / Comparison Groups

 Iron
Description:  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.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

18

Start Date

January 19, 2016

Completion Date

December 7, 2017

Primary Completion Date

May 1, 2016

Eligibility 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.
      

Gender

All

Ages

18 Years - 55 Years

Accepts Healthy Volunteers

Accepts Healthy Volunteers

Contacts

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Administrative Informations


NCT ID

NCT03707249

Organization ID

663/MODREC/15


Responsible Party

Principal Investigator

Study Sponsor

Royal Centre for Defence Medicine

Collaborators

 University of Oxford

Study Sponsor

, , 


Verification Date

October 2018