<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT02252627</url>
  </required_header>
  <id_info>
    <org_study_id>H10102013</org_study_id>
    <nct_id>NCT02252627</nct_id>
  </id_info>
  <brief_title>The Effect of Phenylephrine and Ephedrine on Microvascular Blood Flow</brief_title>
  <official_title>An Observational Study to Test the Effect of the Vasoactive Drugs Phenylephrine and Ephedrine on the Stroke Volume and Microvascular Blood Flow of Healthy Volunteers</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Nottingham</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Nottingham</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      During operations to treat abdominal problems the blood pressure can fall, resulting in falls&#xD;
      in blood flow to the vital organs. This fall can be treated by the administration of drugs&#xD;
      that cause constriction of blood vessels. Although these drugs correct falls in blood&#xD;
      pressure, it is unclear what effect they have on blood flow from the heart and to the vital&#xD;
      organs.&#xD;
&#xD;
      In this study of healthy volunteers we aim to better understand the changes in blood flow in&#xD;
      both small and large vessels that occur in response to administration of these drugs. To do&#xD;
      this we will use two different techniques of ultrasound imaging. A narrow (4-5mm) ultrasound&#xD;
      probe will be inserted into the oesophagus via a nostril to measure blood flow in a major&#xD;
      blood vessel. A second probe will rest on the abdomen and will record changes in blood flow&#xD;
      in small vessels of the liver. Two drugs which raise the blood pressure via different&#xD;
      mechanisms will be administered and the changes in flow from the heart and to vital organs&#xD;
      will be measured and compared.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Optimising the cardiac output is essential to ensure adequate organ perfusion in patients who&#xD;
      are undergoing major surgery. To enable this cardiac output (CO) is frequently monitored&#xD;
      during operations using a variety of techniques; one such technique is trans-oesophageal&#xD;
      Doppler ultrasound also known as oesophageal Doppler monitoring (ODM). ODM measurement of CO&#xD;
      is a less invasive technique than many currently used methods, and has recently been&#xD;
      recommended by NICE for adoption in clinical practice. The matching of microvascular blood&#xD;
      flow and CO is advantageous for visceral organs, in marrying demands for oxygen and nutrients&#xD;
      to their delivery. Major surgery and the attendant requirement for general anaesthesia can&#xD;
      result in dramatic changes in blood pressure (BP) and CO. These changes can be corrected by&#xD;
      the administration of vasoactive drugs such as phenylephrine and ephedrine, although it is&#xD;
      unclear what effects these drugs have on microvascular blood flow (MVBF) to the&#xD;
      intra-abdominal viscera. Whilst they correct falls in BP, and hence may increase visceral&#xD;
      flow, this increased BP is partially mediated via splanchnic vasoconstriction, which may&#xD;
      result in decreased blood flow. A greater appreciation of the effect of these vasoactive&#xD;
      drugs on the CO and MVBF may help with the development of more refined algorithms for their&#xD;
      use in the clinical setting. In our clinical physiology laboratories we regularly employ&#xD;
      contrast-enhanced ultrasound (CEUS) using a Phillips iU22, to measure MVBF in healthy males&#xD;
      following a variety of physiological challenges. This minimally invasive ultrasound based&#xD;
      imaging technique is ideal for gaining an insight into the effect various physiological&#xD;
      interventions have on tissue blood flow and could be readily used to chart changes in&#xD;
      visceral MVBF and CO following vasoactive drug administration. Transference of this&#xD;
      investigative approach to a clinical setting has the potential to greatly improve the care of&#xD;
      the surgical patient under anaesthesia.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date>August 2014</start_date>
  <completion_date type="Anticipated">August 2015</completion_date>
  <primary_completion_date type="Anticipated">August 2015</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Change in microvascular blood flow</measure>
    <time_frame>30 minutes</time_frame>
    <description>Microvascular visceral blood flow is assessed using contrast enhanced ultrasound, and will be assessed before and after the administration of each drug.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in stroke volume</measure>
    <time_frame>30 mins</time_frame>
    <description>The change in stroke volume will be assessed using an Oesophageal Doppler Monitor, and will be assessed before and after the administration of each drug.</description>
  </secondary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Anticipated">8</enrollment>
  <condition>Healthy Volunteers</condition>
  <arm_group>
    <arm_group_label>Group 1</arm_group_label>
    <description>Healthy volunteers</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Administration of phenylephrine</intervention_name>
    <description>Intravenous phenylephrine will be administered in 50-100 microgram increments until the mean arterial blood pressure has increased by 25% compared to baseline, or until a maximum dose of 1mg has been administered.</description>
    <arm_group_label>Group 1</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Measurement of stroke volume</intervention_name>
    <description>The measurement of stroke volume will be performed using an Oesophageal Doppler Monitor</description>
    <arm_group_label>Group 1</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Contrast enhanced ultrasound scan</intervention_name>
    <description>Microvascular blood flow will be measured using a contrast enhanced ultrasound scan</description>
    <arm_group_label>Group 1</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Administration of ephedrine</intervention_name>
    <description>Intravenous ephedrine will be administered in 3-6mg increments until the mean arterial blood pressure has increased by 25% compared to baseline, or until a maximum dose of 30mg has been administered.</description>
    <arm_group_label>Group 1</arm_group_label>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        Healthy male volunteers&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Aged 18-60 years&#xD;
&#xD;
          -  Male&#xD;
&#xD;
          -  Able to consent in English by themselves&#xD;
&#xD;
          -  Absence of any exclusion criteria&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  A BMI &lt; 20 or &gt; 28 kg•m2&#xD;
&#xD;
          -  Active cardiovascular disease: uncontrolled hypertension (BP &gt; 140/90), angina, heart&#xD;
             failure (class III/IV), arthymia, right to left cardiac shunt or recent cardiac event&#xD;
&#xD;
          -  Individuals taking alpha or beta-adrenergic blocking agents, monoamine oxidase&#xD;
             inhibitors, tricyclic antidepressants, serotonin or noradrenaline selective reuptake&#xD;
             inhibitors, quinidine, cardiac glycosides or buspirone (or who have ceased taking them&#xD;
             in the previous 14 days¬)&#xD;
&#xD;
          -  Cerebrovascular disease: previous stroke, aneurysm (large vessel or intracranial)&#xD;
&#xD;
          -  Peripheral vascular disease&#xD;
&#xD;
          -  Metabolic disease: hyper and hypo parathyroidism, untreated hyper and hypothyroidism,&#xD;
             Cushing's disease, types 1 or 2 diabetes&#xD;
&#xD;
          -  Active inflammatory bowel disease, or renal disease&#xD;
&#xD;
          -  Known prostatic hypertrophy&#xD;
&#xD;
          -  Malignancy&#xD;
&#xD;
          -  Clotting dysfunction&#xD;
&#xD;
          -  Previous oesophageal surgery&#xD;
&#xD;
          -  Individuals with a known history of oesophageal varices&#xD;
&#xD;
          -  Individuals with a known history of epistaxis&#xD;
&#xD;
          -  Family history of early (&lt;55y) death from cardiovascular disease&#xD;
&#xD;
          -  Known sensitivity to SonoVue, ephedrine or phenylephrine&#xD;
&#xD;
          -  Participants who have taken part in any other research study in the last three months&#xD;
             which involved: taking a drug; being paid a disturbance allowance; having an invasive&#xD;
             procedure (eg blood sample &gt;50ml, muscle biopsies) or exposure to ionising radiation.&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>60 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>John P Williams, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Nottingham</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>John P Williams, PhD</last_name>
    <email>john.williams7@nhs.net</email>
  </overall_contact>
  <location>
    <facility>
      <name>University of Nottingham, School of Medicine, Division of Medical Sciences and Graduate Entry Medicine</name>
      <address>
        <city>Derby</city>
        <state>Derbyshire</state>
        <zip>DE22 3DT</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>David Read, BMBS</last_name>
      <email>dread1@nhs.net</email>
    </contact>
    <investigator>
      <last_name>John P Williams, PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Thomas P Heinink, BMBS</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Jonathan N Lund, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Bethan E Phillips, PhD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>David Read, BMBS</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>January 2015</verification_date>
  <study_first_submitted>September 25, 2014</study_first_submitted>
  <study_first_submitted_qc>September 25, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 30, 2014</study_first_posted>
  <last_update_submitted>January 26, 2015</last_update_submitted>
  <last_update_submitted_qc>January 26, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">January 27, 2015</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Phenylephrine</mesh_term>
    <mesh_term>Oxymetazoline</mesh_term>
    <mesh_term>Ephedrine</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02252627
org study id: H10102013
nct id: NCT02252627
lead sponsor: 
has dmc: No
During operations to treat abdominal problems the blood pressure can fall, resulting in falls
      in blood flow to the vital organs. This fall can be treated by the administration of drugs
      that cause constriction of blood vessels. Although these drugs correct falls in blood
      pressure, it is unclear what effect they have on blood flow from the heart and to the vital
      organs.

      In this study of healthy volunteers we aim to better understand the changes in blood flow in
      both small and large vessels that occur in response to administration of these drugs. To do
      this we will use two different techniques of ultrasound imaging. A narrow (4-5mm) ultrasound
      probe will be inserted into the oesophagus via a nostril to measure blood flow in a major
      blood vessel. A second probe will rest on the abdomen and will record changes in blood flow
      in small vessels of the liver. Two drugs which raise the blood pressure via different
      mechanisms will be administered and the changes in flow from the heart and to vital organs
      will be measured and compared.
Optimising the cardiac output is essential to ensure adequate organ perfusion in patients who
      are undergoing major surgery. To enable this cardiac output (CO) is frequently monitored
      during operations using a variety of techniques; one such technique is trans-oesophageal
      Doppler ultrasound also known as oesophageal Doppler monitoring (ODM). ODM measurement of CO
      is a less invasive technique than many currently used methods, and has recently been
      recommended by NICE for adoption in clinical practice. The matching of microvascular blood
      flow and CO is advantageous for visceral organs, in marrying demands for oxygen and nutrients
      to their delivery. Major surgery and the attendant requirement for general anaesthesia can
      result in dramatic changes in blood pressure (BP) and CO. These changes can be corrected by
      the administration of vasoactive drugs such as phenylephrine and ephedrine, although it is
      unclear what effects these drugs have on microvascular blood flow (MVBF) to the
      intra-abdominal viscera. Whilst they correct falls in BP, and hence may increase visceral
      flow, this increased BP is partially mediated via splanchnic vasoconstriction, which may
      result in decreased blood flow. A greater appreciation of the effect of these vasoactive
      drugs on the CO and MVBF may help with the development of more refined algorithms for their
      use in the clinical setting. In our clinical physiology laboratories we regularly employ
      contrast-enhanced ultrasound (CEUS) using a Phillips iU22, to measure MVBF in healthy males
      following a variety of physiological challenges. This minimally invasive ultrasound based
      imaging technique is ideal for gaining an insight into the effect various physiological
      interventions have on tissue blood flow and could be readily used to chart changes in
      visceral MVBF and CO following vasoactive drug administration. Transference of this
      investigative approach to a clinical setting has the potential to greatly improve the care of
      the surgical patient under anaesthesia.
time perspective: Prospective
measure: Change in microvascular blood flow
time frame: 30 minutes
description: Microvascular visceral blood flow is assessed using contrast enhanced ultrasound, and will be assessed before and after the administration of each drug.
measure: Change in stroke volume
time frame: 30 mins
description: The change in stroke volume will be assessed using an Oesophageal Doppler Monitor, and will be assessed before and after the administration of each drug.
arm group label: Group 1
description: Healthy volunteers
intervention type: Drug
intervention name: Administration of phenylephrine
description: Intravenous phenylephrine will be administered in 50-100 microgram increments until the mean arterial blood pressure has increased by 25% compared to baseline, or until a maximum dose of 1mg has been administered.
arm group label: Group 1
intervention type: Other
intervention name: Measurement of stroke volume
description: The measurement of stroke volume will be performed using an Oesophageal Doppler Monitor
arm group label: Group 1
intervention type: Other
intervention name: Contrast enhanced ultrasound scan
description: Microvascular blood flow will be measured using a contrast enhanced ultrasound scan
arm group label: Group 1
intervention type: Drug
intervention name: Administration of ephedrine
description: Intravenous ephedrine will be administered in 3-6mg increments until the mean arterial blood pressure has increased by 25% compared to baseline, or until a maximum dose of 30mg has been administered.
arm group label: Group 1
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: Male
minimum age: 18 Years
maximum age: 60 Years
healthy volunteers: Accepts Healthy Volunteers
last name: John P Williams, PhD
role: Principal Investigator
affiliation: University of Nottingham
last name: John P Williams, PhD
email: john.williams7@nhs.net
facility: 
status: Recruiting
contact: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
country: United Kingdom
responsible party type: Sponsor
mesh term: Phenylephrine
mesh term: Oxymetazoline
mesh term: Ephedrine