<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/NCT03298880</url>
  </required_header>
  <id_info>
    <org_study_id>1617/043</org_study_id>
    <nct_id>NCT03298880</nct_id>
  </id_info>
  <brief_title>Testing of a Valsalva Assist Device (VAD) in Healthy Volunteers Performing a Valsalva Manoeuvre</brief_title>
  <official_title>Testing of a Valsalva Assist Device (VAD) to Assess Effects on Vagal Tone and Strain Pressures Achieved Compared to a Standard Manometer in Healthy Volunteers Performing Standard and Modified Valsalva Manoeuvres.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Exeter</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Royal Devon and Exeter NHS Foundation Trust</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Exeter</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      A prototype for a Valsalva Assist Device (VAD), which provides resistance to exhalation, has&#xD;
      been developed and is ready for testing in healthy volunteers. There is a need to ensure the&#xD;
      device can deliver the required strain and evaluate the physiological response (lowered heart&#xD;
      rate) when used to deliver a Valsalva manoeuvre (VM) with and without postural modification.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The aim of this study is to evaluate the performance of a novel Valsalva assist device (VAD)&#xD;
      in healthy volunteer and to confirm the physiological effects of a modified VM.&#xD;
&#xD;
      Specific Objectives:&#xD;
&#xD;
      To measure and compare peak strain pressure and duration produced using the device compared&#xD;
      to a standard manometer in supine and modified postures&#xD;
&#xD;
      To evaluate whether there is a difference in vagal tone (drop in heart rate) in healthy&#xD;
      volunteers performing a VM using the VAD versus manometer.&#xD;
&#xD;
      To evaluate whether there is a difference in vagal tone (drop in heart rate) in healthy&#xD;
      volunteers performing a modified VM versus a standard supine VM using the VAD.&#xD;
&#xD;
      To evaluate whether there is a difference in vagal tone (drop in heart rate) in healthy&#xD;
      volunteers performing a modified VM versus a standard supine VM using a manometer.&#xD;
&#xD;
      The investigators will conduct a single centre repeated measures observational study of use&#xD;
      of the device to generate a Valsalva strain in a sample of healthy adult volunteers from the&#xD;
      University of Exeter or RD&amp;E Hospital staff. All participants will be screened for&#xD;
      eligibility and undergo informed written consent prior to participation. If participants fail&#xD;
      screening due to abnormal clinical readings or vital signs, the chief investigator will&#xD;
      review them, any urgent abnormalities (very unlikely) would be reviewed by the chief&#xD;
      investigator or delegated emergency department doctor as soon as they are discovered.&#xD;
      Depending on the severity, if treatment is required urgently then they will be treated in the&#xD;
      emergency department. Otherwise, they will be referred back to their GP. Potential&#xD;
      participants will be given written information about the study at least 24 hours prior to&#xD;
      recruitment and interested individuals invited to attend screening, recruitment and testing.&#xD;
&#xD;
      Potential participants will be invited to express an interest in taking part by responding to&#xD;
      the trial poster. These posters will be displayed in the medical student common rooms ED&#xD;
      department notice board. The potential participant contacts the researcher leading the&#xD;
      practical aspects of the trial by phone or email. Respondents will be asked how they would&#xD;
      like to receive further information (post, email, and phone) and offered an appointment at&#xD;
      the Clinical Research Facility (CRF) for screening and written consent if eligible, at their&#xD;
      convenience but at least 24 hours after receiving the information sheet. Given the simple,&#xD;
      safe and quick nature of the interventions, participants will be given the choice to take&#xD;
      part after written consent or to return on another date, whichever they would prefer, to&#xD;
      ensure minimal visits whilst giving participants further time to consider taking part should&#xD;
      they wish.&#xD;
&#xD;
      The VM is an extremely safe, physiological manoeuvre which is used in everyday life (eg&#xD;
      straining at stool) and has been used in trial conditions and clinical practice many&#xD;
      thousands of times with no serious adverse events. The investigators will exclude&#xD;
      participants who could conceivably be at any risk of harm from performing a VM or from the&#xD;
      use of the device.&#xD;
&#xD;
      The screening will include 12 lead ECG and physical examination including observations of&#xD;
      heart rate, oxygen saturations, respiratory rate and blood pressure. Any participants with&#xD;
      any detected abnormalities, whether they are excluded from participation or not, will be&#xD;
      informed and referred to their primary care physician as appropriate. All testing will be&#xD;
      conducted in the clinical research facility (CRF) of the Royal Devon &amp; Exeter Hospital,&#xD;
      according to a strict trial protocol.&#xD;
&#xD;
      Test Valsalva Manoeuvres:&#xD;
&#xD;
      Participants will undergo a total of 4 VMs of the following 4 variations in random order,&#xD;
      stratified by method of strain generation to ensure balance between the order of manometer&#xD;
      and device use:&#xD;
&#xD;
        1. Supine VM using a manometer. Supine Valsalva strain using a manometer visible to the&#xD;
           participant with a target of 40mmHg for 15 seconds&#xD;
&#xD;
        2. Supine VM using the device. Supine Valsalva strain using the device connected to&#xD;
           manometer invisible to the participant but visible to a researcher for 15 seconds&#xD;
&#xD;
        3. Modified VM using a manometer. Semi-recumbent (at 45 degrees) Valsalva stain using a&#xD;
           manometer visible to the participant with a target of 40mmHg for 15 seconds followed by&#xD;
           supine positioning and passive 45-degree leg lift immediately at the end of the strain&#xD;
           for a further 15 seconds (the modified VM)&#xD;
&#xD;
        4. Modified VM using the device. Semi-recumbent (at 45 degrees) Valsalva strain using the&#xD;
           device connected to manometer invisible to the participant but visible to a researcher&#xD;
           for 15 seconds followed by supine positioning and passive 45-degree leg lift immediately&#xD;
           at the end of the strain for a further 15 seconds (the modified VM)&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 1, 2017</start_date>
  <completion_date type="Actual">February 5, 2018</completion_date>
  <primary_completion_date type="Actual">February 5, 2018</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Sequential Assignment</intervention_model>
    <intervention_model_description>Four repeated measures in each participant in random order</intervention_model_description>
    <primary_purpose>Other</primary_purpose>
    <masking>None (Open Label)</masking>
    <masking_description>Participants will not be able see manometer when using VAD Analysis of ECG traces will be blind to intervention as traces will be marked with a code, interventions carried out in random order and analysed in batches</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Assessing Heart Rate During the Supine and Modified VM and Assessing Heart Rate While Using the VAD and Manometer</measure>
    <time_frame>3 minutes (4 repetitions of 45 seconds)</time_frame>
    <description>Assessing the effects on heart rate of a supine valsalva manoeuvre compared to the modified Valsalva manoeuvres in healthy volunteers.The investigators will measure the longest RR (length between each r wave) length in mm during the 15 seconds during the manoeuvre and the 15 seconds afterwards on an 3 lead ECG trace. The investigators will measure pre strain heart rate using the 15 seconds of baseline heart rate before the maneouvre on the 3 lead ECG. Using an average of the RR length(mm). The heart rate in beats per minute will then be worked out using a calculation from the RR length. RR length (mm) x0.04 = RR in seconds. (10/RR in seconds)x60 = beats per minute. These arms are combined so as to make the data easier to understand. The higher the number the better the outcome. maximum score is minimum score is 25.9 with maximum 33.6</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants Who Acheived a 15 Second Strain Duration During a VM Comparing a Valsalva Assist Device and a Standard Manometer</measure>
    <time_frame>1 minute (4 repetitions of 15 seconds)</time_frame>
    <description>The investigators measured the time each Valsalva manoeuvre managed to keep to a 15-second drain if they managed 15 seconds at a pressure of 35-45mmHg this would count as an achieved strain.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Peak Sustained Pressure Testing of a Valsalva Assist Device (VAD) Compared to the Standard Manometer</measure>
    <time_frame>15 seconds (4 repetitions of 15 seconds)</time_frame>
    <description>The investigators will measure the highest pressure achieved for more than a second using a manometer in mmHg and compare these done with the VAD and the manometer</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">75</enrollment>
  <condition>SVT</condition>
  <condition>Vagal Bradycardia</condition>
  <arm_group>
    <arm_group_label>Four VM's</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Healthy volunteers undergo repeated VM's - Device: Supine VM VAD, Supine VAD manometer Modified VM VAD, Modified VM Manonmeter</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Supine VM VAD</intervention_name>
    <description>Valsalva strain delivered using VAD</description>
    <arm_group_label>Four VM's</arm_group_label>
    <other_name>Valsalva Assist Device supine</other_name>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Supine VAD manometer</intervention_name>
    <description>supine Valsalva strain delivered using manometer</description>
    <arm_group_label>Four VM's</arm_group_label>
    <other_name>Valsalva Assist Device</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Modified VM VAD</intervention_name>
    <description>modified VM using VAD</description>
    <arm_group_label>Four VM's</arm_group_label>
    <other_name>Standard (supine) position</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Modified VM Manonmeter</intervention_name>
    <description>Postural modified position VM using manometer</description>
    <arm_group_label>Four VM's</arm_group_label>
    <other_name>Modified VM position</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Adult Volunteers between 18 and 60 years old from University of Exeter or RD&amp;E&#xD;
             Hospital staff&#xD;
&#xD;
          -  Sinus rhythm on initial ECG&#xD;
&#xD;
          -  Self-reported good health&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Any regular medication other than the oral contraceptive&#xD;
&#xD;
          -  Previous cardiovascular or respiratory disease&#xD;
&#xD;
          -  Any contraindication to performing a VM strain. (Eg. Known aortic stenosis, recent&#xD;
             myocardial infarction, glaucoma, retinopathy)&#xD;
&#xD;
          -  Pregnancy&#xD;
&#xD;
          -  Any ECG abnormality&#xD;
&#xD;
          -  Any contra-indication to postural modification (any reason the participant can't lie&#xD;
             flat and have both legs lifted to 45 degrees, eg prosthetic hip&#xD;
&#xD;
          -  Inability or refusal to give written consent to take part&#xD;
&#xD;
          -  Observations of heart rate, oxygen saturations, respiratory rate or blood pressure&#xD;
             outside the normal range. Specifically blood pressure less than 100 systolic&#xD;
&#xD;
          -  Caffeinated drinks within 6 hours prior to testing&#xD;
&#xD;
          -  The use of stimulant drugs or alcohol within 24 hours prior to testing&#xD;
      </textblock>
    </criteria>
    <gender>All</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>Andrew Appelboam, MBBS</last_name>
    <role>Principal Investigator</role>
    <affiliation>Royal Devon &amp; Exeter Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Royal Devon &amp; Exeter NHS FT</name>
      <address>
        <city>Exeter</city>
        <state>Devon</state>
        <zip>EX4 7DW</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>June 2021</verification_date>
  <study_first_submitted>September 8, 2017</study_first_submitted>
  <study_first_submitted_qc>September 26, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">October 2, 2017</study_first_posted>
  <results_first_submitted>June 12, 2019</results_first_submitted>
  <results_first_submitted_qc>June 9, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">June 10, 2021</results_first_posted>
  <last_update_submitted>June 9, 2021</last_update_submitted>
  <last_update_submitted_qc>June 9, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">June 10, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Valsalva manoeuvre</keyword>
  <keyword>Vagal tone</keyword>
  <keyword>Modified Valsalva</keyword>
  <keyword>Valsalva Assist Device</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Bradycardia</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>August 24, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/80/NCT03298880/Prot_SAP_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Informed Consent Form</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>November 1, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/80/NCT03298880/ICF_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Four VM's</title>
          <description>Healthy volunteers undergo repeated VM's - Device: Supine VM VAD, Supine VAD manometer Modified VM VAD, Modified VM Manonmeter&#xD;
Supine VM VAD: Valsalva strain delivered using VAD&#xD;
Supine VAD manometer: supine Valsalva strain delivered using manometer&#xD;
Modified VM VAD: modified VM using VAD&#xD;
Modified VM Manonmeter: Postural modified position VM using manometer</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="75"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="75"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Four VM's</title>
          <description>Healthy volunteers undergo repeated VM's - Device: Supine VM VAD, Supine VAD manometer Modified VM VAD, Modified VM Manonmeter&#xD;
Supine VM VAD: Valsalva strain delivered using VAD&#xD;
Supine VAD manometer: supine Valsalva strain delivered using manometer&#xD;
Modified VM VAD: modified VM using VAD&#xD;
Modified VM Manonmeter: Postural modified position VM using manometer</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="75"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="75"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="75"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="75"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="26.19" lower_limit="19" upper_limit="55"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="75"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="45"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="30"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race and Ethnicity Not Collected</title>
          <population>Race and Ethnicity were not collected from any participant.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United Kingdom</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="75"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="75"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Assessing Heart Rate During the Supine and Modified VM and Assessing Heart Rate While Using the VAD and Manometer</title>
        <description>Assessing the effects on heart rate of a supine valsalva manoeuvre compared to the modified Valsalva manoeuvres in healthy volunteers.The investigators will measure the longest RR (length between each r wave) length in mm during the 15 seconds during the manoeuvre and the 15 seconds afterwards on an 3 lead ECG trace. The investigators will measure pre strain heart rate using the 15 seconds of baseline heart rate before the maneouvre on the 3 lead ECG. Using an average of the RR length(mm). The heart rate in beats per minute will then be worked out using a calculation from the RR length. RR length (mm) x0.04 = RR in seconds. (10/RR in seconds)x60 = beats per minute. These arms are combined so as to make the data easier to understand. The higher the number the better the outcome. maximum score is minimum score is 25.9 with maximum 33.6</description>
        <time_frame>3 minutes (4 repetitions of 45 seconds)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Mean Drop in Heart Rate Using the Modified VM</title>
            <description>This measures the mean drop in heart rate before and after the modified valsalva manoeuvre using both the VAD and monometer</description>
          </group>
          <group group_id="O2">
            <title>Mean Drop in Heart Rate of Supine VM</title>
            <description>This measures the mean drop in heart rate before and after the supine valsalva manouevre using the both the VAD and monometer</description>
          </group>
          <group group_id="O3">
            <title>Mean Drop in Heart Rate Using VAD</title>
            <description>This measures the mean drop in heart rate before and after healthy participants undertook the modified and supine Valsalva manoeuvres while using the VAD</description>
          </group>
          <group group_id="O4">
            <title>Mean Drop in Heart Rate From Using the Manometer</title>
            <description>This measures the mean drop in heart rate before and after healthy participants undertook the modified and supine Valsalva manoeuvres while using the manometer</description>
          </group>
        </group_list>
        <measure>
          <title>Assessing Heart Rate During the Supine and Modified VM and Assessing Heart Rate While Using the VAD and Manometer</title>
          <description>Assessing the effects on heart rate of a supine valsalva manoeuvre compared to the modified Valsalva manoeuvres in healthy volunteers.The investigators will measure the longest RR (length between each r wave) length in mm during the 15 seconds during the manoeuvre and the 15 seconds afterwards on an 3 lead ECG trace. The investigators will measure pre strain heart rate using the 15 seconds of baseline heart rate before the maneouvre on the 3 lead ECG. Using an average of the RR length(mm). The heart rate in beats per minute will then be worked out using a calculation from the RR length. RR length (mm) x0.04 = RR in seconds. (10/RR in seconds)x60 = beats per minute. These arms are combined so as to make the data easier to understand. The higher the number the better the outcome. maximum score is minimum score is 25.9 with maximum 33.6</description>
          <units>beat per minute</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="75"/>
                <count group_id="O2" value="75"/>
                <count group_id="O3" value="75"/>
                <count group_id="O4" value="75"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="33.6" lower_limit="6.3" upper_limit="70.2"/>
                    <measurement group_id="O2" value="25.9" lower_limit="5.4" upper_limit="61.2"/>
                    <measurement group_id="O3" value="28.7" lower_limit="8.2" upper_limit="70.2"/>
                    <measurement group_id="O4" value="30.8" lower_limit="5.4" upper_limit="61.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt;0.001</p_value>
            <method>mixed linear regression</method>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>3.7</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>1.12</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>2.1</ci_lower_limit>
            <ci_upper_limit>5.3</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.003</p_value>
            <method>mixed linear regression</method>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>2.3</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.8</ci_lower_limit>
            <ci_upper_limit>3.8</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants Who Acheived a 15 Second Strain Duration During a VM Comparing a Valsalva Assist Device and a Standard Manometer</title>
        <description>The investigators measured the time each Valsalva manoeuvre managed to keep to a 15-second drain if they managed 15 seconds at a pressure of 35-45mmHg this would count as an achieved strain.</description>
        <time_frame>1 minute (4 repetitions of 15 seconds)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>% Who Achieved 15 Second Strain Using a VAD</title>
            <description>percentage of participants utilising the Valsalva assist device to achieve a valsalva manoeuvre who achieved the full 15 second strain using the Valsalva assist device</description>
          </group>
          <group group_id="O2">
            <title>% Who Achieved 15 Second Strain Using a Manometer</title>
            <description>percentage of participants utilising the manometer to achieve a valsalva manoeuvre who achieved the full 15 second strain using the manometer</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants Who Acheived a 15 Second Strain Duration During a VM Comparing a Valsalva Assist Device and a Standard Manometer</title>
          <description>The investigators measured the time each Valsalva manoeuvre managed to keep to a 15-second drain if they managed 15 seconds at a pressure of 35-45mmHg this would count as an achieved strain.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="75"/>
                <count group_id="O2" value="75"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="56"/>
                    <measurement group_id="O2" value="73"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Peak Sustained Pressure Testing of a Valsalva Assist Device (VAD) Compared to the Standard Manometer</title>
        <description>The investigators will measure the highest pressure achieved for more than a second using a manometer in mmHg and compare these done with the VAD and the manometer</description>
        <time_frame>15 seconds (4 repetitions of 15 seconds)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Peak Pressures Acheived by VAD</title>
            <description>peak pressure acheived by VAD</description>
          </group>
          <group group_id="O2">
            <title>Peak Pressures Acheived by Manometer</title>
            <description>Peak pressures achieved by manometer</description>
          </group>
        </group_list>
        <measure>
          <title>Peak Sustained Pressure Testing of a Valsalva Assist Device (VAD) Compared to the Standard Manometer</title>
          <description>The investigators will measure the highest pressure achieved for more than a second using a manometer in mmHg and compare these done with the VAD and the manometer</description>
          <units>mean (mmHg) of peak pressures acheived</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="75"/>
                <count group_id="O2" value="75"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="42.46" lower_limit="30" upper_limit="50"/>
                    <measurement group_id="O2" value="39.96" lower_limit="25" upper_limit="50"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>15 minutes as each patient was taking part</time_frame>
      <desc>this was a very low risk study</desc>
      <group_list>
        <group group_id="E1">
          <title>Four VM's</title>
          <description>Healthy volunteers undergo repeated VM's - Device: Supine VM VAD, Supine VAD manometer Modified VM VAD, Modified VM Manonmeter&#xD;
Supine VM VAD: Valsalva strain delivered using VAD&#xD;
Supine VAD manometer: supine Valsalva strain delivered using manometer&#xD;
Modified VM VAD: modified VM using VAD&#xD;
Modified VM Manonmeter: Postural modified position VM using manometer</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="75"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="75"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="17" subjects_at_risk="75"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>headache</sub_title>
                <counts group_id="E1" subjects_affected="17" subjects_at_risk="75"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Dr Andrew Appelboam, Isabel FitzGerald</name_or_title>
      <organization>University of Exeter, Royal Devon and Exeter Hospital</organization>
      <phone>07515688294</phone>
      <email>andy.appelboam@nhs.net ; if223@exeter.ac.uk</email>
    </point_of_contact>
  </clinical_results>
</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/NCT03298880
org study id: 1617/043
nct id: NCT03298880
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
A prototype for a Valsalva Assist Device (VAD), which provides resistance to exhalation, has
      been developed and is ready for testing in healthy volunteers. There is a need to ensure the
      device can deliver the required strain and evaluate the physiological response (lowered heart
      rate) when used to deliver a Valsalva manoeuvre (VM) with and without postural modification.
The aim of this study is to evaluate the performance of a novel Valsalva assist device (VAD)
      in healthy volunteer and to confirm the physiological effects of a modified VM.

      Specific Objectives:

      To measure and compare peak strain pressure and duration produced using the device compared
      to a standard manometer in supine and modified postures

      To evaluate whether there is a difference in vagal tone (drop in heart rate) in healthy
      volunteers performing a VM using the VAD versus manometer.

      To evaluate whether there is a difference in vagal tone (drop in heart rate) in healthy
      volunteers performing a modified VM versus a standard supine VM using the VAD.

      To evaluate whether there is a difference in vagal tone (drop in heart rate) in healthy
      volunteers performing a modified VM versus a standard supine VM using a manometer.

      The investigators will conduct a single centre repeated measures observational study of use
      of the device to generate a Valsalva strain in a sample of healthy adult volunteers from the
      University of Exeter or RD&E Hospital staff. All participants will be screened for
      eligibility and undergo informed written consent prior to participation. If participants fail
      screening due to abnormal clinical readings or vital signs, the chief investigator will
      review them, any urgent abnormalities (very unlikely) would be reviewed by the chief
      investigator or delegated emergency department doctor as soon as they are discovered.
      Depending on the severity, if treatment is required urgently then they will be treated in the
      emergency department. Otherwise, they will be referred back to their GP. Potential
      participants will be given written information about the study at least 24 hours prior to
      recruitment and interested individuals invited to attend screening, recruitment and testing.

      Potential participants will be invited to express an interest in taking part by responding to
      the trial poster. These posters will be displayed in the medical student common rooms ED
      department notice board. The potential participant contacts the researcher leading the
      practical aspects of the trial by phone or email. Respondents will be asked how they would
      like to receive further information (post, email, and phone) and offered an appointment at
      the Clinical Research Facility (CRF) for screening and written consent if eligible, at their
      convenience but at least 24 hours after receiving the information sheet. Given the simple,
      safe and quick nature of the interventions, participants will be given the choice to take
      part after written consent or to return on another date, whichever they would prefer, to
      ensure minimal visits whilst giving participants further time to consider taking part should
      they wish.

      The VM is an extremely safe, physiological manoeuvre which is used in everyday life (eg
      straining at stool) and has been used in trial conditions and clinical practice many
      thousands of times with no serious adverse events. The investigators will exclude
      participants who could conceivably be at any risk of harm from performing a VM or from the
      use of the device.

      The screening will include 12 lead ECG and physical examination including observations of
      heart rate, oxygen saturations, respiratory rate and blood pressure. Any participants with
      any detected abnormalities, whether they are excluded from participation or not, will be
      informed and referred to their primary care physician as appropriate. All testing will be
      conducted in the clinical research facility (CRF) of the Royal Devon & Exeter Hospital,
      according to a strict trial protocol.

      Test Valsalva Manoeuvres:

      Participants will undergo a total of 4 VMs of the following 4 variations in random order,
      stratified by method of strain generation to ensure balance between the order of manometer
      and device use:

        1. Supine VM using a manometer. Supine Valsalva strain using a manometer visible to the
           participant with a target of 40mmHg for 15 seconds

        2. Supine VM using the device. Supine Valsalva strain using the device connected to
           manometer invisible to the participant but visible to a researcher for 15 seconds

        3. Modified VM using a manometer. Semi-recumbent (at 45 degrees) Valsalva stain using a
           manometer visible to the participant with a target of 40mmHg for 15 seconds followed by
           supine positioning and passive 45-degree leg lift immediately at the end of the strain
           for a further 15 seconds (the modified VM)

        4. Modified VM using the device. Semi-recumbent (at 45 degrees) Valsalva strain using the
           device connected to manometer invisible to the participant but visible to a researcher
           for 15 seconds followed by supine positioning and passive 45-degree leg lift immediately
           at the end of the strain for a further 15 seconds (the modified VM)
allocation: N/A
intervention model: Sequential Assignment
intervention model description: Four repeated measures in each participant in random order
primary purpose: Other
masking: None (Open Label)
masking description: Participants will not be able see manometer when using VAD Analysis of ECG traces will be blind to intervention as traces will be marked with a code, interventions carried out in random order and analysed in batches
measure: Assessing Heart Rate During the Supine and Modified VM and Assessing Heart Rate While Using the VAD and Manometer
time frame: 3 minutes (4 repetitions of 45 seconds)
description: Assessing the effects on heart rate of a supine valsalva manoeuvre compared to the modified Valsalva manoeuvres in healthy volunteers.The investigators will measure the longest RR (length between each r wave) length in mm during the 15 seconds during the manoeuvre and the 15 seconds afterwards on an 3 lead ECG trace. The investigators will measure pre strain heart rate using the 15 seconds of baseline heart rate before the maneouvre on the 3 lead ECG. Using an average of the RR length(mm). The heart rate in beats per minute will then be worked out using a calculation from the RR length. RR length (mm) x0.04 = RR in seconds. (10/RR in seconds)x60 = beats per minute. These arms are combined so as to make the data easier to understand. The higher the number the better the outcome. maximum score is minimum score is 25.9 with maximum 33.6
measure: Percentage of Participants Who Acheived a 15 Second Strain Duration During a VM Comparing a Valsalva Assist Device and a Standard Manometer
time frame: 1 minute (4 repetitions of 15 seconds)
description: The investigators measured the time each Valsalva manoeuvre managed to keep to a 15-second drain if they managed 15 seconds at a pressure of 35-45mmHg this would count as an achieved strain.
measure: Peak Sustained Pressure Testing of a Valsalva Assist Device (VAD) Compared to the Standard Manometer
time frame: 15 seconds (4 repetitions of 15 seconds)
description: The investigators will measure the highest pressure achieved for more than a second using a manometer in mmHg and compare these done with the VAD and the manometer
arm group label: Four VM's
arm group type: Other
description: Healthy volunteers undergo repeated VM's - Device: Supine VM VAD, Supine VAD manometer Modified VM VAD, Modified VM Manonmeter
intervention type: Device
intervention name: Supine VM VAD
description: Valsalva strain delivered using VAD
arm group label: Four VM's
other name: Valsalva Assist Device supine
intervention type: Device
intervention name: Supine VAD manometer
description: supine Valsalva strain delivered using manometer
arm group label: Four VM's
other name: Valsalva Assist Device
intervention type: Other
intervention name: Modified VM VAD
description: modified VM using VAD
arm group label: Four VM's
other name: Standard (supine) position
intervention type: Other
intervention name: Modified VM Manonmeter
description: Postural modified position VM using manometer
arm group label: Four VM's
other name: Modified VM position
criteria: 
gender: All
minimum age: 18 Years
maximum age: 60 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Andrew Appelboam, MBBS
role: Principal Investigator
affiliation: Royal Devon & Exeter Hospital
facility: 
country: United Kingdom
responsible party type: Sponsor
mesh term: Bradycardia
sharing ipd: No
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 