<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/NCT04467879</url>
  </required_header>
  <id_info>
    <org_study_id>001</org_study_id>
    <nct_id>NCT04467879</nct_id>
  </id_info>
  <brief_title>A Pivotal Study To Evaluate The Effectiveness of Isometric Handgrip Therapy In Prehypertensive And Hypertensive Patients</brief_title>
  <official_title>A Pivotal Study To Evaluate The Effectiveness of Isometric Handgrip Therapy In Prehypertensive And Hypertensive Patients</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Zona Health, Inc</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Research &amp; Development Concierge Company</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Zona Health, Inc</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>Yes</is_fda_regulated_device>
    <is_unapproved_device>Yes</is_unapproved_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a double-blind, sham-controlled clinical trial assessing the effectiveness of&#xD;
      personalized isometric handgrip device therapy. Approximately 230 patients who present with a&#xD;
      Systolic Blood Pressure reading of ≤ 149mmHg and who have not taken any antihypertensive&#xD;
      medication for more than 30 days will be enrolled.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study is designed to examine the effectiveness of individualized isometric handgrip&#xD;
      device therapy in prehypertension or hypertension patient subjects who are not at target BP&#xD;
      and who are naive to anti-hypertensive medication for at least 30 days before screening. The&#xD;
      investigational plan examines changes in blood pressure (BP) in up to 230 patient subjects&#xD;
      who are randomized to either the &quot;active&quot; (i.e., the Zona Plus device proposed for&#xD;
      marketing), or to a &quot;sham&quot; device (which is intentionally calibrated for a &quot;weaker grip&quot;).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    New Protocol and Outcome Measures in Review&#xD;
  </why_stopped>
  <start_date type="Actual">June 1, 2020</start_date>
  <completion_date type="Actual">September 14, 2022</completion_date>
  <primary_completion_date type="Actual">September 13, 2022</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <intervention_model_description>Prospective, double-blinded, randomized, sham-controlled study</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
    <masking_description>Double Blinded</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Change from Baseline in Systolic Blood Pressure to Day 70 ± 2 Days</measure>
    <time_frame>Change from Baseline to Day 70 ±2 Days</time_frame>
    <description>Comparative assessment in the change from Baseline in seated cuff Systolic Blood Pressure after ten(10) weeks of treatment between patients treated with the Zona Plus nominal device (&quot;stronger grip&quot;) and patients treated with the Placebo control device (&quot;weaker grip&quot;). A reduction in Systolic Blood ≥ 5 Preassure after 10 weeks of treatment is considered to be a better outcome.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change from Baseline in Diastolic Blood Pressure to Day 70 ± 2 Days</measure>
    <time_frame>Change from Baseline to Day 70 ±2 Days</time_frame>
    <description>Comparative assessment of the change from Baseline in seated cuff Diastolic Blood Pressure after 10 weeks of treatment between patients treated with the Zona Plus nominal device (&quot;stronger grip&quot;) and patients treated with the Placebo control device (&quot;weaker grip&quot;).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage change from Baseline in Systolic Blood Pressure reduction at Day 70 ± 2 Days</measure>
    <time_frame>Change from Baseline to Day 70 ± 2 Days</time_frame>
    <description>Comparative assessment in the percentage of patients who achieve a clinically significant Systolic Blood Pressure reduction (defined as ≥ 5 mmHg) at Day 70 ± 2 Days.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage change from Baseline in Diastolic Blood Pressure reduction at Day 70 ± 2 Days</measure>
    <time_frame>Change from Baseline to Day 70 ± 2 Days</time_frame>
    <description>Comparative assessment in the percentage of patients who achieve a clinically significant Diastolic Blood Pressure reduction (defined as ≥3 mmHg) at Day 70 ± 2 Days.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage change from Baseline in Systolic Blood Pressure reduction at Day 160 ± 4 Days</measure>
    <time_frame>Change from Baseline to Day 160 ± 4 Days</time_frame>
    <description>Comparative assessment in change from Baseline in the seated cuff Systolic Blood Pressure after 6 months Day 160 ± 4 of treatment between patients treated with the Zona Plus nominal device and patients treated with the Placebo control device.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage change in Diastolic Blood Pressure reduction at Day 160 ± 4 Days</measure>
    <time_frame>Change from Baseline to Day 160 ± 4 Days</time_frame>
    <description>Comparative assessment in change from Baseline in the seated cuff Diastolic Blood Pressure after 6 months Day 160 ± 4 Days of treatment between patients treated with the Zona Plus nominal device and patients treated with the Placebo control device.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage change from Baseline in Systolic Blood Pressure reduction at Day 160 ± 4 Days</measure>
    <time_frame>Change from Baseline to Day 160 ± 4 Days</time_frame>
    <description>Comparative assessment in the percentage of patients who achieve a clinically significant Systolic Blood Pressure reduction (defined as ≥ 5 mmHg) at Day 160 ± 4 Days</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage change in Diastolic Blood Pressure reduction at Day 160 ± 4 Days</measure>
    <time_frame>Change from Baseline to Day 160 ± 4 Days</time_frame>
    <description>Comparative assessment in the percentage of patients who achieve a clinically significant Diastolic Blood Pressure reduction defined as ≥3 mmHg at Day 160 ± 4 Days</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Comparison of Heart Rate between Zona Plus nominal device and Placebo controlled device</measure>
    <time_frame>Change from Baseline to Day 160 ± 4 Days</time_frame>
    <description>The Heart Rate (HR) will be recorded and compared between the Zona Plus nominal device and the Placebo control device treatment groups.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">146</enrollment>
  <condition>Hypertension, Systolic</condition>
  <arm_group>
    <arm_group_label>Zona Plus - Active - &quot;Normal Grip&quot;</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Using the Zona Plus Device, the patient will perform a twelve-minute isometric handgrip therapy session at approximately the same time each day . After an initial handgrip strength assessment (the session calibration), a two-minute isometric routine is performed four times, two sessions per hand, with a one-minute non-grip, or rest session between each isometric routine.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control Device - Sham - &quot;Weaker Grip&quot;</arm_group_label>
    <arm_group_type>Sham Comparator</arm_group_type>
    <description>Using the Zona Sham Control Device the patient will perform a twelve-minute isometric handgrip therapy session at approximately the same time each day. After an initial handgrip strength assessment (the calibration), a two-minute isometric routine is performed four times, two sessions per hand, with a one-minute non-grip, or rest session between each isometric routine.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Zona Plus Device</intervention_name>
    <description>Zona Plus 3.0 Individualized Isometric Handgrip Therapy Device</description>
    <arm_group_label>Zona Plus - Active - &quot;Normal Grip&quot;</arm_group_label>
    <other_name>Zona Plus 3.0</other_name>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Control Device</intervention_name>
    <description>Zona Plus control sham device, with a nominal weaker grip</description>
    <arm_group_label>Control Device - Sham - &quot;Weaker Grip&quot;</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria&#xD;
&#xD;
          -  Male or female of any ethnicity between 18 and 80 years of age&#xD;
&#xD;
          -  Diagnosed with prehypertension or hypertension and verified during the Baseline visit&#xD;
&#xD;
          -  Non-use of antihypertensive medication for ≥30 prior to screening&#xD;
&#xD;
          -  Currently not taking any antihypertensive medications or decline to take any&#xD;
             antihypertensive medications(e.g., diuretic, angiotensin-converting enzyme inhibitor&#xD;
             (ACEI), angiotensin II receptor blocker (ARB), ] beta-blocker (BB), renin inhibitor&#xD;
             (RI), calcium channel blocker (CCB) or alpha-adrenergic agonist (clonidine))&#xD;
&#xD;
          -  Sufficient vision with the patient able to see the screen prompts on the device,&#xD;
             sufficient hearing with the patient able to hear the device audio prompts, sufficient&#xD;
             hand strength (demonstrated by a maximum voluntary contraction equaling 35 units of&#xD;
             force in both hands measured by the device)&#xD;
&#xD;
          -  Baseline Blood Pressure measurements collected and study device training completed&#xD;
             during the Baseline visit&#xD;
&#xD;
          -  Non-use of medications and over the counter (OTC)supplement regimen related to&#xD;
             hypertension throughout the study duration&#xD;
&#xD;
          -  Only one patient per household can participate in the study, eliminating the potential&#xD;
             of unblinding&#xD;
&#xD;
          -  Able to comply with study procedures and agrees to complete all required study visits&#xD;
             and associated activities&#xD;
&#xD;
          -  Ability to give written informed consent in either English, Spanish or French •≤149&#xD;
             mmHg, Systolic Blood Pressure wherein patients who present with Systolic Blood&#xD;
             Pressure readings ≥140 mmHg will receive heightened monitoring throughout the first&#xD;
             month of the study&#xD;
&#xD;
        Exclusion Criteria&#xD;
&#xD;
          -  Pregnant or not using adequate contraception&#xD;
&#xD;
          -  Blood Pressure ≥150 mmHg (systolic) and/or &gt;90 mmHg (diastolic)&#xD;
&#xD;
          -  History of heart failure&#xD;
&#xD;
          -  Hospitalization due to a hypertensive emergency, with impending or progressive target&#xD;
             organ dysfunction (i.e., renal dysfunction, left ventricular hypertrophy or CNS&#xD;
             involvement) within the past six (6) months&#xD;
&#xD;
             •&gt;10 mmHg difference in Systolic Blood Pressure between the right and left arms&#xD;
             collected during screening&#xD;
&#xD;
          -  Unstable Blood Pressure, defined as &gt;5 mmHg variance between any two (2) consecutive&#xD;
             weekly readings (with a maximum of four (4) attempts) to determine a baseline BP&#xD;
             measurement&#xD;
&#xD;
          -  Arm circumference greater than 45cm&#xD;
&#xD;
          -  Acute illness, infection, or inflammation&#xD;
&#xD;
          -  Unstable cardiovascular disorder, such as MI, unstable angina, significant arrhythmia,&#xD;
             stroke, or TIA within the last six (6)months, or other serious comorbidity impacting&#xD;
             life expectancy to &lt; than a 1 year&#xD;
&#xD;
          -  Rest or exertional angina pectoris in the previous six (6) months&#xD;
&#xD;
          -  History of solid organ transplant&#xD;
&#xD;
          -  Secondary form of hypertension (HTN) etiology, including but not limited to primary&#xD;
             aldosteronism, chronic steroid therapy and Cushing syndrome, pheochromocytoma, aorta&#xD;
             coarctation or untreated thyroid or parathyroid disease&#xD;
&#xD;
          -  Concurrent participation in an investigational clinical study that has not completed&#xD;
             the follow-up period or planned participation in another study within the next six(6)&#xD;
             months&#xD;
&#xD;
          -  Any condition or personal circumstance that, in the judgment of the investigator,&#xD;
             might interfere with the collection of complete, good quality data or the completion&#xD;
             of the research study&#xD;
&#xD;
          -  Currently own or have owned another Zona Plus device and are,or have been,voluntarily&#xD;
             performing the isometric handgrip activities.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Mark Young</last_name>
    <role>Study Chair</role>
    <affiliation>Zona Health, Inc</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Saint Louis Heart &amp; Vascular, P.C.</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63044</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Carolinas Research Center LLC</name>
      <address>
        <city>Charlotte</city>
        <state>North Carolina</state>
        <zip>28215</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Goldsboro Medical Center</name>
      <address>
        <city>Goldsboro</city>
        <state>North Carolina</state>
        <zip>27534</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sante Clinical Research</name>
      <address>
        <city>Kerrville</city>
        <state>Texas</state>
        <zip>78028</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sun Research Institute</name>
      <address>
        <city>San Antonio</city>
        <state>Texas</state>
        <zip>78215</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
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    <url>http://www.fda.gov/regulatory-information/search-fda-guidance-documents/hypertension-indication-drug-labeling-cardiovascular-outcome-claims</url>
    <description>Drug Labeling for Cardiovascular Outcome Claims</description>
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    <url>http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm073147.pdf</url>
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  <verification_date>September 2022</verification_date>
  <study_first_submitted>July 8, 2020</study_first_submitted>
  <study_first_submitted_qc>July 8, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 13, 2020</study_first_posted>
  <last_update_submitted>September 19, 2022</last_update_submitted>
  <last_update_submitted_qc>September 19, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">September 22, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Diastolic Hypertension</keyword>
  <keyword>HandGrip Therapy</keyword>
  <keyword>Pre-Hypertension</keyword>
  <keyword>Isometric Exercise</keyword>
  <keyword>Vascular Hypertension</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hypertension</mesh_term>
    <mesh_term>Isolated Systolic Hypertension</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>If in the future Investigators want to access the data for secondary analysis they can submit a request from the Sponsor or R&amp;D Data Management Contact. Individual patient data will not be shared by the sponsor directly and will be aggregated, monitored, and de-identified (APD) via 1) final approved clinical study report 2) any manuscripts or summary results report via an email request to the central contact once database lock has occurred and reports are generated.</ipd_description>
  </patient_data>
  <!-- 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/NCT04467879
org study id: 001
nct id: NCT04467879
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: Yes
is unapproved device: Yes
This is a double-blind, sham-controlled clinical trial assessing the effectiveness of
      personalized isometric handgrip device therapy. Approximately 230 patients who present with a
      Systolic Blood Pressure reading of ≤ 149mmHg and who have not taken any antihypertensive
      medication for more than 30 days will be enrolled.
This study is designed to examine the effectiveness of individualized isometric handgrip
      device therapy in prehypertension or hypertension patient subjects who are not at target BP
      and who are naive to anti-hypertensive medication for at least 30 days before screening. The
      investigational plan examines changes in blood pressure (BP) in up to 230 patient subjects
      who are randomized to either the "active" (i.e., the Zona Plus device proposed for
      marketing), or to a "sham" device (which is intentionally calibrated for a "weaker grip").
allocation: Randomized
intervention model: Single Group Assignment
intervention model description: Prospective, double-blinded, randomized, sham-controlled study
primary purpose: Treatment
masking: Double (Participant, Investigator)
masking description: Double Blinded
measure: Change from Baseline in Systolic Blood Pressure to Day 70 ± 2 Days
time frame: Change from Baseline to Day 70 ±2 Days
description: Comparative assessment in the change from Baseline in seated cuff Systolic Blood Pressure after ten(10) weeks of treatment between patients treated with the Zona Plus nominal device ("stronger grip") and patients treated with the Placebo control device ("weaker grip"). A reduction in Systolic Blood ≥ 5 Preassure after 10 weeks of treatment is considered to be a better outcome.
measure: Change from Baseline in Diastolic Blood Pressure to Day 70 ± 2 Days
time frame: Change from Baseline to Day 70 ±2 Days
description: Comparative assessment of the change from Baseline in seated cuff Diastolic Blood Pressure after 10 weeks of treatment between patients treated with the Zona Plus nominal device ("stronger grip") and patients treated with the Placebo control device ("weaker grip").
measure: Percentage change from Baseline in Systolic Blood Pressure reduction at Day 70 ± 2 Days
time frame: Change from Baseline to Day 70 ± 2 Days
description: Comparative assessment in the percentage of patients who achieve a clinically significant Systolic Blood Pressure reduction (defined as ≥ 5 mmHg) at Day 70 ± 2 Days.
measure: Percentage change from Baseline in Diastolic Blood Pressure reduction at Day 70 ± 2 Days
time frame: Change from Baseline to Day 70 ± 2 Days
description: Comparative assessment in the percentage of patients who achieve a clinically significant Diastolic Blood Pressure reduction (defined as ≥3 mmHg) at Day 70 ± 2 Days.
measure: Percentage change from Baseline in Systolic Blood Pressure reduction at Day 160 ± 4 Days
time frame: Change from Baseline to Day 160 ± 4 Days
description: Comparative assessment in change from Baseline in the seated cuff Systolic Blood Pressure after 6 months Day 160 ± 4 of treatment between patients treated with the Zona Plus nominal device and patients treated with the Placebo control device.
measure: Percentage change in Diastolic Blood Pressure reduction at Day 160 ± 4 Days
time frame: Change from Baseline to Day 160 ± 4 Days
description: Comparative assessment in change from Baseline in the seated cuff Diastolic Blood Pressure after 6 months Day 160 ± 4 Days of treatment between patients treated with the Zona Plus nominal device and patients treated with the Placebo control device.
measure: Percentage change from Baseline in Systolic Blood Pressure reduction at Day 160 ± 4 Days
time frame: Change from Baseline to Day 160 ± 4 Days
description: Comparative assessment in the percentage of patients who achieve a clinically significant Systolic Blood Pressure reduction (defined as ≥ 5 mmHg) at Day 160 ± 4 Days
measure: Percentage change in Diastolic Blood Pressure reduction at Day 160 ± 4 Days
time frame: Change from Baseline to Day 160 ± 4 Days
description: Comparative assessment in the percentage of patients who achieve a clinically significant Diastolic Blood Pressure reduction defined as ≥3 mmHg at Day 160 ± 4 Days
measure: Comparison of Heart Rate between Zona Plus nominal device and Placebo controlled device
time frame: Change from Baseline to Day 160 ± 4 Days
description: The Heart Rate (HR) will be recorded and compared between the Zona Plus nominal device and the Placebo control device treatment groups.
arm group label: Zona Plus - Active - "Normal Grip"
arm group type: Experimental
description: Using the Zona Plus Device, the patient will perform a twelve-minute isometric handgrip therapy session at approximately the same time each day . After an initial handgrip strength assessment (the session calibration), a two-minute isometric routine is performed four times, two sessions per hand, with a one-minute non-grip, or rest session between each isometric routine.
arm group label: Control Device - Sham - "Weaker Grip"
arm group type: Sham Comparator
description: Using the Zona Sham Control Device the patient will perform a twelve-minute isometric handgrip therapy session at approximately the same time each day. After an initial handgrip strength assessment (the calibration), a two-minute isometric routine is performed four times, two sessions per hand, with a one-minute non-grip, or rest session between each isometric routine.
intervention type: Device
intervention name: Zona Plus Device
description: Zona Plus 3.0 Individualized Isometric Handgrip Therapy Device
arm group label: Zona Plus - Active - "Normal Grip"
other name: Zona Plus 3.0
intervention type: Device
intervention name: Control Device
description: Zona Plus control sham device, with a nominal weaker grip
arm group label: Control Device - Sham - "Weaker Grip"
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
last name: Mark Young
role: Study Chair
affiliation: Zona Health, Inc
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
url: http://www.fda.gov/regulatory-information/search-fda-guidance-documents/hypertension-indication-drug-labeling-cardiovascular-outcome-claims
description: Drug Labeling for Cardiovascular Outcome Claims
url: http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm073147.pdf
description: Principles for ClinicalEvaluation ofNew Antihypertensive Drugs.
url: http://www.nhlbi.nih.gov/files/docs/guidelines/jnc7full.pdf
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responsible party type: Sponsor
mesh term: Hypertension
mesh term: Isolated Systolic Hypertension
sharing ipd: No
ipd description: If in the future Investigators want to access the data for secondary analysis they can submit a request from the Sponsor or R&D Data Management Contact. Individual patient data will not be shared by the sponsor directly and will be aggregated, monitored, and de-identified (APD) via 1) final approved clinical study report 2) any manuscripts or summary results report via an email request to the central contact once database lock has occurred and reports are generated.