<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/NCT03781739</url>
  </required_header>
  <id_info>
    <org_study_id>IRB # 16-005813</org_study_id>
    <nct_id>NCT03781739</nct_id>
  </id_info>
  <brief_title>MANP in Hypertension and Metabolic Syndrome</brief_title>
  <acronym>MANP-HTN-MS</acronym>
  <official_title>A PHASE I, DOUBLE BLIND, PLACEBO-CONTROLLED STUDY EVALUATING THE CARDIOVASCULAR AND METABOLIC PROPERTIES OF MANP IN SUBJECTS WITH HYPERTENSION AND METABOLIC SYNDROME ACCORDING TO RS5068 GENOTYPES</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Mayo Clinic</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>American Heart Association</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Mayo Clinic</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Evaluate the cardiovascular and metabolic properties of MANP in subjects with HTN and MS&#xD;
      according to rs5068 genotypes&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      6 Study Procedures 6.1 Day 0 - Visit 1 (screening visit) 6.2 At visit 1 informed consent will&#xD;
      be obtained (Table 1). Introduction and orientation to the study will take place. Medical&#xD;
      history will be collected. Physical exam will be performed and laboratory exams history will&#xD;
      be screened. Electrocardiogram will be recorded and screening laboratory tests will be&#xD;
      performed. Blood pressure and heart rate will be recorded. Subjects will be instructed about&#xD;
      the fluid intake allowed (2.5 liter/day) and the diet (moderate sodium intake: 3.0 gr/day) to&#xD;
      follow for the duration of the study from day 1 to day 7. Subjects will be instructed on&#xD;
      completing a 24-hour urine collection starting on day 4 at 4pm (see day 4 below).&#xD;
      Antihypertensive medications are required to be at a stable dose for 30 days preceding visit&#xD;
      1 on day 1. Throughout the duration of the study subjects will be maintained on their chronic&#xD;
      antihypertensive treatment except for day 6 in which MANP or placebo will be administered.&#xD;
      Subjects will be instructed to avoid strenuous physical activities and to abstain from&#xD;
      smoking and alcohol from day 1 until the completion of the study on day 7. Caffeine&#xD;
      consumption will be prohibited from 7.00 pm on day 5 until the dismissal from the CRTU on day&#xD;
      7. Day 1 Start of diet and fluid restriction compliance. (Interval of time between day 0 and&#xD;
      day 1 will depend upon the CRTU schedules 6.3 Day 4 On Day 4 at 4 pm the subjects will start&#xD;
      24-hour urine collection in order to establish adherence to the moderate sodium diet (Table&#xD;
      1).&#xD;
&#xD;
      6.4 Day 5 On day 5 at 4pm subjects will bring the 24-hour urine collection to the CRTU and&#xD;
      24-hour urine sodium will be measured. If the patient has been compliant with the sodium&#xD;
      diet, she/he will be admitted to the CRTU to continue the study and a physical exam will be&#xD;
      performed. At 7.00 pm subjects will start fasting and abstain from their usual hypoglycemic&#xD;
      therapy in consideration of the blood draws for metabolic parameters that will be performed&#xD;
      on day 6. Caffeine consumption is prohibited from 7:00 pm on day 5 until the dismissal from&#xD;
      the CRTU on day 7.&#xD;
&#xD;
      6.5 Day 6 - Visit 2 On day 6 at 8:00 am enrolled patients will receive a single injection of&#xD;
      MANP (2.5 μg/kg SQ) or placebo (0.9% saline solution) and will be under observation for the&#xD;
      24 hours following the MANP/placebo administration (Table 1). Blood pressure and heart rate&#xD;
      will be monitored continually and recorded before MANP/placebo injection and at several&#xD;
      intervals after MANP/placebo administration. Timed urine collection and blood samples to&#xD;
      evaluate neurohumoral, renal function and metabolic plasma parameters will be collected prior&#xD;
      to MANP /placebo injection and at different time points after MANP and placebo&#xD;
      administration. Subjects will eat their meal and take their usual hypoglycemic medications&#xD;
      after the last blood draw for metabolic parameters (4 hours after the MANP injection).&#xD;
      Subjects will be maintained on their chronic antihypertensive treatment except for day 6 in&#xD;
      which MANP will be administered. They will take their usual antihypertensive therapy 24 hours&#xD;
      after MANP injection.&#xD;
&#xD;
      6.6 Day 7 Once completed the 24 hour observation following MANP administration a physical&#xD;
      exam will be performed and the subjects will be dismissed from the CRTU&#xD;
&#xD;
      6.7 Day 14 (± 2 days) Laboratory tests will be performed and assessed. Subjects will be&#xD;
      contacted by phone to review laboratory tests results and assess the onset of any potential&#xD;
      side effect following the MANP/placebo administration.&#xD;
&#xD;
      6.8 Day 30 (-2 days, + 5 days) Blood collection for anti-MANP antibody testing will be&#xD;
      performed.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 18, 2017</start_date>
  <completion_date type="Actual">December 10, 2019</completion_date>
  <primary_completion_date type="Actual">November 14, 2019</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Care Provider, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>cardiovascular outcome</measure>
    <time_frame>24 hours</time_frame>
    <description>systolic blood pressure</description>
  </primary_outcome>
  <primary_outcome>
    <measure>second messenger</measure>
    <time_frame>24 hours</time_frame>
    <description>cGMP plasma levels</description>
  </primary_outcome>
  <primary_outcome>
    <measure>metabolic outcome</measure>
    <time_frame>24 hours</time_frame>
    <description>glycerol and non-esterified fatty acids (NEFA) plasma levels</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>secondary cardiovascular outcome</measure>
    <time_frame>24 hours</time_frame>
    <description>diastolic blood pressure</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>secondary metabolic outcome</measure>
    <time_frame>24 hours</time_frame>
    <description>adiponectin plasma levels</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">22</enrollment>
  <condition>Hypertension</condition>
  <condition>Metabolic Syndrome</condition>
  <arm_group>
    <arm_group_label>MANP</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>subjects receiving MANP (2.5 micrograms/kg, single subcutaneous injection)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>subjects receiving placebo (saline solution, single subcutaneous injection)</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>MANP</intervention_name>
    <description>single subcutaneous injection of MANP and monitoring of metabolic, cardiovascular and renal parameters</description>
    <arm_group_label>MANP</arm_group_label>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Hypertension defined as 140 mmHg ≤ systolic BP ≤ 180 mmHg or 90 mmHg ≤ diastolic BP ≤&#xD;
             100 mmHg despite anti-hypertensive medical therapy&#xD;
&#xD;
          -  Metabolic Syndrome defined as the presence of any two of the following traits:&#xD;
&#xD;
          -  Abdominal obesity, defined as a waist circumference in men ≥102 cm (40 in) and in&#xD;
             women ≥88 cm (35 in)&#xD;
&#xD;
          -  Serum triglycerides ≥150 mg/dL (1.7 mmol/L)&#xD;
&#xD;
          -  Serum HDL cholesterol &lt;40 mg/dL (1 mmol/L) in men and &lt;50 mg/dL (1.3 mmol/L) in women&#xD;
             or drug treatment for low HDL cholesterol&#xD;
&#xD;
          -  Fasting plasma glucose ≥100 mg/dL (5.6 mmol/L) or drug treatment for elevated blood&#xD;
             glucose&#xD;
&#xD;
          -  Between the ages of 18 and 75 years&#xD;
&#xD;
          -  Use of antihypertensive medications at a stable dose for 30 days preceding screening&#xD;
             visit.&#xD;
&#xD;
          -  Use of statins or ezetimibe or combinations on stable dose for 60 days preceding&#xD;
             screening visit.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Known hypersensitivity or allergy to MANP or its components, carperitide, other&#xD;
             natriuretic peptides, or related compounds;&#xD;
&#xD;
          -  Subjects with orthostatic hypotension at the screening visit, defined as a decrease in&#xD;
             systolic BP of &gt;20 mmHg or a decrease in diastolic BP of &gt;10 mmHg within three minutes&#xD;
             of standing when compared with blood pressure from the sitting position.&#xD;
&#xD;
          -  Subjects with a systolic BP &gt;180 mmHg or a diastolic BP &gt;100 mmHg&#xD;
&#xD;
          -  Women of child-bearing potential&#xD;
&#xD;
          -  The presence of abnormal laboratory values at screening visit considered clinically&#xD;
             significant by the Investigator. Specifically they will be excluded if a) Serum sodium&#xD;
             of &lt; 135 mEq/dL or &gt; 145 mEq/dL; b) Serum potassium of &lt; 3.5 mEq/dL or &gt; 5.1 mEq/dL&#xD;
&#xD;
          -  Subjects whose body weight has changed more than 3% in the last 3 months&#xD;
&#xD;
          -  Having received any investigational drug or device within 30 days prior to entry into&#xD;
             the study;&#xD;
&#xD;
          -  A history (within the last 2 years) of alcohol risky use (defined as more than 14&#xD;
             standard drinks per week on average or more than 4 drinks on any day for men under age&#xD;
             65 - defined as more than 7 standard drinks per week on average or more than 3 drinks&#xD;
             on any day for women and adults 65 years and older);&#xD;
&#xD;
          -  A history of illicit drug use, psychiatric illness that might impair the participation&#xD;
             to the study, physical dependence to any opioid, or any history of substance abuse or&#xD;
             addiction;&#xD;
&#xD;
          -  A history of difficulty with donating blood or donated blood or blood products within&#xD;
             45 days prior to enrollment;&#xD;
&#xD;
          -  Clinically significant new illness in the 1 month before screening in the opinion of&#xD;
             the Investigator;&#xD;
&#xD;
          -  History of severe allergies;&#xD;
&#xD;
          -  History of coronary artery disease or cerebrovascular disease or syncope;&#xD;
&#xD;
          -  History of epilepsy or other seizure disorder;&#xD;
&#xD;
          -  History of organ transplantation;&#xD;
&#xD;
          -  Malignancy within 5 years of the screening visit (with the exception of basal cell and&#xD;
             squamous cell skin carcinoma);&#xD;
&#xD;
          -  Clinically significant intrinsic renal disease, renal artery stenosis, or history of&#xD;
             fibromuscular dysplasia of the renal arteries;&#xD;
&#xD;
          -  Consumption of a phosphodiesterase-5 inhibitor (sildenafil, vardenafil, or tadalafil)&#xD;
             within 72 hours of receiving MANP.&#xD;
&#xD;
          -  Episodic or chronic use of nitrates (Isordil, nitroglycerine), MAO inhibitors,&#xD;
             antipsychotics, antiarrhythmics, psychostimulants, systemic corticosteroids,&#xD;
             cholestyramine and cholestipol reisins, fibrates, nicotinic acid, cyclosporin,&#xD;
             rifampin or other highly potent PgP inhibitors.&#xD;
&#xD;
          -  Any disease or condition (medical or surgical) which, in the opinion of the&#xD;
             investigator, might compromise the hematologic, cardiovascular, pulmonary, renal,&#xD;
             gastrointestinal, hepatic, or central nervous system; or other conditions that may&#xD;
             interfere with the absorption, distribution, metabolism or excretion of study drug, or&#xD;
             would place the subject at increased risk.&#xD;
&#xD;
          -  Subjects who smoke or have any history of tobacco product use more recently than 6&#xD;
             months prior to the enrollment into the study&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Paul M McKie, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Mayo Foundation</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Mayo Foundation</name>
      <address>
        <city>Rochester</city>
        <state>Minnesota</state>
        <zip>55905</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>https://www.mayo.edu/research/clinical-trials</url>
    <description>Mayo Clinic Clinical Trials</description>
  </link>
  <verification_date>November 2020</verification_date>
  <study_first_submitted>December 18, 2018</study_first_submitted>
  <study_first_submitted_qc>December 18, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 20, 2018</study_first_posted>
  <last_update_submitted>November 10, 2020</last_update_submitted>
  <last_update_submitted_qc>November 10, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">November 13, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Mayo Clinic</investigator_affiliation>
    <investigator_full_name>Paul M. McKie, M.D.</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hypertension</mesh_term>
    <mesh_term>Metabolic Syndrome</mesh_term>
    <mesh_term>Syndrome</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </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/NCT03781739
org study id: IRB # 16-005813
nct id: NCT03781739
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
Evaluate the cardiovascular and metabolic properties of MANP in subjects with HTN and MS
      according to rs5068 genotypes
6 Study Procedures 6.1 Day 0 - Visit 1 (screening visit) 6.2 At visit 1 informed consent will
      be obtained (Table 1). Introduction and orientation to the study will take place. Medical
      history will be collected. Physical exam will be performed and laboratory exams history will
      be screened. Electrocardiogram will be recorded and screening laboratory tests will be
      performed. Blood pressure and heart rate will be recorded. Subjects will be instructed about
      the fluid intake allowed (2.5 liter/day) and the diet (moderate sodium intake: 3.0 gr/day) to
      follow for the duration of the study from day 1 to day 7. Subjects will be instructed on
      completing a 24-hour urine collection starting on day 4 at 4pm (see day 4 below).
      Antihypertensive medications are required to be at a stable dose for 30 days preceding visit
      1 on day 1. Throughout the duration of the study subjects will be maintained on their chronic
      antihypertensive treatment except for day 6 in which MANP or placebo will be administered.
      Subjects will be instructed to avoid strenuous physical activities and to abstain from
      smoking and alcohol from day 1 until the completion of the study on day 7. Caffeine
      consumption will be prohibited from 7.00 pm on day 5 until the dismissal from the CRTU on day
      7. Day 1 Start of diet and fluid restriction compliance. (Interval of time between day 0 and
      day 1 will depend upon the CRTU schedules 6.3 Day 4 On Day 4 at 4 pm the subjects will start
      24-hour urine collection in order to establish adherence to the moderate sodium diet (Table
      1).

      6.4 Day 5 On day 5 at 4pm subjects will bring the 24-hour urine collection to the CRTU and
      24-hour urine sodium will be measured. If the patient has been compliant with the sodium
      diet, she/he will be admitted to the CRTU to continue the study and a physical exam will be
      performed. At 7.00 pm subjects will start fasting and abstain from their usual hypoglycemic
      therapy in consideration of the blood draws for metabolic parameters that will be performed
      on day 6. Caffeine consumption is prohibited from 7:00 pm on day 5 until the dismissal from
      the CRTU on day 7.

      6.5 Day 6 - Visit 2 On day 6 at 8:00 am enrolled patients will receive a single injection of
      MANP (2.5 μg/kg SQ) or placebo (0.9% saline solution) and will be under observation for the
      24 hours following the MANP/placebo administration (Table 1). Blood pressure and heart rate
      will be monitored continually and recorded before MANP/placebo injection and at several
      intervals after MANP/placebo administration. Timed urine collection and blood samples to
      evaluate neurohumoral, renal function and metabolic plasma parameters will be collected prior
      to MANP /placebo injection and at different time points after MANP and placebo
      administration. Subjects will eat their meal and take their usual hypoglycemic medications
      after the last blood draw for metabolic parameters (4 hours after the MANP injection).
      Subjects will be maintained on their chronic antihypertensive treatment except for day 6 in
      which MANP will be administered. They will take their usual antihypertensive therapy 24 hours
      after MANP injection.

      6.6 Day 7 Once completed the 24 hour observation following MANP administration a physical
      exam will be performed and the subjects will be dismissed from the CRTU

      6.7 Day 14 (± 2 days) Laboratory tests will be performed and assessed. Subjects will be
      contacted by phone to review laboratory tests results and assess the onset of any potential
      side effect following the MANP/placebo administration.

      6.8 Day 30 (-2 days, + 5 days) Blood collection for anti-MANP antibody testing will be
      performed.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Investigator)
measure: cardiovascular outcome
time frame: 24 hours
description: systolic blood pressure
measure: second messenger
time frame: 24 hours
description: cGMP plasma levels
measure: metabolic outcome
time frame: 24 hours
description: glycerol and non-esterified fatty acids (NEFA) plasma levels
measure: secondary cardiovascular outcome
time frame: 24 hours
description: diastolic blood pressure
measure: secondary metabolic outcome
time frame: 24 hours
description: adiponectin plasma levels
arm group label: MANP
arm group type: Experimental
description: subjects receiving MANP (2.5 micrograms/kg, single subcutaneous injection)
arm group label: Placebo
arm group type: Placebo Comparator
description: subjects receiving placebo (saline solution, single subcutaneous injection)
intervention type: Drug
intervention name: MANP
description: single subcutaneous injection of MANP and monitoring of metabolic, cardiovascular and renal parameters
arm group label: MANP
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Paul M McKie, M.D.
role: Principal Investigator
affiliation: Mayo Foundation
facility: 
country: United States
url: https://www.mayo.edu/research/clinical-trials
description: Mayo Clinic Clinical Trials
responsible party type: Principal Investigator
investigator affiliation: Mayo Clinic
investigator full name: Paul M. McKie, M.D.
investigator title: Principal Investigator
mesh term: Hypertension
mesh term: Metabolic Syndrome
mesh term: Syndrome
sharing ipd: No