<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/NCT03251287</url>
  </required_header>
  <id_info>
    <org_study_id>201323</org_study_id>
    <nct_id>NCT03251287</nct_id>
  </id_info>
  <brief_title>Nitrite in Hypertrophic Cardiomyopathy (HCM) Study</brief_title>
  <official_title>Mechanistic Study of the Effect of Inorganic Sodium Nitrate on Cardiac and Skeletal Muscle Metabolic Efficiency in Patients With Hypertrophic Cardiomyopathy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of East Anglia</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Norfolk and Norwich University Hospitals NHS Foundation Trust</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>British Medical Research Council</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of East Anglia</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>
      Inorganic nitrate, which is found at high levels in green leafy vegetables, is reduced to&#xD;
      nitrite by bacteria in the mouth, swallowed, and absorbed in the stomach into the blood.&#xD;
      Studies have shown that increasing the blood levels of nitrite improves the way that muscles&#xD;
      use oxygen and energy during exercise, and potentially blood flow.&#xD;
&#xD;
      Some people (~1 in 500) suffer from a type of genetic heart condition known as hypertrophic&#xD;
      cardiomyopathy (HCM). This condition means that the muscle in the heart does not use energy&#xD;
      well and becomes larger than average, meaning that they have to tap into the heart's 'energy&#xD;
      reserves'. It is not known if nitrite has the same beneficial effects on heart muscle as on&#xD;
      other muscles in the body. Our study will explore the mechanism by which nitrite may improve&#xD;
      the function and energy status of the heart in HCM.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Anticipated">November 2017</start_date>
  <completion_date type="Anticipated">January 2019</completion_date>
  <primary_completion_date type="Anticipated">December 2018</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>Crossover Assignment</intervention_model>
    <intervention_model_description>This is a placebo-controlled, random-order mechanistic study of oral inorganic sodium nitrate versus placebo in cross-over fashion in patients with non obstructive hypertrophic cardiomyopathy and exercise limitation.</intervention_model_description>
    <primary_purpose>Other</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
    <masking_description>This will be a double blind study. The placebo and active treatments will appear identical and will be dispensed in identical containers. All trial patients, care providers, outcome assessors and data analysts will remain blind throughout the study.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Cardiac Energetic Status</measure>
    <time_frame>3 hours post dose of drug or placebo</time_frame>
    <description>Change in cardiac PCr/ATP ratio on phosphorus MRS between inorganic sodium nitrate and placebo</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Skeletal Muscle Mitochondrial Oxidative Capacity/Energetic Status</measure>
    <time_frame>3.5 hours post dose of drug or placebo</time_frame>
    <description>Change in PCr recovery half-time on dynamic phosphorus MRS between inorganic sodium nitrate and placebo</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cardiac Diastolic and Systolic Function on exercise</measure>
    <time_frame>3 hours post dose of drug or placebo</time_frame>
    <description>Change in measures of diastolic and systolic function on transthoracic echocardiogram at submaximal exercise between inorganic sodium nitrate and placebo</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cardiac Diastolic and Systolic Function at rest</measure>
    <time_frame>3 hours post dose of drug or placebo</time_frame>
    <description>Change in measures of diastolic and systolic function on transthoracic echocardiogram at rest between inorganic sodium nitrate and placebo</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Plasma levels of Nitrate/Nitrite/NOx</measure>
    <time_frame>3 hours post dose of drug or placebo</time_frame>
    <description>Change in blood plasma levels of Nitrate/Nitrite/NOx between inorganic sodium nitrate and placebo</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">18</enrollment>
  <condition>Cardiomyopathy, Hypertrophic</condition>
  <arm_group>
    <arm_group_label>Sodium Nitrate</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Following entry into the study, patients will receive a single dose of oral inorganic sodium nitrate (14mmol) on two separate visits, or matching placebo, in random order (i.e. 2x nitrate visits first or 2x placebo visits first) in a cross-over fashion.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Following entry into the study, patients will receive a single dose of oral inorganic sodium nitrate (14mmol) on two separate visits, or matching placebo, in random order (i.e. 2x nitrate visits first or 2x placebo visits first) in a cross-over fashion.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Sodium Nitrate</intervention_name>
    <description>Single dose of 14mmol oral inorganic sodium nitrate</description>
    <arm_group_label>Sodium Nitrate</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Single dose of oral matching placebo</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Phosphorous Magnetic Resonance Spectroscopy</intervention_name>
    <description>On the first visit day of this arm, participants will be lie inside an MRI scanner to take pictures of the heart. The thigh muscle will then be imaged before, during, and after kicking exercises.</description>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_label>Sodium Nitrate</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Exercise Stress Transthoracic Echocardiogram</intervention_name>
    <description>On the second visit day of this arm, participants will be asked to lie, semi-erect, on an exercise bed for up to 90 minutes. The echocardiogram will be performed at rest and during peak exercise. The exercise will be in the form of a pedal bike. The exercise levels will be worked out from an upright bicycle exercise test completed by the participants prior to randomization.</description>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_label>Sodium Nitrate</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male or female, aged between 18 and 80 years.&#xD;
&#xD;
          -  Able to provide informed consent.&#xD;
&#xD;
          -  Able to understand basic instructions in English.&#xD;
&#xD;
          -  A diagnosis of hypertrophic cardiomyopathy based on conventional transthoracic&#xD;
             echocardiogram guidelines: left ventricular wall thickness &gt;1.5cm in the absence of&#xD;
             sufficient alternative cause.&#xD;
&#xD;
          -  Exercise limited by symptoms on exertion (NYHA Class II symptoms or greater).&#xD;
&#xD;
          -  PeakVO2 &lt;80% on baseline CPEX.&#xD;
&#xD;
          -  The absence of resting LV outflow tract obstruction (peak gradient &lt;30 mm Hg) on TTE.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Significant medical, surgical or psychiatric disease that in the opinion of the&#xD;
             patient's attending physician would affect subject safety or influence the study&#xD;
             outcome.&#xD;
&#xD;
          -  Contraindications for undergoing MRI.&#xD;
&#xD;
          -  Hypotension with a systolic blood pressure &lt;90mmHg.&#xD;
&#xD;
          -  Severe anaemia with a plasma haemoglobin level &lt;8.0g/dL.&#xD;
&#xD;
          -  Known glucose-6-phosphate dehydrogenase (G6PD) deficiency or G6PD deficiency measured&#xD;
             at screening in males of African, Asian or Mediterranean decent.&#xD;
&#xD;
          -  Female subjects of childbearing potential.&#xD;
&#xD;
          -  Haemodynamically significant valve disease.&#xD;
&#xD;
          -  Predisposed to acute on chronic limb ischemia evident from a history of claudication&#xD;
             or known peripheral arterial disease.&#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>Michael P Frenneaux, MD</last_name>
    <role>Study Chair</role>
    <affiliation>University of East Anglia</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Sunil V Nair, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Norfolk and Norwich University Hospitals NHS Foundation Trust</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Brodie L Loudon, MBBS</last_name>
    <phone>44(0) 1603 591 216</phone>
    <email>b.loudon@uea.ac.uk</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Michael P Frenneaux, MD</last_name>
    <phone>44(0) 1603 593 061</phone>
    <email>m.frenneaux@uea.ac.uk</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Norfolk and Norwich University Hospitals NHS Foundation Trust</name>
      <address>
        <city>Norwich</city>
        <state>Norfolk</state>
        <zip>NR4 7UY</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Brodie L Loudon, MBBS</last_name>
      <phone>44(0) 1603 591 216</phone>
      <email>b.loudon@uea.ac.uk</email>
    </contact>
    <investigator>
      <last_name>Sunil V Nair, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Brodie L Loudon, MBBS</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>August 2017</verification_date>
  <study_first_submitted>August 11, 2017</study_first_submitted>
  <study_first_submitted_qc>August 11, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 16, 2017</study_first_posted>
  <last_update_submitted>October 24, 2017</last_update_submitted>
  <last_update_submitted_qc>October 24, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">October 25, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cardiomyopathies</mesh_term>
    <mesh_term>Cardiomyopathy, Hypertrophic</mesh_term>
    <mesh_term>Hypertrophy</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/NCT03251287
org study id: 201323
nct id: NCT03251287
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Inorganic nitrate, which is found at high levels in green leafy vegetables, is reduced to
      nitrite by bacteria in the mouth, swallowed, and absorbed in the stomach into the blood.
      Studies have shown that increasing the blood levels of nitrite improves the way that muscles
      use oxygen and energy during exercise, and potentially blood flow.

      Some people (~1 in 500) suffer from a type of genetic heart condition known as hypertrophic
      cardiomyopathy (HCM). This condition means that the muscle in the heart does not use energy
      well and becomes larger than average, meaning that they have to tap into the heart's 'energy
      reserves'. It is not known if nitrite has the same beneficial effects on heart muscle as on
      other muscles in the body. Our study will explore the mechanism by which nitrite may improve
      the function and energy status of the heart in HCM.
allocation: Randomized
intervention model: Crossover Assignment
intervention model description: This is a placebo-controlled, random-order mechanistic study of oral inorganic sodium nitrate versus placebo in cross-over fashion in patients with non obstructive hypertrophic cardiomyopathy and exercise limitation.
primary purpose: Other
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
masking description: This will be a double blind study. The placebo and active treatments will appear identical and will be dispensed in identical containers. All trial patients, care providers, outcome assessors and data analysts will remain blind throughout the study.
measure: Cardiac Energetic Status
time frame: 3 hours post dose of drug or placebo
description: Change in cardiac PCr/ATP ratio on phosphorus MRS between inorganic sodium nitrate and placebo
measure: Skeletal Muscle Mitochondrial Oxidative Capacity/Energetic Status
time frame: 3.5 hours post dose of drug or placebo
description: Change in PCr recovery half-time on dynamic phosphorus MRS between inorganic sodium nitrate and placebo
measure: Cardiac Diastolic and Systolic Function on exercise
time frame: 3 hours post dose of drug or placebo
description: Change in measures of diastolic and systolic function on transthoracic echocardiogram at submaximal exercise between inorganic sodium nitrate and placebo
measure: Cardiac Diastolic and Systolic Function at rest
time frame: 3 hours post dose of drug or placebo
description: Change in measures of diastolic and systolic function on transthoracic echocardiogram at rest between inorganic sodium nitrate and placebo
measure: Plasma levels of Nitrate/Nitrite/NOx
time frame: 3 hours post dose of drug or placebo
description: Change in blood plasma levels of Nitrate/Nitrite/NOx between inorganic sodium nitrate and placebo
arm group label: Sodium Nitrate
arm group type: Active Comparator
description: Following entry into the study, patients will receive a single dose of oral inorganic sodium nitrate (14mmol) on two separate visits, or matching placebo, in random order (i.e. 2x nitrate visits first or 2x placebo visits first) in a cross-over fashion.
arm group label: Placebo
arm group type: Placebo Comparator
description: Following entry into the study, patients will receive a single dose of oral inorganic sodium nitrate (14mmol) on two separate visits, or matching placebo, in random order (i.e. 2x nitrate visits first or 2x placebo visits first) in a cross-over fashion.
intervention type: Drug
intervention name: Sodium Nitrate
description: Single dose of 14mmol oral inorganic sodium nitrate
arm group label: Sodium Nitrate
intervention type: Drug
intervention name: Placebo
description: Single dose of oral matching placebo
arm group label: Placebo
intervention type: Diagnostic Test
intervention name: Phosphorous Magnetic Resonance Spectroscopy
description: On the first visit day of this arm, participants will be lie inside an MRI scanner to take pictures of the heart. The thigh muscle will then be imaged before, during, and after kicking exercises.
arm group label: Placebo
arm group label: Sodium Nitrate
intervention type: Diagnostic Test
intervention name: Exercise Stress Transthoracic Echocardiogram
description: On the second visit day of this arm, participants will be asked to lie, semi-erect, on an exercise bed for up to 90 minutes. The echocardiogram will be performed at rest and during peak exercise. The exercise will be in the form of a pedal bike. The exercise levels will be worked out from an upright bicycle exercise test completed by the participants prior to randomization.
arm group label: Placebo
arm group label: Sodium Nitrate
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
last name: Michael P Frenneaux, MD
role: Study Chair
affiliation: University of East Anglia
last name: Sunil V Nair, MD
role: Principal Investigator
affiliation: Norfolk and Norwich University Hospitals NHS Foundation Trust
last name: Brodie L Loudon, MBBS
phone: 44(0) 1603 591 216
email: b.loudon@uea.ac.uk
last name: Michael P Frenneaux, MD
phone: 44(0) 1603 593 061
email: m.frenneaux@uea.ac.uk
facility: 
status: Recruiting
contact: 
investigator: 
investigator: 
country: United Kingdom
responsible party type: Sponsor
mesh term: Cardiomyopathies
mesh term: Cardiomyopathy, Hypertrophic
mesh term: Hypertrophy
sharing ipd: No