xml: <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/NCT05976438</url>
    </required_header>
    <id_info>
      <org_study_id>A096461</org_study_id>
      <nct_id>NCT05976438</nct_id>
    </id_info>
    <brief_title>Skin Sodium and Salt Sensitivity of Blood Pressure</brief_title>
    <acronym>INTREPID</acronym>
    <official_title>Investigating the Relevance of Skin Sodium and Salt Sensitivity of Blood Pressure in Determining the Response to Anti-Hypertensive Drugs (INTREPID)</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Cambridge University Hospitals NHS Foundation Trust</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>King's College London</agency>
        <agency_class>Other</agency_class>
      </collaborator>
    </sponsors>
    <source>Cambridge University Hospitals NHS Foundation Trust</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>
        Eating too much salt raises blood pressure and the risk of having a heart attack or stroke.&#xD;
        The investigators do not fully understand why salt raises blood pressure, but storage of&#xD;
        sodium in the body, particularly in the skin, may be important. For this reason, the&#xD;
        investigators wish to study the link between skin sodium, blood pressure and cardiovascular&#xD;
        risk in patients with high blood pressure, of different ethnicities, using techniques such as&#xD;
        skin biopsy and magnetic resonance imaging (MRI). The results will provide detailed&#xD;
        information on skin sodium storage and help us better understand the effects of blood&#xD;
        pressure medications on these mechanisms. Ultimately, the investigators aim to develop&#xD;
        personalized treatment guidelines for clinical use.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        The physiological basis of salt sensitivity of blood pressure (SSBP) is poorly understood,&#xD;
        and determining which patients have SSBP is not straightforward. Furthermore, determining&#xD;
        salt sensitivity requires direct intervention tracking changes in blood pressure after salt&#xD;
        challenge or depletion over several days. This makes identifying salt-sensitive individuals&#xD;
        impractical in a clinical setting, hindering its application. It is crucial that the&#xD;
        investigators elucidate the underlying mechanisms of salt-sensitivity, and through this&#xD;
        understanding develop a biomarker of SSBP for clinical use.&#xD;
  &#xD;
        From a review of recent studies it appears that in the short-term, accumulation of skin&#xD;
        sodium during high salt intake attenuates the blood pressure response, while in the&#xD;
        long-term, high skin sodium levels indicate a tendency for SSBP, hypertension and elevated&#xD;
        cardiovascular risk. The reasons for this are not clear and merit further investigation. By&#xD;
        refining methods for quantification of skin sodium and expanding its use in hypertension&#xD;
        research, the clinicians can improve patient assessment, treatment prescription, and disease&#xD;
        monitoring.&#xD;
  &#xD;
        Using skin biopsy and sodium MRI provides a unique opportunity to study skin sodium handling&#xD;
        and SSBP during antihypertensive treatment, and can provide insights into why hypertensives&#xD;
        and certain ethnic groups have a higher incidence of SSBP. Sodium MRI may also help increase&#xD;
        our understanding of the mechanisms by which diuretics work, both systemically and in the&#xD;
        kidney and provide a way to identify salt-sensitive individuals for targeted clinical&#xD;
        intervention.&#xD;
  &#xD;
        Hypotheses:&#xD;
  &#xD;
          1. Skin sodium decreases with salt-dependent (diuretic) treatments but not salt-independent&#xD;
             (calcium channel blocker) treatments.&#xD;
  &#xD;
          2. Diuretic-induced reductions in skin sodium correlate with reductions in blood pressure.&#xD;
  &#xD;
          3. Skin sodium is higher in populations traditionally known to be more salt sensitive, such&#xD;
             hypertensive patients of black ethnicity.&#xD;
  &#xD;
        Patients will be enrolled on to a randomised, open-label, two-treatment two-period crossover&#xD;
        treatment. The hypertensive medication used in this study are Amlodipine 5 or 10mg and&#xD;
        Chlortalidone 25mg.&#xD;
  &#xD;
        The duration for individual participants will be approximately 16 weeks. Participants will&#xD;
        have a total of 7 visits including screening/enrolment (visit 1) and baseline visit (visit&#xD;
        2).&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">August 2023</start_date>
    <completion_date type="Anticipated">December 2024</completion_date>
    <primary_completion_date type="Anticipated">December 2024</primary_completion_date>
    <phase>N/A</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>Randomized</allocation>
      <intervention_model>Single Group Assignment</intervention_model>
      <primary_purpose>Basic Science</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Concentration of Skin sodium</measure>
      <time_frame>Approximately 8 weeks after receiving each treatment up to week 16 which will be the study completion week</time_frame>
      <description>This is planned for all participants</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Concentration of Skin Potassium</measure>
      <time_frame>Approximately 8 weeks after receiving each treatment up to week 16 which will be the study completion week</time_frame>
      <description>This is planned for all participants</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Systolic blood pressure</measure>
      <time_frame>All study visits - every 4 weeks up to week 16 which will be the study completion week</time_frame>
      <description>This is planned for all participants</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>MRI skin sodium concentration</measure>
      <time_frame>Approximately 8 weeks after receiving each treatment up to week 16 which will be the study completion week</time_frame>
      <description>This is planned for all participants</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Concentration of Skin glycosaminoglycans</measure>
      <time_frame>Approximately 8 weeks after receiving each treatment up to week 16 which will be the study completion week</time_frame>
      <description>This is planned for all participants</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Diastolic blood pressure</measure>
      <time_frame>All study visits - every 4 weeks up to week 16 which will be the study completion week</time_frame>
      <description>This is planned for all participants</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Body weight</measure>
      <time_frame>Body weight measurement will be performed at baseline only.</time_frame>
      <description>This is planned for all participants</description>
    </secondary_outcome>
    <other_outcome>
      <measure>Sodium MRI of kidney</measure>
      <time_frame>Approximately 8 weeks after receiving each treatment up to week 16 which will be the study completion week</time_frame>
      <description>This is planned for patients who consent to sodium imaging of kidney</description>
    </other_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">60</enrollment>
    <condition>Hypertension</condition>
    <arm_group>
      <arm_group_label>Open label arm 1</arm_group_label>
      <arm_group_type>Other</arm_group_type>
      <description>Participants will be randomised to AB sequence of drugs A: 1 to 2 weeks of Amlodipine 5mg followed by 6 to 7 weeks of Amlodipine 10mg B: Approximately 8 weeks of 25mg Chlortalidone</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Open label arm 2</arm_group_label>
      <arm_group_type>Other</arm_group_type>
      <description>Participants will be randomised to BA sequence of drugs B: Approximately 8 weeks of 25mg Chlortalidone A: 1 to 2 weeks of Amlodipine 5mg followed by 6 to 7 weeks of Amlodipine 10mg</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Amlodipine</intervention_name>
      <description>Amlodipine 5mg and Amlodipine 10mg will be one of the study drugs the patients will receive.</description>
      <arm_group_label>Open label arm 1</arm_group_label>
      <arm_group_label>Open label arm 2</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Chlortalidone</intervention_name>
      <description>Chlortalidone 25mg will be one of the study drugs the patients will receive.</description>
      <arm_group_label>Open label arm 1</arm_group_label>
      <arm_group_label>Open label arm 2</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. Have given written informed consent to participate&#xD;
  &#xD;
            2. Aged 18 or above&#xD;
  &#xD;
            3. Be hypertensive defined as:&#xD;
  &#xD;
                 1. Currently untreated with an ABPM day time average blood pressure or average home&#xD;
                    blood pressure of ≥135 mmHg (systolic) or ≥85 mmHg (diastolic)&#xD;
  &#xD;
                    OR&#xD;
  &#xD;
                 2. Patients who are taking antihypertensive drugs at sub therapeutic doses or in&#xD;
                    ineffective combinations, and who are felt likely to be controllable on a study&#xD;
                    drug and willing and able to be washed out, at the discretion of the CI/PI, can&#xD;
                    enter the study if they meet the above criteria.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. Uncontrolled blood pressure ≥ 180/110mmHg&#xD;
  &#xD;
            2. Known or suspected secondary hypertension&#xD;
  &#xD;
            3. Pregnant or breastfeeding women&#xD;
  &#xD;
            4. Significant sensitivity or contraindications to any of the study medications&#xD;
  &#xD;
            5. Participants taking lithium or are regularly consuming non-steroidal anti-inflammatory&#xD;
               drugs at variable doses&#xD;
  &#xD;
            6. Requirement to take any of the study drugs continuously e.g. ACEi and heart failure&#xD;
  &#xD;
            7. Any clinically significant hepatic impairment&#xD;
  &#xD;
            8. Any clinically significant kidney impairment&#xD;
  &#xD;
            9. Concurrent participation in another clinical trial or study using systemic vasoactive&#xD;
               medications or medications known to interact with the study drugs&#xD;
  &#xD;
           10. Patients who are deemed unsuitable by the investigator on clinical grounds e.g. an&#xD;
               abnormal heart rhythm due to Atrial Fibrillation (AF)&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>65 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Ian Wilkinson</last_name>
      <role>Principal Investigator</role>
      <affiliation>Cambridge University Hospitals NHS Foundation Trust</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Irene Sambath</last_name>
      <phone>01223 256621</phone>
      <email>irene.sambath@nhs.net</email>
    </overall_contact>
    <location>
      <facility>
        <name>Addenbrooke's Hospital</name>
        <address>
          <city>Cambridge</city>
          <country>United Kingdom</country>
        </address>
      </facility>
      <contact>
        <last_name>Irene Sambath</last_name>
        <email>cuh.intrepid@nhs.net</email>
      </contact>
    </location>
    <location>
      <facility>
        <name>St Thomas' Hospital</name>
        <address>
          <city>London</city>
          <country>United Kingdom</country>
        </address>
      </facility>
      <contact>
        <last_name>Luca Faconti</last_name>
      </contact>
    </location>
    <location_countries>
      <country>United Kingdom</country>
    </location_countries>
    <verification_date>July 2023</verification_date>
    <study_first_submitted>July 17, 2023</study_first_submitted>
    <study_first_submitted_qc>July 27, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 4, 2023</study_first_posted>
    <last_update_submitted>July 27, 2023</last_update_submitted>
    <last_update_submitted_qc>July 27, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 4, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Cambridge University Hospitals NHS Foundation Trust</investigator_affiliation>
      <investigator_full_name>Dr Ian B Wilkinson</investigator_full_name>
      <investigator_title>Prof</investigator_title>
    </responsible_party>
    <keyword>Skin Sodium</keyword>
    <keyword>Salt Sensitivity</keyword>
    <keyword>Blood Pressure</keyword>
    <keyword>Heart Disease</keyword>
    <keyword>Cardiovascular</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Hypersensitivity</mesh_term>
    </condition_browse>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Amlodipine</mesh_term>
      <mesh_term>Chlorthalidone</mesh_term>
    </intervention_browse>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT05976438
  org study id: A096461
  nct id: NCT05976438
  lead sponsor: 
  collaborator: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  Eating too much salt raises blood pressure and the risk of having a heart attack or stroke.
        The investigators do not fully understand why salt raises blood pressure, but storage of
        sodium in the body, particularly in the skin, may be important. For this reason, the
        investigators wish to study the link between skin sodium, blood pressure and cardiovascular
        risk in patients with high blood pressure, of different ethnicities, using techniques such as
        skin biopsy and magnetic resonance imaging (MRI). The results will provide detailed
        information on skin sodium storage and help us better understand the effects of blood
        pressure medications on these mechanisms. Ultimately, the investigators aim to develop
        personalized treatment guidelines for clinical use.
  The physiological basis of salt sensitivity of blood pressure (SSBP) is poorly understood,
        and determining which patients have SSBP is not straightforward. Furthermore, determining
        salt sensitivity requires direct intervention tracking changes in blood pressure after salt
        challenge or depletion over several days. This makes identifying salt-sensitive individuals
        impractical in a clinical setting, hindering its application. It is crucial that the
        investigators elucidate the underlying mechanisms of salt-sensitivity, and through this
        understanding develop a biomarker of SSBP for clinical use.
  
        From a review of recent studies it appears that in the short-term, accumulation of skin
        sodium during high salt intake attenuates the blood pressure response, while in the
        long-term, high skin sodium levels indicate a tendency for SSBP, hypertension and elevated
        cardiovascular risk. The reasons for this are not clear and merit further investigation. By
        refining methods for quantification of skin sodium and expanding its use in hypertension
        research, the clinicians can improve patient assessment, treatment prescription, and disease
        monitoring.
  
        Using skin biopsy and sodium MRI provides a unique opportunity to study skin sodium handling
        and SSBP during antihypertensive treatment, and can provide insights into why hypertensives
        and certain ethnic groups have a higher incidence of SSBP. Sodium MRI may also help increase
        our understanding of the mechanisms by which diuretics work, both systemically and in the
        kidney and provide a way to identify salt-sensitive individuals for targeted clinical
        intervention.
  
        Hypotheses:
  
          1. Skin sodium decreases with salt-dependent (diuretic) treatments but not salt-independent
             (calcium channel blocker) treatments.
  
          2. Diuretic-induced reductions in skin sodium correlate with reductions in blood pressure.
  
          3. Skin sodium is higher in populations traditionally known to be more salt sensitive, such
             hypertensive patients of black ethnicity.
  
        Patients will be enrolled on to a randomised, open-label, two-treatment two-period crossover
        treatment. The hypertensive medication used in this study are Amlodipine 5 or 10mg and
        Chlortalidone 25mg.
  
        The duration for individual participants will be approximately 16 weeks. Participants will
        have a total of 7 visits including screening/enrolment (visit 1) and baseline visit (visit
        2).
  allocation: Randomized
  intervention model: Single Group Assignment
  primary purpose: Basic Science
  masking: None (Open Label)
  measure: Concentration of Skin sodium
  time frame: Approximately 8 weeks after receiving each treatment up to week 16 which will be the study completion week
  description: This is planned for all participants
  measure: Concentration of Skin Potassium
  time frame: Approximately 8 weeks after receiving each treatment up to week 16 which will be the study completion week
  description: This is planned for all participants
  measure: Systolic blood pressure
  time frame: All study visits - every 4 weeks up to week 16 which will be the study completion week
  description: This is planned for all participants
  measure: MRI skin sodium concentration
  time frame: Approximately 8 weeks after receiving each treatment up to week 16 which will be the study completion week
  description: This is planned for all participants
  measure: Concentration of Skin glycosaminoglycans
  time frame: Approximately 8 weeks after receiving each treatment up to week 16 which will be the study completion week
  description: This is planned for all participants
  measure: Diastolic blood pressure
  time frame: All study visits - every 4 weeks up to week 16 which will be the study completion week
  description: This is planned for all participants
  measure: Body weight
  time frame: Body weight measurement will be performed at baseline only.
  description: This is planned for all participants
  measure: Sodium MRI of kidney
  time frame: Approximately 8 weeks after receiving each treatment up to week 16 which will be the study completion week
  description: This is planned for patients who consent to sodium imaging of kidney
  arm group label: Open label arm 1
  arm group type: Other
  description: Participants will be randomised to AB sequence of drugs A: 1 to 2 weeks of Amlodipine 5mg followed by 6 to 7 weeks of Amlodipine 10mg B: Approximately 8 weeks of 25mg Chlortalidone
  arm group label: Open label arm 2
  arm group type: Other
  description: Participants will be randomised to BA sequence of drugs B: Approximately 8 weeks of 25mg Chlortalidone A: 1 to 2 weeks of Amlodipine 5mg followed by 6 to 7 weeks of Amlodipine 10mg
  intervention type: Drug
  intervention name: Amlodipine
  description: Amlodipine 5mg and Amlodipine 10mg will be one of the study drugs the patients will receive.
  arm group label: Open label arm 1
  arm group label: Open label arm 2
  intervention type: Drug
  intervention name: Chlortalidone
  description: Chlortalidone 25mg will be one of the study drugs the patients will receive.
  arm group label: Open label arm 1
  arm group label: Open label arm 2
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 65 Years
  healthy volunteers: No
  last name: Ian Wilkinson
  role: Principal Investigator
  affiliation: Cambridge University Hospitals NHS Foundation Trust
  last name: Irene Sambath
  phone: 01223 256621
  email: irene.sambath@nhs.net
  facility: 
  contact: 
  facility: 
  contact: 
  country: United Kingdom
  responsible party type: Principal Investigator
  investigator affiliation: Cambridge University Hospitals NHS Foundation Trust
  investigator full name: Dr Ian B Wilkinson
  investigator title: Prof
  mesh term: Hypersensitivity
  mesh term: Amlodipine
  mesh term: Chlorthalidone