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/NCT05970601</url>
    </required_header>
    <id_info>
      <org_study_id>2022-1844</org_study_id>
      <nct_id>NCT05970601</nct_id>
    </id_info>
    <brief_title>Effects of Sodium Chloride or Its Substitute Salt Potassium Chloride on Vascular Function</brief_title>
    <acronym>ESCAPE-SALT</acronym>
    <official_title>Effects of Sodium Chloride or Its Substitute Salt Potassium Chloride on Vascular Function and Immune Response - a Randomized Controlled Trial</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Prof. Dr. med. Johannes Stegbauer</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Heinrich-Heine University, Duesseldorf</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>
        This is a prospective, monocentric, randomized trial to investigate how sodium chloride or&#xD;
        its substitute potassium chloride acutely affects vascular function by ingestion via a salted&#xD;
        soup. Furthermore we want to get insights on the pathophysiology by analyzing metabolism and&#xD;
        cell function in relation to vascular reaction.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Some of the leading death causes in western countries are attributed to artheriosclerosis&#xD;
        with its consequences especially cardiovascular events. Beside lifestyle risk factors such as&#xD;
        physical inactivity, adipositas and stress, high dietary sodium intake is one of the easiest&#xD;
        modifiable factors to reduce development and progession of artheriosclerosis. Unfortunately&#xD;
        high sodium diet is one of the hallmarks of western diet. Epidemiologic and experimental data&#xD;
        have provided compelling evidence that high salt and its induced elevation in bloodpressure&#xD;
        is an important factor in the development and progression of cardiovascular disease,&#xD;
        artheriosclerosis with its endorgan failure.&#xD;
  &#xD;
        To analyze the reasons for the hazardous effects of high oral sodium chloride exposure on&#xD;
        vascular damage and a possible protective mechanism by the salt substitute potassium&#xD;
        chloride, we intend to conduct a single-center randomized trial (ESCAPE-SALT). We aim to&#xD;
        measure vascular function by flow mediated dilation (FMD) and dynamic vessel analysis (DVA)&#xD;
        of retinal mircocirculation. Participants will be divided into 3 groups. Each group will be&#xD;
        served a soup with different salt content. The salt composition is as follows: soup A (9 g&#xD;
        sodium chloride), soup B (6 g sodium chloride plus 3 g potassium chloride), and soup C (6 g&#xD;
        sodium chloride). The effects on blood pressure, body composition markers, electrolytes,&#xD;
        inflammatory and metabolic response, and vascular function are measured before, 4 and 24 h&#xD;
        after ingestion of the soup. Furthermore we will investigate the underlying mechanism by&#xD;
        performing metabolomic, transcriptomic and proteomic anyalysis.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">August 1, 2023</start_date>
    <completion_date type="Anticipated">October 2026</completion_date>
    <primary_completion_date type="Anticipated">June 2025</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>Parallel Assignment</intervention_model>
      <primary_purpose>Basic Science</primary_purpose>
      <masking>Double (Participant, Investigator)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Effect of a single oral high-sodium chloride load or a partial substitution by potassium chloride on retinal vessel diameter and the flicker-light-induced retinal vessel dilatation.</measure>
      <time_frame>Baseline, 4 hours, 24 hours</time_frame>
      <description>Flicker-induced dilatation and diameter of fundus vessels will be measured via funduscopy in a static an dynamic analysis before, 4 hours and 24 hours after ingestion of a salty soup and the change between the timepoints will be analyzed. First the diameter of venoles and arterioles in µm and their ratio are measured in a standardized fundus picture. In a second step we will film the fundus during three flicker-light periods of 20 seconds and measure the dilatation in percent during the flicker period.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Effect of a single oral high-sodium chloride load or a partial substitution by potassium chloride on hypoxia-induced dilatation of brachial artery.</measure>
      <time_frame>Baseline, 4 hours, 24 hours</time_frame>
      <description>Flow mediated dilatation (FMD) as a marker for macrovascular function will be measured at baseline, 4 hours and 24 hours after ingestion of a salty soup. We will measure FMD by ultrasound based measurement of brachial artery diameter in mm before and after induced hypoxia for 5 minutes. The change of dilatation in percentage between the different timepoints will be analyzed.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Effect of a single oral high-sodium chloride load or a partial substitution by potassium chloride on mitochondrial respiration capacity in PBMC.</measure>
      <time_frame>Baseline, 4 hours, 24 hours</time_frame>
      <description>Analysis of mitochondrial respiration capacity via seahorse technology in isolated PBMC from baseline, 4 and 24 hours after salt intake. The oxygen consumption rate (OCR) will be measured and the changes between the timepoints will be analyzed.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Effect of a single oral high-sodium chloride load or a partial substitution by potassium chloride on NO metabolism in serum and red blood cells.</measure>
      <time_frame>Baseline, 4 hours, 24 hours</time_frame>
      <description>We will measure the amount of nitrite and nitrate in red blood cells and serum by gas chemiluminescence at baseline, 4 and 24 hours after salt intake. The change between the three timepoints will be measured.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Effect of a single oral high-sodium chloride load or a partial substitution by potassium on metabolic profile in PBMC and plasma.</measure>
      <time_frame>Baseline, 4 hours, 24 hours</time_frame>
      <description>We will investigate the effect of a single oral high-sodium chloride load or a partial substitution by potassium on the metabolic profile in PBMCs and theplasma. The metabolites will be measured by liquid chromotagraphy and high resolution tandem mass spectrometry at baseline, 4 hours and 24 hours after salt intake. The difference between the timepoints will be analyzed.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Effect of a single oral high-sodium chloride load or a partial substitution by potassium on systemic inflammation markers.</measure>
      <time_frame>Baseline, 4 hours, 24 hours</time_frame>
      <description>Inflammatory markers such as cytokines will be meassured at baseline, 4 and 24 hours after salt intake by ELISA and OLINK. Changes of these markers between the three timepoints will be analyzed.</description>
    </secondary_outcome>
    <other_outcome>
      <measure>Effect of a single oral high-sodium chloride load or a partial substitution by potassium chloride on fluid body composition.</measure>
      <time_frame>Baseline, 4 hours, 24 hours</time_frame>
      <description>Analysis of fluid body composition and intra- and extracellular water amount by bioimpendance monitoring at baseline, 4 and 24 hours after salt intake. The changes in body composition between the three timepoints will be measured.</description>
    </other_outcome>
    <other_outcome>
      <measure>Effect of a single oral high-sodium chloride load or a partial substitution by potassium chloride on blood pressure.</measure>
      <time_frame>Baseline, 4 hours, 24 hours</time_frame>
      <description>Analysis of blood pressure by automated office blood pressure device at baseline, 4 hours and 24 hours after salt intake. The changes in blood pressure between the three timepoints will be measured.</description>
    </other_outcome>
    <other_outcome>
      <measure>Effect of a single oral high-sodium chloride load or a partial substitution by potassium chloride on renin-angiotensine-aldosterone system.</measure>
      <time_frame>Baseline, 4 hours, 24 hours</time_frame>
      <description>Analysis of renin, angiotensine and aldosterone levels at baseline, 4 hours and 24 hours after salt intake, measurement will be done in the clinical routine laboratory and the difference between timepoints will be analyzed.</description>
    </other_outcome>
    <other_outcome>
      <measure>Effect of a single oral high-sodium chloride load or a partial substitution by potassium on fecal microbiome.</measure>
      <time_frame>up to 48 hours before and after salt intake</time_frame>
      <description>Analysis of the change of fecal microbiome composition in microbiology of probes before and after salt intake.</description>
    </other_outcome>
    <other_outcome>
      <measure>Effect of a single oral high-sodium chloride load or a partial substitution by potassium on metabolomics in stool.</measure>
      <time_frame>up to 48 hours before and after salt intake</time_frame>
      <description>Analysis of the change of metabolomics in stool and serum after salt intake using liquid chromotagraphy and high resolution tandem mass spectrometry.</description>
    </other_outcome>
    <number_of_arms>3</number_of_arms>
    <enrollment type="Anticipated">60</enrollment>
    <condition>Vascular Function</condition>
    <condition>Healthy</condition>
    <condition>Diabetes</condition>
    <arm_group>
      <arm_group_label>high salt group</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Intake of 9 g sodium chloride</description>
    </arm_group>
    <arm_group>
      <arm_group_label>low salt group</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>Intake of 6 g sodium chloride</description>
    </arm_group>
    <arm_group>
      <arm_group_label>substitution group</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>Intake of 6 g sodium chloride plus 3 g potassium chloride</description>
    </arm_group>
    <intervention>
      <intervention_type>Dietary Supplement</intervention_type>
      <intervention_name>Soup</intervention_name>
      <description>Intake of a single soup with different sodium chloride and potassium chloride content</description>
      <arm_group_label>high salt group</arm_group_label>
      <arm_group_label>low salt group</arm_group_label>
      <arm_group_label>substitution group</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  full-aged&#xD;
  &#xD;
            -  signed informed consent&#xD;
  &#xD;
            -  no dietary restrictions&#xD;
  &#xD;
            -  access to retina for microvascular measurement&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  age &lt;18 y&#xD;
  &#xD;
            -  no retinal access for microvascular measurement&#xD;
  &#xD;
            -  known glaucoma&#xD;
  &#xD;
            -  antibiotic therapy within the last 4 weeks&#xD;
  &#xD;
            -  immunosuppressive Therapie within the last 4 weeks (e.g. glucocorticoids)&#xD;
  &#xD;
            -  s.p. malignancy&#xD;
  &#xD;
            -  unknown fever within the last 4 weeks&#xD;
  &#xD;
            -  salt wasting syndroms (e.g. renal tubular acidosis, Diabetes insipidus)&#xD;
  &#xD;
            -  chronic kidney disease stage 4-5&#xD;
  &#xD;
            -  known electrolyte disorder (e.g. hyperkalaemia, hypokalaemia, hypernatriaemia,&#xD;
               hyponatriaema)&#xD;
  &#xD;
            -  no or rejected informed consent&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>N/A</maximum_age>
      <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
    </eligibility>
    <overall_contact>
      <last_name>Johannes Stegbauer, Prof.Dr.med.</last_name>
      <phone>+492118117502</phone>
      <email>johannes.stegbauer@med.uni-duesseldorf.de</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Claudia Schmidt, PhD</last_name>
      <phone>+492118108074</phone>
      <email>claudia.schmidt@med.uni-duesseldorf.de</email>
    </overall_contact_backup>
    <verification_date>July 2023</verification_date>
    <study_first_submitted>July 8, 2023</study_first_submitted>
    <study_first_submitted_qc>July 28, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 1, 2023</study_first_posted>
    <last_update_submitted>July 28, 2023</last_update_submitted>
    <last_update_submitted_qc>July 28, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 1, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor-Investigator</responsible_party_type>
      <investigator_affiliation>Heinrich-Heine University, Duesseldorf</investigator_affiliation>
      <investigator_full_name>Prof. Dr. med. Johannes Stegbauer</investigator_full_name>
      <investigator_title>Assistant Professor</investigator_title>
    </responsible_party>
    <keyword>potassium chloride</keyword>
    <keyword>sodium chloride</keyword>
    <keyword>microcirculation</keyword>
    <!-- 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/NCT05970601
  org study id: 2022-1844
  nct id: NCT05970601
  lead sponsor: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  This is a prospective, monocentric, randomized trial to investigate how sodium chloride or
        its substitute potassium chloride acutely affects vascular function by ingestion via a salted
        soup. Furthermore we want to get insights on the pathophysiology by analyzing metabolism and
        cell function in relation to vascular reaction.
  Some of the leading death causes in western countries are attributed to artheriosclerosis
        with its consequences especially cardiovascular events. Beside lifestyle risk factors such as
        physical inactivity, adipositas and stress, high dietary sodium intake is one of the easiest
        modifiable factors to reduce development and progession of artheriosclerosis. Unfortunately
        high sodium diet is one of the hallmarks of western diet. Epidemiologic and experimental data
        have provided compelling evidence that high salt and its induced elevation in bloodpressure
        is an important factor in the development and progression of cardiovascular disease,
        artheriosclerosis with its endorgan failure.
  
        To analyze the reasons for the hazardous effects of high oral sodium chloride exposure on
        vascular damage and a possible protective mechanism by the salt substitute potassium
        chloride, we intend to conduct a single-center randomized trial (ESCAPE-SALT). We aim to
        measure vascular function by flow mediated dilation (FMD) and dynamic vessel analysis (DVA)
        of retinal mircocirculation. Participants will be divided into 3 groups. Each group will be
        served a soup with different salt content. The salt composition is as follows: soup A (9 g
        sodium chloride), soup B (6 g sodium chloride plus 3 g potassium chloride), and soup C (6 g
        sodium chloride). The effects on blood pressure, body composition markers, electrolytes,
        inflammatory and metabolic response, and vascular function are measured before, 4 and 24 h
        after ingestion of the soup. Furthermore we will investigate the underlying mechanism by
        performing metabolomic, transcriptomic and proteomic anyalysis.
  allocation: Randomized
  intervention model: Parallel Assignment
  primary purpose: Basic Science
  masking: Double (Participant, Investigator)
  measure: Effect of a single oral high-sodium chloride load or a partial substitution by potassium chloride on retinal vessel diameter and the flicker-light-induced retinal vessel dilatation.
  time frame: Baseline, 4 hours, 24 hours
  description: Flicker-induced dilatation and diameter of fundus vessels will be measured via funduscopy in a static an dynamic analysis before, 4 hours and 24 hours after ingestion of a salty soup and the change between the timepoints will be analyzed. First the diameter of venoles and arterioles in µm and their ratio are measured in a standardized fundus picture. In a second step we will film the fundus during three flicker-light periods of 20 seconds and measure the dilatation in percent during the flicker period.
  measure: Effect of a single oral high-sodium chloride load or a partial substitution by potassium chloride on hypoxia-induced dilatation of brachial artery.
  time frame: Baseline, 4 hours, 24 hours
  description: Flow mediated dilatation (FMD) as a marker for macrovascular function will be measured at baseline, 4 hours and 24 hours after ingestion of a salty soup. We will measure FMD by ultrasound based measurement of brachial artery diameter in mm before and after induced hypoxia for 5 minutes. The change of dilatation in percentage between the different timepoints will be analyzed.
  measure: Effect of a single oral high-sodium chloride load or a partial substitution by potassium chloride on mitochondrial respiration capacity in PBMC.
  time frame: Baseline, 4 hours, 24 hours
  description: Analysis of mitochondrial respiration capacity via seahorse technology in isolated PBMC from baseline, 4 and 24 hours after salt intake. The oxygen consumption rate (OCR) will be measured and the changes between the timepoints will be analyzed.
  measure: Effect of a single oral high-sodium chloride load or a partial substitution by potassium chloride on NO metabolism in serum and red blood cells.
  time frame: Baseline, 4 hours, 24 hours
  description: We will measure the amount of nitrite and nitrate in red blood cells and serum by gas chemiluminescence at baseline, 4 and 24 hours after salt intake. The change between the three timepoints will be measured.
  measure: Effect of a single oral high-sodium chloride load or a partial substitution by potassium on metabolic profile in PBMC and plasma.
  time frame: Baseline, 4 hours, 24 hours
  description: We will investigate the effect of a single oral high-sodium chloride load or a partial substitution by potassium on the metabolic profile in PBMCs and theplasma. The metabolites will be measured by liquid chromotagraphy and high resolution tandem mass spectrometry at baseline, 4 hours and 24 hours after salt intake. The difference between the timepoints will be analyzed.
  measure: Effect of a single oral high-sodium chloride load or a partial substitution by potassium on systemic inflammation markers.
  time frame: Baseline, 4 hours, 24 hours
  description: Inflammatory markers such as cytokines will be meassured at baseline, 4 and 24 hours after salt intake by ELISA and OLINK. Changes of these markers between the three timepoints will be analyzed.
  measure: Effect of a single oral high-sodium chloride load or a partial substitution by potassium chloride on fluid body composition.
  time frame: Baseline, 4 hours, 24 hours
  description: Analysis of fluid body composition and intra- and extracellular water amount by bioimpendance monitoring at baseline, 4 and 24 hours after salt intake. The changes in body composition between the three timepoints will be measured.
  measure: Effect of a single oral high-sodium chloride load or a partial substitution by potassium chloride on blood pressure.
  time frame: Baseline, 4 hours, 24 hours
  description: Analysis of blood pressure by automated office blood pressure device at baseline, 4 hours and 24 hours after salt intake. The changes in blood pressure between the three timepoints will be measured.
  measure: Effect of a single oral high-sodium chloride load or a partial substitution by potassium chloride on renin-angiotensine-aldosterone system.
  time frame: Baseline, 4 hours, 24 hours
  description: Analysis of renin, angiotensine and aldosterone levels at baseline, 4 hours and 24 hours after salt intake, measurement will be done in the clinical routine laboratory and the difference between timepoints will be analyzed.
  measure: Effect of a single oral high-sodium chloride load or a partial substitution by potassium on fecal microbiome.
  time frame: up to 48 hours before and after salt intake
  description: Analysis of the change of fecal microbiome composition in microbiology of probes before and after salt intake.
  measure: Effect of a single oral high-sodium chloride load or a partial substitution by potassium on metabolomics in stool.
  time frame: up to 48 hours before and after salt intake
  description: Analysis of the change of metabolomics in stool and serum after salt intake using liquid chromotagraphy and high resolution tandem mass spectrometry.
  arm group label: high salt group
  arm group type: Experimental
  description: Intake of 9 g sodium chloride
  arm group label: low salt group
  arm group type: Active Comparator
  description: Intake of 6 g sodium chloride
  arm group label: substitution group
  arm group type: Active Comparator
  description: Intake of 6 g sodium chloride plus 3 g potassium chloride
  intervention type: Dietary Supplement
  intervention name: Soup
  description: Intake of a single soup with different sodium chloride and potassium chloride content
  arm group label: high salt group
  arm group label: low salt group
  arm group label: substitution group
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: Accepts Healthy Volunteers
  last name: Johannes Stegbauer, Prof.Dr.med.
  phone: +492118117502
  email: johannes.stegbauer@med.uni-duesseldorf.de
  last name: Claudia Schmidt, PhD
  phone: +492118108074
  email: claudia.schmidt@med.uni-duesseldorf.de
  responsible party type: Sponsor-Investigator
  investigator affiliation: Heinrich-Heine University, Duesseldorf
  investigator full name: Prof. Dr. med. Johannes Stegbauer
  investigator title: Assistant Professor