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/NCT05967715</url>
    </required_header>
    <id_info>
      <org_study_id>MicroFit</org_study_id>
      <nct_id>NCT05967715</nct_id>
    </id_info>
    <brief_title>Exercise Training Influences Gut Microbiota and Cardiovascular Health Through Inflammation Control in Adult Hypertensive Population: the MicroFit Study</brief_title>
    <official_title>Exercise Training Influences Gut Microbiota and Cardiovascular Health Through Inflammation Control in Adult Hypertensive Population: the MicroFit Study</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>University of Bologna</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>Actial Farmaceutica S.r.l.</agency>
        <agency_class>Industry</agency_class>
      </collaborator>
    </sponsors>
    <source>University of Bologna</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>
        Cardiovascular diseases are the number 1 cause of death globally, taking an estimated 17.9&#xD;
        million lives each year (31% of deaths worldwide). Hypertension, with 1.13 billion people&#xD;
        affected worldwide, is the leading risk factor for global mortality. Physical inactivity is&#xD;
        among the modifiable cardiovascular risk factors. While the beneficial effects of physical&#xD;
        activity on cardiovascular system are widely known, the mechanisms involved are not&#xD;
        completely understood. Both exercise training and hypertension are linked to inflammation.&#xD;
        Furthermore, there is evidence that gut microbiota regulates inflammatory patterns. Recent&#xD;
        investigations showed a relationship between exercise training and the&#xD;
        composition/functionality of the gut microbiota. Anyway, the modification of the composition&#xD;
        and functionality of the gut microbiota in hypertension due to the exercise training and the&#xD;
        relative involvement of oxidative stress and inflammation are not completely understood.&#xD;
  &#xD;
        In literature an association between gut microbiota composition and arterial stiffness is&#xD;
        described, in particular, the investigators observed both a direct correlation between&#xD;
        arterial stiffness and abundances of bacteria associated with altered gut permeability and&#xD;
        inflammation; and an inverse relationship between arterial stiffness, microbiota diversity,&#xD;
        and abundances of bacteria associated with most fit microbiota composition. Anyway, while&#xD;
        these association were stable in animal studies, in human studies none of the identified&#xD;
        interventional trials was able to demonstrate this relationship. Of note, only half of human&#xD;
        studies measured BP, and very few adjusted the vascular analyses for BP variation, which is a&#xD;
        major determinant of arterial stiffness.&#xD;
  &#xD;
        This is a non-profit, monocentric, non-pharmacological interventional study, a randomized&#xD;
        controlled trial with three intervention arms, partial double-blind, aiming to verify the&#xD;
        hypothesis that, in hypertensive patients in primary prevention with cardiovascular risk&#xD;
        factors, physical exercise favorably modifies the intestinal bacterial flora compared to the&#xD;
        probiotic, with a positive impact on cardiovascular health, and to demonstrate that this&#xD;
        involves inflammation modulation. There will be 3 intervention arms, with 1:1:1 stratified&#xD;
        randomization by gender: 1. Administration of controlled physical activity training; 2.&#xD;
        Administration of probiotic; 3. Administration of placebo. Arms 2 and 3 will be double-blind.&#xD;
        The intervention will last for three months, followed by a 6-month follow-up period.&#xD;
        Afterwards, the medical team may be contacted for further tests/assessments or simply for&#xD;
        information about the participant's health status, for a total duration of 24 months.&#xD;
  &#xD;
        The investigators hypothesize that hypertensive patients in cardiovascular primary prevention&#xD;
        have a dysbiotic gut microbial signatures, that could be a new marker of early vascular&#xD;
        aging. Secondly, the investigators anticipate that exercise training will modify both gut&#xD;
        microbiota and hemodynamic profile, and that a relationship exists between gut microbiota and&#xD;
        hemodynamic modifications. Thirdly, the investigators expect that the beneficial effects of&#xD;
        exercise training are driven by positive changes in the inflammatory modulators.&#xD;
      </textblock>
    </brief_summary>
    <overall_status>Recruiting</overall_status>
    <start_date type="Actual">April 3, 2023</start_date>
    <completion_date type="Anticipated">April 2, 2026</completion_date>
    <primary_completion_date type="Anticipated">April 2, 2026</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>Prevention</primary_purpose>
      <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
      <masking_description>Only for the &quot;probiotics&quot; and &quot;placebo&quot; arms</masking_description>
    </study_design_info>
    <primary_outcome>
      <measure>To describe the modification of the gut microbiota composition and function after the exercise training compared to probiotic supplements and to placebo.</measure>
      <time_frame>time 0 and 3 months</time_frame>
      <description>Changes in measures of gut microbiota composition and function from time 0 to 3 months (alpha diversity, beta diversity, taxonomy, relative abundance of microbial genes and pathways)</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>To describe the association between gut microbiota patterns with impaired central hemodynamics</measure>
      <time_frame>time 0 and 3 months</time_frame>
      <description>To measure the association of gut microbiota diversity indexes, taxonomy, relative abundance of microbial genes and pathways, with central hemodynamics parameters (central blood pressure, aortic stiffness, pulse pressure amplification, augmentation index).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>To test the association of the systemic inflammation with the modification of gut microbiota composition/functionality.</measure>
      <time_frame>time 0 and 3 months</time_frame>
      <description>To test the association between inflammatory markers (alpha-1-acid glycoprotein, high-sensitive c-reactive protein) and gut microbiota diversity indexes, taxonomy, relative abundance of microbial genes and pathways.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>To test the modification of endothelial function after the exercise training in comparison to probiotic supplements and placebo.</measure>
      <time_frame>time 0, and 3 months</time_frame>
      <description>To measure variation in endothelial glycocalyx thickness before and after 3-mo intervention</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>To identify the variation of the gut microbiota composition and function in the long term follow up after the intervention</measure>
      <time_frame>from 3 to 9 months.</time_frame>
      <description>Measures of gut microbiota diversity indexes, taxonomy, relative abundance of microbial genes and pathways at the end of the intervention (3 months) and after the 9-mo follow up.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>To describe the association between gut microbiota patterns with impaired central hemodynamics in the long term follow up 6 months after the intervention</measure>
      <time_frame>at 9-mo follow up</time_frame>
      <description>To measure the association of gut microbiota diversity indexes, taxonomy, relative abundance of microbial genes and pathways, with central hemodynamics parameters (central blood pressure, aortic stiffness, pulse pressure amplification, augmentation index)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>To test the association of the systemic inflammation with the modification of gut microbiota composition/functionality, after the long term follow up 6 months after the intervention.</measure>
      <time_frame>at 9-mo follow up</time_frame>
      <description>To test the association between inflammatory markers (alpha-1-acid glycoprotein, high-sensitive c-reactive protein) and gut microbiota diversity indexes, taxonomy, relative abundance of microbial genes and pathways, at 9-mo follow up.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>To test the modification of endothelial function after the exercise training in comparison to probiotic supplements and placebo, after the long term follow up 6 months after the intervention</measure>
      <time_frame>at 9-mo follow up</time_frame>
      <description>To measure variation in endothelial glycocalyx thickness at 9-mo follow up</description>
    </secondary_outcome>
    <number_of_arms>3</number_of_arms>
    <enrollment type="Anticipated">75</enrollment>
    <condition>Hypertension</condition>
    <condition>Microbiota</condition>
    <arm_group>
      <arm_group_label>Exercise training</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>high intensity interval training: thrice a week</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Probiotics</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>VSL#3# probiotic: twice daily</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Placebo</arm_group_label>
      <arm_group_type>Placebo Comparator</arm_group_type>
      <description>Comparator of the Probiotics arm</description>
    </arm_group>
    <intervention>
      <intervention_type>Behavioral</intervention_type>
      <intervention_name>exercise training</intervention_name>
      <description>high intensity interval training</description>
      <arm_group_label>Exercise training</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Other</intervention_type>
      <intervention_name>Probiotics</intervention_name>
      <description>VSL#3# Probiotic</description>
      <arm_group_label>Probiotics</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Other</intervention_type>
      <intervention_name>Placebo</intervention_name>
      <description>Probiotic Placebo</description>
      <arm_group_label>Placebo</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Arterial hypertension*;&#xD;
  &#xD;
            -  Stable antihypertensive therapy in the last 2 months, with controlled blood pressure&#xD;
               values;&#xD;
  &#xD;
            -  Age 40-65 years;&#xD;
  &#xD;
            -  Willing to sign the written informed consent;&#xD;
  &#xD;
            -  Written and spoken Italian language comprehension.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Atrial fibrillation;&#xD;
  &#xD;
            -  Diabetes mellitus either type I or II;&#xD;
  &#xD;
            -  Active cancer;&#xD;
  &#xD;
            -  Inflammatory bowel disease;&#xD;
  &#xD;
            -  Heart failure NYHA class III to IV;&#xD;
  &#xD;
            -  Recent antibiotic or probiotic treatment in the previous month for any reason;&#xD;
  &#xD;
            -  Recent myocardial infarction or hospital admission for any other reason in the&#xD;
               previous 6 months;&#xD;
  &#xD;
            -  Any other condition that the medical doctor (MD) considers to contraindicate the&#xD;
               participation in an exercise program of High intensity;&#xD;
  &#xD;
            -  Pulmonary disease requiring oxygen therapy;&#xD;
  &#xD;
            -  Relevant neurological condition impairing motor or cognitive function;&#xD;
  &#xD;
            -  Severe depressive disorder;&#xD;
  &#xD;
            -  Pregnancy.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>40 Years</minimum_age>
      <maximum_age>65 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_contact>
      <last_name>Davide Agnoletti, PhD</last_name>
      <phone>00390512145597</phone>
      <email>davide.agnoletti2@unibo.it</email>
    </overall_contact>
    <location>
      <facility>
        <name>University of Bologna</name>
        <address>
          <city>Bologna</city>
          <zip>40138</zip>
          <country>Italy</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Davide Agnoletti, PhD</last_name>
        <phone>00390512145579</phone>
        <email>davide.agnoletti2@unibo.it</email>
      </contact>
    </location>
    <location_countries>
      <country>Italy</country>
    </location_countries>
    <verification_date>July 2023</verification_date>
    <study_first_submitted>June 16, 2023</study_first_submitted>
    <study_first_submitted_qc>July 21, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 1, 2023</study_first_posted>
    <last_update_submitted>July 21, 2023</last_update_submitted>
    <last_update_submitted_qc>July 21, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 1, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>University of Bologna</investigator_affiliation>
      <investigator_full_name>Davide Agnoletti</investigator_full_name>
      <investigator_title>Assistant Professor</investigator_title>
    </responsible_party>
    <keyword>hypertension</keyword>
    <keyword>gut microbiota</keyword>
    <keyword>exercise training</keyword>
    <keyword>physical activity</keyword>
    <keyword>central hemodynamics</keyword>
    <keyword>arterial stiffness</keyword>
    <keyword>pulse wave velocity</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Hypertension</mesh_term>
      <mesh_term>Inflammation</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </patient_data>
    <!-- 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/NCT05967715
  org study id: MicroFit
  nct id: NCT05967715
  lead sponsor: 
  collaborator: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  Cardiovascular diseases are the number 1 cause of death globally, taking an estimated 17.9
        million lives each year (31% of deaths worldwide). Hypertension, with 1.13 billion people
        affected worldwide, is the leading risk factor for global mortality. Physical inactivity is
        among the modifiable cardiovascular risk factors. While the beneficial effects of physical
        activity on cardiovascular system are widely known, the mechanisms involved are not
        completely understood. Both exercise training and hypertension are linked to inflammation.
        Furthermore, there is evidence that gut microbiota regulates inflammatory patterns. Recent
        investigations showed a relationship between exercise training and the
        composition/functionality of the gut microbiota. Anyway, the modification of the composition
        and functionality of the gut microbiota in hypertension due to the exercise training and the
        relative involvement of oxidative stress and inflammation are not completely understood.
  
        In literature an association between gut microbiota composition and arterial stiffness is
        described, in particular, the investigators observed both a direct correlation between
        arterial stiffness and abundances of bacteria associated with altered gut permeability and
        inflammation; and an inverse relationship between arterial stiffness, microbiota diversity,
        and abundances of bacteria associated with most fit microbiota composition. Anyway, while
        these association were stable in animal studies, in human studies none of the identified
        interventional trials was able to demonstrate this relationship. Of note, only half of human
        studies measured BP, and very few adjusted the vascular analyses for BP variation, which is a
        major determinant of arterial stiffness.
  
        This is a non-profit, monocentric, non-pharmacological interventional study, a randomized
        controlled trial with three intervention arms, partial double-blind, aiming to verify the
        hypothesis that, in hypertensive patients in primary prevention with cardiovascular risk
        factors, physical exercise favorably modifies the intestinal bacterial flora compared to the
        probiotic, with a positive impact on cardiovascular health, and to demonstrate that this
        involves inflammation modulation. There will be 3 intervention arms, with 1:1:1 stratified
        randomization by gender: 1. Administration of controlled physical activity training; 2.
        Administration of probiotic; 3. Administration of placebo. Arms 2 and 3 will be double-blind.
        The intervention will last for three months, followed by a 6-month follow-up period.
        Afterwards, the medical team may be contacted for further tests/assessments or simply for
        information about the participant's health status, for a total duration of 24 months.
  
        The investigators hypothesize that hypertensive patients in cardiovascular primary prevention
        have a dysbiotic gut microbial signatures, that could be a new marker of early vascular
        aging. Secondly, the investigators anticipate that exercise training will modify both gut
        microbiota and hemodynamic profile, and that a relationship exists between gut microbiota and
        hemodynamic modifications. Thirdly, the investigators expect that the beneficial effects of
        exercise training are driven by positive changes in the inflammatory modulators.
  allocation: Randomized
  intervention model: Parallel Assignment
  primary purpose: Prevention
  masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
  masking description: Only for the "probiotics" and "placebo" arms
  measure: To describe the modification of the gut microbiota composition and function after the exercise training compared to probiotic supplements and to placebo.
  time frame: time 0 and 3 months
  description: Changes in measures of gut microbiota composition and function from time 0 to 3 months (alpha diversity, beta diversity, taxonomy, relative abundance of microbial genes and pathways)
  measure: To describe the association between gut microbiota patterns with impaired central hemodynamics
  time frame: time 0 and 3 months
  description: To measure the association of gut microbiota diversity indexes, taxonomy, relative abundance of microbial genes and pathways, with central hemodynamics parameters (central blood pressure, aortic stiffness, pulse pressure amplification, augmentation index).
  measure: To test the association of the systemic inflammation with the modification of gut microbiota composition/functionality.
  time frame: time 0 and 3 months
  description: To test the association between inflammatory markers (alpha-1-acid glycoprotein, high-sensitive c-reactive protein) and gut microbiota diversity indexes, taxonomy, relative abundance of microbial genes and pathways.
  measure: To test the modification of endothelial function after the exercise training in comparison to probiotic supplements and placebo.
  time frame: time 0, and 3 months
  description: To measure variation in endothelial glycocalyx thickness before and after 3-mo intervention
  measure: To identify the variation of the gut microbiota composition and function in the long term follow up after the intervention
  time frame: from 3 to 9 months.
  description: Measures of gut microbiota diversity indexes, taxonomy, relative abundance of microbial genes and pathways at the end of the intervention (3 months) and after the 9-mo follow up.
  measure: To describe the association between gut microbiota patterns with impaired central hemodynamics in the long term follow up 6 months after the intervention
  time frame: at 9-mo follow up
  description: To measure the association of gut microbiota diversity indexes, taxonomy, relative abundance of microbial genes and pathways, with central hemodynamics parameters (central blood pressure, aortic stiffness, pulse pressure amplification, augmentation index)
  measure: To test the association of the systemic inflammation with the modification of gut microbiota composition/functionality, after the long term follow up 6 months after the intervention.
  time frame: at 9-mo follow up
  description: To test the association between inflammatory markers (alpha-1-acid glycoprotein, high-sensitive c-reactive protein) and gut microbiota diversity indexes, taxonomy, relative abundance of microbial genes and pathways, at 9-mo follow up.
  measure: To test the modification of endothelial function after the exercise training in comparison to probiotic supplements and placebo, after the long term follow up 6 months after the intervention
  time frame: at 9-mo follow up
  description: To measure variation in endothelial glycocalyx thickness at 9-mo follow up
  arm group label: Exercise training
  arm group type: Experimental
  description: high intensity interval training: thrice a week
  arm group label: Probiotics
  arm group type: Active Comparator
  description: VSL#3# probiotic: twice daily
  arm group label: Placebo
  arm group type: Placebo Comparator
  description: Comparator of the Probiotics arm
  intervention type: Behavioral
  intervention name: exercise training
  description: high intensity interval training
  arm group label: Exercise training
  intervention type: Other
  intervention name: Probiotics
  description: VSL#3# Probiotic
  arm group label: Probiotics
  intervention type: Other
  intervention name: Placebo
  description: Probiotic Placebo
  arm group label: Placebo
  criteria: 
  gender: All
  minimum age: 40 Years
  maximum age: 65 Years
  healthy volunteers: No
  last name: Davide Agnoletti, PhD
  phone: 00390512145597
  email: davide.agnoletti2@unibo.it
  facility: 
  status: Recruiting
  contact: 
  country: Italy
  responsible party type: Principal Investigator
  investigator affiliation: University of Bologna
  investigator full name: Davide Agnoletti
  investigator title: Assistant Professor
  mesh term: Hypertension
  mesh term: Inflammation
  sharing ipd: No