<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/NCT04466072</url>
  </required_header>
  <id_info>
    <org_study_id>IRB202001134</org_study_id>
    <nct_id>NCT04466072</nct_id>
  </id_info>
  <brief_title>Gut Microbiome and Ventricular Arrhythmias</brief_title>
  <official_title>The Correlation Between Gut Microbiome-host Interaction and Ventricular Arrhythmias</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>North Florida Foundation for Research and Education</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>North Florida Foundation for Research and Education</source>
  <oversight_info>
    <has_dmc>Yes</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>
      Ventricular tachycardia and ventricular fibrillation (VT/VF) are the most common causes of&#xD;
      sudden cardiac death in patients with diseased hearts. The factors contributing to these&#xD;
      deadly arrhythmias are not well understood.&#xD;
&#xD;
      The presence of a wide variety of microbial flora in the human GI tract, particularly colon&#xD;
      has been well recognized for a long time. There are also emerging links showing the effect of&#xD;
      an intact gut microbiome having effects on left ventricular remodeling after myocardial&#xD;
      infarction and hypertension. Gut microbiota has also been associated with outcomes in atrial&#xD;
      fibrillation.&#xD;
&#xD;
      There is little available in current literature showing a relationship between gut microbiome&#xD;
      characteristics and ventricular arrhythmia burden. The gut microbiome has particularly strong&#xD;
      interactions with neuroendocrine and immunologic mediators and has effects on the modulation&#xD;
      of the autonomic nervous system. These systems are also hypothesized to influence ventricular&#xD;
      arrhythmias. The investigators propose to study the relation and interaction between gut&#xD;
      microbiome and ventricular arrhythmogenesis.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Specific Aims:&#xD;
&#xD;
      Aim 1: To identify specific gut microbiome characteristics of patients who are prone to&#xD;
      clinically significant or high burden of ventricular arrhythmias compared with patients with&#xD;
      similar conventional risk factors and low burden of ventricular arrhythmias.&#xD;
&#xD;
      Aim 2: To examine changes that occur in the gut microbiome composition after treatment of&#xD;
      ventricular arrhythmias.&#xD;
&#xD;
      Research Plan:&#xD;
&#xD;
      This study will enroll 30 subjects recruited from the electrophysiology device clinic at the&#xD;
      VA medical center, who are individuals with underlying cardiomyopathy and prone to&#xD;
      ventricular arrhythmias.&#xD;
&#xD;
      Out of this cohort, the investigators will identify 2 groups who have different ventricular&#xD;
      arrhythmia burden despite similar conventional clinical factors.&#xD;
&#xD;
      This information regarding ventricular arrhythmia burden will be obtained from device&#xD;
      interrogation at the time of recruitment. Our proposal is study and compare the fecal&#xD;
      microbial composition of these groups to analyze association with ventricular arrhythmia&#xD;
      burden. Patients will provide a fecal sample for analysis at the time of enrollment.&#xD;
&#xD;
      After clinically indicated treatment in the high ventricular arrhythmia group, the&#xD;
      investigators will retest fecal samples to assess for changes in characteristics after&#xD;
      treatment. This will be done to study changes in the gut microbiome with ventricular&#xD;
      arrhythmia in the same individual.&#xD;
&#xD;
      After initial testing of the high burden group, they will undergo treatment aimed at&#xD;
      decreasing their burden of arrhythmia, with some combination of anti-arrhythmic drugs,&#xD;
      sympathetic blockade, or ventricular tachycardia ablation. After demonstrating a period of 3&#xD;
      months without sustained VT/VF on device interrogation, their fecal samples will be&#xD;
      re-analyzed. If a patient continues to have VT/VF requiring intermittent device therapies&#xD;
      despite a 6 month period of intensification of therapy, their fecal sample will be&#xD;
      re-analyzed after that 6 month timeframe.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">November 30, 2020</start_date>
  <completion_date type="Anticipated">December 31, 2024</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2024</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Control</observational_model>
    <time_perspective>Retrospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Difference in microbial composition of gut microbiome in study and control groups</measure>
    <time_frame>1 year</time_frame>
    <description>Microbial components identified through genetics will be compared between groups.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in microbial composition of gut microbiome after successful VT therapy</measure>
    <time_frame>1 year</time_frame>
    <description>Microbial components identified through genetics will be compared before and after VT therapy in the high VT burden group.</description>
  </secondary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Anticipated">30</enrollment>
  <condition>Ventricular Tachycardia</condition>
  <condition>Ventricular Fibrillation</condition>
  <condition>Gut Microbiome</condition>
  <arm_group>
    <arm_group_label>High Ventricular Arrhythmia burden group</arm_group_label>
    <description>Inclusion criteria for all groups:&#xD;
age &gt;18 years-old&#xD;
competent and willing to provide consent&#xD;
presence of implantable cardioverter-defibrillator&#xD;
diagnosis of cardiomyopathy&#xD;
left ventricular ejection fraction of 35% or less as assessed by echocardiogram within 1 year prior to enrollment&#xD;
Inclusion criteria for high ventricular arrhythmia burden group:&#xD;
• at least one episode of sustained VT/VF or VT/VF requiring ICD therapies within the preceding 3 months as assessed on device interrogation at the time of study enrollment&#xD;
Both groups will have stool sample collected for microbial analysis. This is anticipated twice for the high ventricular arrhythmia (VA) burden group. Once at the time of diagnosis of VA and later after the clinically indicated treatment for the VA.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control group</arm_group_label>
    <description>Inclusion criteria for all groups:&#xD;
age &gt;18 years-old&#xD;
competent and willing to provide consent&#xD;
presence of implantable cardioverter-defibrillator&#xD;
diagnosis of cardiomyopathy&#xD;
left ventricular ejection fraction of 35% or less as assessed by echocardiogram within 1 year prior to enrollment&#xD;
Inclusion criteria for control group:&#xD;
• no VT/VF on device interrogation for a period of at least 3 months preceding study enrollment&#xD;
Both groups will have stool sample collected for microbial analysis. This is anticipated only once for the control group.</description>
  </arm_group>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Stool test for microbial analysis</intervention_name>
    <description>Fecal samples will be analyzed by shotgun metagenomics and sample from the high ventricular arrhythmia burden will be compared with those from comparable control patients with low ventricular arrhythmia burden.</description>
    <arm_group_label>Control group</arm_group_label>
    <arm_group_label>High Ventricular Arrhythmia burden group</arm_group_label>
  </intervention>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Stool samples will be collected and analyzed for bacterial DNA analysis to characterize&#xD;
      nature and function of microbial flora. Host human DNA may be a contaminant&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Patients with underlying cardiomyopathy and having an implantable cardioverter&#xD;
        defibrillator for protection from ventricular arrhythmias.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Inclusion criteria for all groups:&#xD;
&#xD;
               -  age &gt;18 years-old&#xD;
&#xD;
               -  competent and willing to provide consent&#xD;
&#xD;
               -  presence of implantable cardioverter-defibrillator&#xD;
&#xD;
               -  diagnosis of cardiomyopathy&#xD;
&#xD;
               -  left ventricular ejection fraction of 35% or less as assessed by echocardiogram&#xD;
                  within 1 year prior to enrollment&#xD;
&#xD;
          -  Inclusion criteria for control group:&#xD;
&#xD;
             • no VT/VF on device interrogation for a period of at least 3 months preceding study&#xD;
             enrollment&#xD;
&#xD;
          -  Inclusion criteria for high ventricular arrhythmia burden group:&#xD;
&#xD;
               -  at least one episode of sustained VT/VF or VT/VF requiring ICD therapies within&#xD;
                  the preceding 3 months as assessed on device interrogation at the time of study&#xD;
                  enrollment&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  currently pregnant or have been pregnant in the last 6 months&#xD;
&#xD;
          -  antibiotic treatment within 5 months of study enrollment (i.e. antibiotic therapy in&#xD;
             the two months prior to the 3-month period of analysis for VT/VF)&#xD;
&#xD;
          -  chronic use of medications/supplements that can potentially affect gut microbiota&#xD;
             (i.e. probiotics, anti-inflammatory agents, glucocorticoids, other immune modulating&#xD;
             medications, antacids or proton pump inhibitors)&#xD;
&#xD;
          -  history of intestinal surgery, inflammatory bowel disease, celiac disease, lactose&#xD;
             intolerance, chronic pancreatitis, or other malabsorption disorder&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Ramil Goel, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Malcolm Randall VAMC</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Ramil Goel, MD</last_name>
    <phone>7165533752</phone>
    <email>ramilgoel@hotmail.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>Malcolm Randall VA medical center</name>
      <address>
        <city>Gainesville</city>
        <state>Florida</state>
        <zip>32608</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Ramil Goel</last_name>
      <phone>716-553-3752</phone>
      <email>ramilgoel@hotmail.com</email>
    </contact>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>April 2022</verification_date>
  <study_first_submitted>July 7, 2020</study_first_submitted>
  <study_first_submitted_qc>July 7, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 10, 2020</study_first_posted>
  <last_update_submitted>April 11, 2022</last_update_submitted>
  <last_update_submitted_qc>April 11, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">April 18, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>North Florida Foundation for Research and Education</investigator_affiliation>
    <investigator_full_name>Ramil Goel</investigator_full_name>
    <investigator_title>Clinical Electrophysiologist, Malcolm Randall VAMC, Gainesville</investigator_title>
  </responsible_party>
  <keyword>Ventricular arrhythmias</keyword>
  <keyword>microbiome</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Arrhythmias, Cardiac</mesh_term>
    <mesh_term>Tachycardia</mesh_term>
    <mesh_term>Tachycardia, Ventricular</mesh_term>
    <mesh_term>Ventricular Fibrillation</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/NCT04466072
org study id: IRB202001134
nct id: NCT04466072
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Ventricular tachycardia and ventricular fibrillation (VT/VF) are the most common causes of
      sudden cardiac death in patients with diseased hearts. The factors contributing to these
      deadly arrhythmias are not well understood.

      The presence of a wide variety of microbial flora in the human GI tract, particularly colon
      has been well recognized for a long time. There are also emerging links showing the effect of
      an intact gut microbiome having effects on left ventricular remodeling after myocardial
      infarction and hypertension. Gut microbiota has also been associated with outcomes in atrial
      fibrillation.

      There is little available in current literature showing a relationship between gut microbiome
      characteristics and ventricular arrhythmia burden. The gut microbiome has particularly strong
      interactions with neuroendocrine and immunologic mediators and has effects on the modulation
      of the autonomic nervous system. These systems are also hypothesized to influence ventricular
      arrhythmias. The investigators propose to study the relation and interaction between gut
      microbiome and ventricular arrhythmogenesis.
Specific Aims:

      Aim 1: To identify specific gut microbiome characteristics of patients who are prone to
      clinically significant or high burden of ventricular arrhythmias compared with patients with
      similar conventional risk factors and low burden of ventricular arrhythmias.

      Aim 2: To examine changes that occur in the gut microbiome composition after treatment of
      ventricular arrhythmias.

      Research Plan:

      This study will enroll 30 subjects recruited from the electrophysiology device clinic at the
      VA medical center, who are individuals with underlying cardiomyopathy and prone to
      ventricular arrhythmias.

      Out of this cohort, the investigators will identify 2 groups who have different ventricular
      arrhythmia burden despite similar conventional clinical factors.

      This information regarding ventricular arrhythmia burden will be obtained from device
      interrogation at the time of recruitment. Our proposal is study and compare the fecal
      microbial composition of these groups to analyze association with ventricular arrhythmia
      burden. Patients will provide a fecal sample for analysis at the time of enrollment.

      After clinically indicated treatment in the high ventricular arrhythmia group, the
      investigators will retest fecal samples to assess for changes in characteristics after
      treatment. This will be done to study changes in the gut microbiome with ventricular
      arrhythmia in the same individual.

      After initial testing of the high burden group, they will undergo treatment aimed at
      decreasing their burden of arrhythmia, with some combination of anti-arrhythmic drugs,
      sympathetic blockade, or ventricular tachycardia ablation. After demonstrating a period of 3
      months without sustained VT/VF on device interrogation, their fecal samples will be
      re-analyzed. If a patient continues to have VT/VF requiring intermittent device therapies
      despite a 6 month period of intensification of therapy, their fecal sample will be
      re-analyzed after that 6 month timeframe.
observational model: Case-Control
time perspective: Retrospective
measure: Difference in microbial composition of gut microbiome in study and control groups
time frame: 1 year
description: Microbial components identified through genetics will be compared between groups.
measure: Change in microbial composition of gut microbiome after successful VT therapy
time frame: 1 year
description: Microbial components identified through genetics will be compared before and after VT therapy in the high VT burden group.
arm group label: High Ventricular Arrhythmia burden group
description: Inclusion criteria for all groups:
age >18 years-old
competent and willing to provide consent
presence of implantable cardioverter-defibrillator
diagnosis of cardiomyopathy
left ventricular ejection fraction of 35% or less as assessed by echocardiogram within 1 year prior to enrollment
Inclusion criteria for high ventricular arrhythmia burden group:
• at least one episode of sustained VT/VF or VT/VF requiring ICD therapies within the preceding 3 months as assessed on device interrogation at the time of study enrollment
Both groups will have stool sample collected for microbial analysis. This is anticipated twice for the high ventricular arrhythmia (VA) burden group. Once at the time of diagnosis of VA and later after the clinically indicated treatment for the VA.
arm group label: Control group
description: Inclusion criteria for all groups:
age >18 years-old
competent and willing to provide consent
presence of implantable cardioverter-defibrillator
diagnosis of cardiomyopathy
left ventricular ejection fraction of 35% or less as assessed by echocardiogram within 1 year prior to enrollment
Inclusion criteria for control group:
• no VT/VF on device interrogation for a period of at least 3 months preceding study enrollment
Both groups will have stool sample collected for microbial analysis. This is anticipated only once for the control group.
intervention type: Diagnostic Test
intervention name: Stool test for microbial analysis
description: Fecal samples will be analyzed by shotgun metagenomics and sample from the high ventricular arrhythmia burden will be compared with those from comparable control patients with low ventricular arrhythmia burden.
arm group label: Control group
arm group label: High Ventricular Arrhythmia burden group
Stool samples will be collected and analyzed for bacterial DNA analysis to characterize
      nature and function of microbial flora. Host human DNA may be a contaminant
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Ramil Goel, MD
role: Principal Investigator
affiliation: Malcolm Randall VAMC
last name: Ramil Goel, MD
phone: 7165533752
email: ramilgoel@hotmail.com
facility: 
status: Recruiting
contact: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: North Florida Foundation for Research and Education
investigator full name: Ramil Goel
investigator title: Clinical Electrophysiologist, Malcolm Randall VAMC, Gainesville
mesh term: Arrhythmias, Cardiac
mesh term: Tachycardia
mesh term: Tachycardia, Ventricular
mesh term: Ventricular Fibrillation
sharing ipd: No