<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/NCT03030820</url>
  </required_header>
  <id_info>
    <org_study_id>HM20006081</org_study_id>
    <nct_id>NCT03030820</nct_id>
  </id_info>
  <brief_title>Oral Gut Liver Axis in Cirrhosis</brief_title>
  <official_title>Oral Gut Liver Axis in Cirrhosis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Virginia Commonwealth University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Virginia Commonwealth University</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This will be a prospective study of cirrhotics and healthy controls comparing their oral&#xD;
      microbiota, endotoxemia and systemic inflammation at baseline and at 30 days after clinically&#xD;
      indicated systematic oral cleansing and interventions as well as 3-month hospitalizations&#xD;
      post-cleaning.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This will be a prospective study of cirrhotics and healthy controls comparing their oral&#xD;
      microbiota, endotoxemia and systemic inflammation at baseline and at 10 and 30 days after&#xD;
      clinically indicated systematic oral cleansing and interventions as well as 3-month&#xD;
      hospitalizations post-cleaning.&#xD;
&#xD;
      The investigators will recruit cirrhotic subjects and age- matched healthy controls from the&#xD;
      hepatology clinics. Subjects will be informed regarding the study and will give the&#xD;
      investigators a written informed consent.&#xD;
&#xD;
      After informed consent and evaluation of eligibility, subjects will be asked to complete an&#xD;
      oral health questionnaire and sample collection during the recruitment visit. Patients will&#xD;
      then be scheduled for a dental exam during a separate screening visit up to 7 days after this&#xD;
      recruitment visit at the Dental Clinics.&#xD;
&#xD;
      At this time patients will undergo cognitive testing consisting of a validated cognitive&#xD;
      battery of PHES (psychometric hepatic encephalopathy score) and EncephalApp stroop. In&#xD;
      addition, they will undergo Sickness Impact Profile (a quality of life questionnaire).&#xD;
&#xD;
      During dental exam which will be done during screening visit, the subject will undergo&#xD;
      comprehensive oral evaluation which will include dental xrays (as needed) which are part of&#xD;
      the study, periodontal examination (determination of pocket depth, clinical attachment&#xD;
      levels, bleeding on probing, plaque index) and recording of caries and oral soft tissue&#xD;
      lesions. Dental cleaning is part of the study protocol and not intended to fully treat the&#xD;
      patient's periodontal and dental diseases. Therefore no follow-up dental visits will be&#xD;
      scheduled in the dental clinics after completion of dental cleansing.&#xD;
&#xD;
      The patients who do not qualify for the study will be informed of the findings by the dental&#xD;
      professionals and subsequently the patients need to make arrangements for their dental&#xD;
      treatment needs.&#xD;
&#xD;
      The study will include cirrhotic patients with/without hepatic encephalopathy. Subjects will&#xD;
      then be scheduled for dental cleaning which could occur over 1 or 2 visits as determined&#xD;
      during the screening exam.&#xD;
&#xD;
      Before the initiation of oral therapy, plaque and gingival crevicular samples will be&#xD;
      collected for microbiota. The subjects will receive deep dental cleanings (scaling and root&#xD;
      planing) and oral hygiene instructions as per clinical indication.&#xD;
&#xD;
      Subjects will then be followed at day 10 for clinical exam and day 30 at which point stool,&#xD;
      saliva and blood samples for the similar analyses as before will be collected. There will be&#xD;
      no more dental examinations after the initial assessment and treatment. We will repeat the&#xD;
      cognitive testing at day 30 using alternate forms of the same cognitive tests and also repeat&#xD;
      quality of life testing at day 30 .&#xD;
&#xD;
      The investigators will also follow them for up to 3 months post-cleaning for hospitalizations&#xD;
      using active chart review and follow-up&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>October 2016</start_date>
  <completion_date type="Actual">March 2018</completion_date>
  <primary_completion_date type="Actual">March 2018</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Prevention</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in serum endotoxin</measure>
    <time_frame>30 days</time_frame>
    <description>Relative change in serum endotoxin levels using LAL (limulus amebocyte lysate) assay will be measured before/after cleaning and between groups</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in performance on two batteries of Cognitive function</measure>
    <time_frame>30 days</time_frame>
    <description>Relative change in PHES battery (total standard deviations above normal performance)and EncephalApp Stroop values (seconds taken) will be measured before/after cleaning and between groups</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in systemic inflammatory cytokines in the blood</measure>
    <time_frame>30 days</time_frame>
    <description>Relative change in pg/ml of serum IL-6 (interleukin), IL-1b (interleukin) using ELISA assays will be measured before/after cleaning and between groups</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>All-cause Hospitalizations</measure>
    <time_frame>3 months</time_frame>
    <description>All-cause, liver-related and elective hospitalizations at 3 months will be studied and compared between groups</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in microbiota composition in the saliva and stool</measure>
    <time_frame>30 days</time_frame>
    <description>Relative change in microbial composition using 16SrRNA multi-tagged sequencing in stool and saliva will be measured before/after cleaning and between groups</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>MELD (model for end-stage liver disease) score change in the cirrhosis group</measure>
    <time_frame>30 days</time_frame>
    <description>Relative change in MELD score will be analyzed in cirrhotic patients before/after cleaning</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of life changes</measure>
    <time_frame>30 days</time_frame>
    <description>Changes in quality of life using Sickness Impact Profile will be measured</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">44</enrollment>
  <condition>Cirrhosis</condition>
  <condition>Periodontitis</condition>
  <condition>Gingivitis</condition>
  <arm_group>
    <arm_group_label>Dental cleaning</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients with cirrhosis and healthy controls will undergo dental examination and subsequent dental cleaning if necessary.</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Dental Cleaning</intervention_name>
    <description>This is standard of care dental cleaning as is guided by the initial dental evaluation</description>
    <arm_group_label>Dental cleaning</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion criteria:&#xD;
&#xD;
        Cirrhotic subjects:&#xD;
&#xD;
          1. Age 21-75 years&#xD;
&#xD;
          2. Able to give informed consent&#xD;
&#xD;
          3. Cirrhosis diagnosed using biopsy or suggestive radiological features or endoscopic&#xD;
             evidence of varices in a subject with chronic liver disease&#xD;
&#xD;
        Healthy controls:&#xD;
&#xD;
          1. Age 21-75 years&#xD;
&#xD;
          2. Able to give informed consent&#xD;
&#xD;
          3. Without chronic diseases&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Exclusions for all subjects (will be done at the screening visit at both clinics)&#xD;
&#xD;
          1. Current use of absorbable antibiotics (use of antibiotics within 4 weeks)&#xD;
&#xD;
          2. Diagnosed with severe chronic or aggressive forms of periodontitis based on American&#xD;
             Academy of Periodontology Classification (5)&#xD;
&#xD;
          3. Presence of more than 2 severe cavitated caries lesions&#xD;
&#xD;
          4. Presence of oral soft-tissue lesions such as ulcers&#xD;
&#xD;
          5. Presence of abscesses&#xD;
&#xD;
          6. Unclear diagnosis of cirrhosis (for cirrhotics)&#xD;
&#xD;
          7. Edentulous or less than 20 natural teeth&#xD;
&#xD;
          8. Smoking, oral tobacco and alcohol abuse within 3 months&#xD;
&#xD;
          9. Prisoners&#xD;
&#xD;
         10. Pregnant women&#xD;
&#xD;
         11. INR(international normalized ratio) &gt;1.5&#xD;
&#xD;
         12. Platelet count &lt;50,000&#xD;
&#xD;
         13. Diagnosed bleeding disorders&#xD;
&#xD;
         14. Patients on anti-coagulation&#xD;
&#xD;
         15. Patients who will otherwise be eligible for prophylactic antibiotics before dental&#xD;
             cleaning&#xD;
&#xD;
         16. Last dental cleaning within 3 months of study.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>21 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jasmohan Bajaj, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>VCU medical Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Virginia Commonwealth University</name>
      <address>
        <city>Richmond</city>
        <state>Virginia</state>
        <zip>23298</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>April 2018</verification_date>
  <study_first_submitted>January 5, 2017</study_first_submitted>
  <study_first_submitted_qc>January 20, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 25, 2017</study_first_posted>
  <last_update_submitted>April 2, 2018</last_update_submitted>
  <last_update_submitted_qc>April 2, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">April 4, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>cirrhosis</keyword>
  <keyword>Periodontitis</keyword>
  <keyword>oral health</keyword>
  <keyword>gingivitis</keyword>
  <keyword>inflammation</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Gingivitis</mesh_term>
    <mesh_term>Liver Cirrhosis</mesh_term>
    <mesh_term>Periodontitis</mesh_term>
    <mesh_term>Fibrosis</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/NCT03030820
org study id: HM20006081
nct id: NCT03030820
lead sponsor: 
has dmc: No
This will be a prospective study of cirrhotics and healthy controls comparing their oral
      microbiota, endotoxemia and systemic inflammation at baseline and at 30 days after clinically
      indicated systematic oral cleansing and interventions as well as 3-month hospitalizations
      post-cleaning.
This will be a prospective study of cirrhotics and healthy controls comparing their oral
      microbiota, endotoxemia and systemic inflammation at baseline and at 10 and 30 days after
      clinically indicated systematic oral cleansing and interventions as well as 3-month
      hospitalizations post-cleaning.

      The investigators will recruit cirrhotic subjects and age- matched healthy controls from the
      hepatology clinics. Subjects will be informed regarding the study and will give the
      investigators a written informed consent.

      After informed consent and evaluation of eligibility, subjects will be asked to complete an
      oral health questionnaire and sample collection during the recruitment visit. Patients will
      then be scheduled for a dental exam during a separate screening visit up to 7 days after this
      recruitment visit at the Dental Clinics.

      At this time patients will undergo cognitive testing consisting of a validated cognitive
      battery of PHES (psychometric hepatic encephalopathy score) and EncephalApp stroop. In
      addition, they will undergo Sickness Impact Profile (a quality of life questionnaire).

      During dental exam which will be done during screening visit, the subject will undergo
      comprehensive oral evaluation which will include dental xrays (as needed) which are part of
      the study, periodontal examination (determination of pocket depth, clinical attachment
      levels, bleeding on probing, plaque index) and recording of caries and oral soft tissue
      lesions. Dental cleaning is part of the study protocol and not intended to fully treat the
      patient's periodontal and dental diseases. Therefore no follow-up dental visits will be
      scheduled in the dental clinics after completion of dental cleansing.

      The patients who do not qualify for the study will be informed of the findings by the dental
      professionals and subsequently the patients need to make arrangements for their dental
      treatment needs.

      The study will include cirrhotic patients with/without hepatic encephalopathy. Subjects will
      then be scheduled for dental cleaning which could occur over 1 or 2 visits as determined
      during the screening exam.

      Before the initiation of oral therapy, plaque and gingival crevicular samples will be
      collected for microbiota. The subjects will receive deep dental cleanings (scaling and root
      planing) and oral hygiene instructions as per clinical indication.

      Subjects will then be followed at day 10 for clinical exam and day 30 at which point stool,
      saliva and blood samples for the similar analyses as before will be collected. There will be
      no more dental examinations after the initial assessment and treatment. We will repeat the
      cognitive testing at day 30 using alternate forms of the same cognitive tests and also repeat
      quality of life testing at day 30 .

      The investigators will also follow them for up to 3 months post-cleaning for hospitalizations
      using active chart review and follow-up
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Prevention
masking: None (Open Label)
measure: Change in serum endotoxin
time frame: 30 days
description: Relative change in serum endotoxin levels using LAL (limulus amebocyte lysate) assay will be measured before/after cleaning and between groups
measure: Change in performance on two batteries of Cognitive function
time frame: 30 days
description: Relative change in PHES battery (total standard deviations above normal performance)and EncephalApp Stroop values (seconds taken) will be measured before/after cleaning and between groups
measure: Change in systemic inflammatory cytokines in the blood
time frame: 30 days
description: Relative change in pg/ml of serum IL-6 (interleukin), IL-1b (interleukin) using ELISA assays will be measured before/after cleaning and between groups
measure: All-cause Hospitalizations
time frame: 3 months
description: All-cause, liver-related and elective hospitalizations at 3 months will be studied and compared between groups
measure: Change in microbiota composition in the saliva and stool
time frame: 30 days
description: Relative change in microbial composition using 16SrRNA multi-tagged sequencing in stool and saliva will be measured before/after cleaning and between groups
measure: MELD (model for end-stage liver disease) score change in the cirrhosis group
time frame: 30 days
description: Relative change in MELD score will be analyzed in cirrhotic patients before/after cleaning
measure: Quality of life changes
time frame: 30 days
description: Changes in quality of life using Sickness Impact Profile will be measured
arm group label: Dental cleaning
arm group type: Experimental
description: Patients with cirrhosis and healthy controls will undergo dental examination and subsequent dental cleaning if necessary.
intervention type: Procedure
intervention name: Dental Cleaning
description: This is standard of care dental cleaning as is guided by the initial dental evaluation
arm group label: Dental cleaning
criteria: 
gender: All
minimum age: 21 Years
maximum age: 75 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Jasmohan Bajaj, MD
role: Principal Investigator
affiliation: VCU medical Center
facility: 
country: United States
responsible party type: Sponsor
mesh term: Gingivitis
mesh term: Liver Cirrhosis
mesh term: Periodontitis
mesh term: Fibrosis
sharing ipd: No