Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Oral Gut Liver Axis in Cirrhosis

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03030820
Recruitment Status : Completed
First Posted : January 25, 2017
Last Update Posted : April 4, 2018
Sponsor:
Information provided by (Responsible Party):
Virginia Commonwealth University

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Cirrhosis Periodontitis Gingivitis Procedure: Dental Cleaning Not Applicable

Detailed Description:

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

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 44 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: Oral Gut Liver Axis in Cirrhosis
Study Start Date : October 2016
Actual Primary Completion Date : March 2018
Actual Study Completion Date : March 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Cirrhosis

Arm Intervention/treatment
Experimental: Dental cleaning
Patients with cirrhosis and healthy controls will undergo dental examination and subsequent dental cleaning if necessary.
Procedure: Dental Cleaning
This is standard of care dental cleaning as is guided by the initial dental evaluation




Primary Outcome Measures :
  1. Change in serum endotoxin [ Time Frame: 30 days ]
    Relative change in serum endotoxin levels using LAL (limulus amebocyte lysate) assay will be measured before/after cleaning and between groups


Secondary Outcome Measures :
  1. Change in performance on two batteries of Cognitive function [ Time Frame: 30 days ]
    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

  2. Change in systemic inflammatory cytokines in the blood [ Time Frame: 30 days ]
    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

  3. All-cause Hospitalizations [ Time Frame: 3 months ]
    All-cause, liver-related and elective hospitalizations at 3 months will be studied and compared between groups

  4. Change in microbiota composition in the saliva and stool [ Time Frame: 30 days ]
    Relative change in microbial composition using 16SrRNA multi-tagged sequencing in stool and saliva will be measured before/after cleaning and between groups

  5. MELD (model for end-stage liver disease) score change in the cirrhosis group [ Time Frame: 30 days ]
    Relative change in MELD score will be analyzed in cirrhotic patients before/after cleaning

  6. Quality of life changes [ Time Frame: 30 days ]
    Changes in quality of life using Sickness Impact Profile will be measured



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   21 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion criteria:

Cirrhotic subjects:

  1. Age 21-75 years
  2. Able to give informed consent
  3. Cirrhosis diagnosed using biopsy or suggestive radiological features or endoscopic evidence of varices in a subject with chronic liver disease

Healthy controls:

  1. Age 21-75 years
  2. Able to give informed consent
  3. Without chronic diseases

Exclusion Criteria:

Exclusions for all subjects (will be done at the screening visit at both clinics)

  1. Current use of absorbable antibiotics (use of antibiotics within 4 weeks)
  2. Diagnosed with severe chronic or aggressive forms of periodontitis based on American Academy of Periodontology Classification (5)
  3. Presence of more than 2 severe cavitated caries lesions
  4. Presence of oral soft-tissue lesions such as ulcers
  5. Presence of abscesses
  6. Unclear diagnosis of cirrhosis (for cirrhotics)
  7. Edentulous or less than 20 natural teeth
  8. Smoking, oral tobacco and alcohol abuse within 3 months
  9. Prisoners
  10. Pregnant women
  11. INR(international normalized ratio) >1.5
  12. Platelet count <50,000
  13. Diagnosed bleeding disorders
  14. Patients on anti-coagulation
  15. Patients who will otherwise be eligible for prophylactic antibiotics before dental cleaning
  16. Last dental cleaning within 3 months of study.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03030820


Locations
Layout table for location information
United States, Virginia
Virginia Commonwealth University
Richmond, Virginia, United States, 23298
Sponsors and Collaborators
Virginia Commonwealth University
Investigators
Layout table for investigator information
Principal Investigator: Jasmohan Bajaj, MD VCU medical Center
Layout table for additonal information
Responsible Party: Virginia Commonwealth University
ClinicalTrials.gov Identifier: NCT03030820    
Other Study ID Numbers: HM20006081
First Posted: January 25, 2017    Key Record Dates
Last Update Posted: April 4, 2018
Last Verified: April 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by Virginia Commonwealth University:
cirrhosis
Periodontitis
oral health
gingivitis
inflammation
Additional relevant MeSH terms:
Layout table for MeSH terms
Liver Cirrhosis
Periodontitis
Gingivitis
Fibrosis
Pathologic Processes
Liver Diseases
Digestive System Diseases
Periodontal Diseases
Mouth Diseases
Stomatognathic Diseases
Gingival Diseases