Periodontal Therapy and Oral-gut-hepatic Axis Cirrhosis: a Randomized Controlled Trial
Primary Purpose
Periodontal Diseases, Cirrhosis
Status
Unknown status
Phase
Not Applicable
Locations
India
Study Type
Interventional
Intervention
Periodontal therapy
Oral hygiene advice
Sponsored by
About this trial
This is an interventional treatment trial for Periodontal Diseases focused on measuring Periodontitis, Cirrhosis
Eligibility Criteria
Inclusion Criteria:
- Cirrhosis of any etiology
- Aged between 18 Years to 65 Years
- Either gender
- Generalized Stage I & II Periodontitis as defined by the 2017 World Workshop on the Classification of Periodontal and Peri-Implant Diseases and Conditions)
Exclusion Criteria:
- Inability to obtain informed consent from patient or relatives.
- Severe cardiopulmonary disease
- Pregnancy
- HIV infection
- Recent abdominal surgery (with in last 6 months)
- Patient on immunosuppressive drugs
- Malignancies including Hepatocellular carcinoma
- Gastrointestinal (GI bleed) in the last 4 weeks
- Oral antibiotics or antifungals taken in last 2 weeks.
- Active sepsis
- Stage III & IV Periodontitis
- Localized /Molar-incisor pattern
- Patients who received periodontal treatment within the last 6 months
- Patients who require antibiotic prophylaxis before examination or treatment
- Presence of a carious exposed teeth/periapical abscess etc requiring Root Canal Treatment/extraction
Sites / Locations
- Postgraduate Institute of Medical Education and ResearchRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Sham Comparator
Arm Label
Periodontal therapy
Control
Arm Description
Patients offered periodontal therapy in 2-4 sittings (n=40), Dental hygiene advised
Patients given standard medical treatment (n=40), Dental hygiene advised
Outcomes
Primary Outcome Measures
All-cause Hospitalizations
All-cause, liver-related and elective hospitalizations at 3 months
Change in Model for End Stage Liver Disease (MELD) score
Secondary Outcome Measures
Change in systemic inflammatory cytokines in the blood
Full Information
NCT ID
NCT04330469
First Posted
March 23, 2020
Last Updated
September 26, 2021
Sponsor
Postgraduate Institute of Medical Education and Research
1. Study Identification
Unique Protocol Identification Number
NCT04330469
Brief Title
Periodontal Therapy and Oral-gut-hepatic Axis Cirrhosis: a Randomized Controlled Trial
Official Title
Effect of Periodontal Therapy and Modification of Oral-gut-hepatic Axis in Patients With Cirrhosis
Study Type
Interventional
2. Study Status
Record Verification Date
September 2021
Overall Recruitment Status
Unknown status
Study Start Date
March 1, 2020 (Actual)
Primary Completion Date
December 30, 2022 (Anticipated)
Study Completion Date
December 30, 2022 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Postgraduate Institute of Medical Education and Research
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
Periodontitis is common in patients with cirrhosis and may lead to systemic sepsis. 1 Grønkjær et al demonstrated that severe periodontitis predicted higher mortality in patients with cirrhosis. 2 In India, the wide use of oral tobacco, smoking and poor dental hygiene fosters a dual hit to the outcomes of liver disease especially in the setting of liver transplantation. However, a causal relationship between the oral microbiome and liver disease and outcomes is a matter of conjecture. Oral bacterial diseases, such as caries and periodontitis are caused by a consortium of bacteria rather than a single species. These constitute opportunistic infections that occur under the proper circumstances and conditions, e.g., diet, host immune response, complicating systemic or genetic disorders, pH, poor oral hygiene and lifestyle. It is well known that specific bacterial taxa that colonize the oral cavity are associated with oral health and oral diseases or afflictions, such as dental caries, periodontal diseases, endodontic lesions, dry socket, halitosis, and odontogenic infections.
Bajaj et al have demonstrated systematic periodontal therapy in cirrhotic outpatients improved endotoxemia, as well as systemic and local inflammation, and modulated salivary and stool microbial dysbiosis over 30 days. Bajaj et al performed another study on comparison of oral and gut microbiota in patients with and without hepatic encephalopathy.
There were differences in salivary microbiota composition and inflammatory markers between controls and cirrhotics. The association between periodontitis, oral dysbiosis and the prognosis of cirrhosis remains crucial with relevance to situations like acute-on-chronic liver failure and other inflammation-related adverse events.
Detailed Description
The aim of this study is to prospectively determine the association of generalised Stage I & II (initial to moderate) with all-cause and cirrhosis-related mortality in patients with cirrhosis. We also plan to evaluate the oral microbiome and association of oral dysbiosis with complications of cirrhosis to assess if early treatment by dental interventions may improve nutrition and outcomes in cirrhosis. Lastly this prospective randomized controlled trial will provide insight into whether manipulation of the oral microbiome by dental procedures and oral hygiene training, antibiotics- local and systemic, use of probiotics etc can alter adverse outcomes, nutrition and health related quality of life in cirrhosis.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Periodontal Diseases, Cirrhosis
Keywords
Periodontitis, Cirrhosis
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
80 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Periodontal therapy
Arm Type
Experimental
Arm Description
Patients offered periodontal therapy in 2-4 sittings (n=40), Dental hygiene advised
Arm Title
Control
Arm Type
Sham Comparator
Arm Description
Patients given standard medical treatment (n=40), Dental hygiene advised
Intervention Type
Procedure
Intervention Name(s)
Periodontal therapy
Intervention Description
Treatment will be performed by a periodontist.
Intensive removal of subgingival and supragingival calculus and plaque biofilm by scaling, root-planing and polishing. The procedures will be carried out with the use of hand scalers and a piezoelectric ultrasonic scaler with universal tips. Disclosing solution will be used to visualize the plaque for the clinician.
One to four sessions of subgingival scaling and root planing by quadrant, under local anesthesia as may be deemed necessary during the study period.
Subgingival irrigation using an antiseptic mouth rinse (chlorhexidine 0.12%).
Polishing of the coronal and radicular surfaces of the teeth.
Intervention Type
Procedure
Intervention Name(s)
Oral hygiene advice
Intervention Description
Oral hygiene advised by Periodontist
Primary Outcome Measure Information:
Title
All-cause Hospitalizations
Description
All-cause, liver-related and elective hospitalizations at 3 months
Time Frame
90days
Title
Change in Model for End Stage Liver Disease (MELD) score
Time Frame
90 days
Secondary Outcome Measure Information:
Title
Change in systemic inflammatory cytokines in the blood
Time Frame
90 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Cirrhosis of any etiology
Aged between 18 Years to 65 Years
Either gender
Generalized Stage I & II Periodontitis as defined by the 2017 World Workshop on the Classification of Periodontal and Peri-Implant Diseases and Conditions)
Exclusion Criteria:
Inability to obtain informed consent from patient or relatives.
Severe cardiopulmonary disease
Pregnancy
HIV infection
Recent abdominal surgery (with in last 6 months)
Patient on immunosuppressive drugs
Malignancies including Hepatocellular carcinoma
Gastrointestinal (GI bleed) in the last 4 weeks
Oral antibiotics or antifungals taken in last 2 weeks.
Active sepsis
Stage III & IV Periodontitis
Localized /Molar-incisor pattern
Patients who received periodontal treatment within the last 6 months
Patients who require antibiotic prophylaxis before examination or treatment
Presence of a carious exposed teeth/periapical abscess etc requiring Root Canal Treatment/extraction
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Madhumita Premkumar, DM
Phone
01722756344
Email
drmadhumitap@gmail.com
First Name & Middle Initial & Last Name or Official Title & Degree
Shipra Gupta, MDS
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Madhumita Premkumar, DM
Organizational Affiliation
Postgraduate Institute of Medical Education and Research
Official's Role
Principal Investigator
Facility Information:
Facility Name
Postgraduate Institute of Medical Education and Research
City
Chandigarh
ZIP/Postal Code
160012
Country
India
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Madhumita PREMKUMAR, DM
12. IPD Sharing Statement
Citations:
PubMed Identifier
31336404
Citation
Costa FO, Lages EJP, Lages EMB, Cota LOM. Periodontitis in individuals with liver cirrhosis: A case-control study. J Clin Periodontol. 2019 Oct;46(10):991-998. doi: 10.1111/jcpe.13172. Epub 2019 Aug 28.
Results Reference
background
PubMed Identifier
29439734
Citation
Gronkjaer LL, Holmstrup P, Schou S, Kongstad J, Jepsen P, Vilstrup H. Periodontitis in patients with cirrhosis: a cross-sectional study. BMC Oral Health. 2018 Feb 13;18(1):22. doi: 10.1186/s12903-018-0487-5.
Results Reference
background
PubMed Identifier
31049117
Citation
Hanioka T, Morita M, Yamamoto T, Inagaki K, Wang PL, Ito H, Morozumi T, Takeshita T, Suzuki N, Shigeishi H, Sugiyama M, Ohta K, Nagao T, Hanada N, Ojima M, Ogawa H. Smoking and periodontal microorganisms. Jpn Dent Sci Rev. 2019 Nov;55(1):88-94. doi: 10.1016/j.jdsr.2019.03.002. Epub 2019 Apr 24.
Results Reference
background
PubMed Identifier
22054477
Citation
Helenius-Hietala J, Meurman JH, Hockerstedt K, Lindqvist C, Isoniemi H. Effect of the aetiology and severity of liver disease on oral health and dental treatment prior to transplantation. Transpl Int. 2012 Feb;25(2):158-65. doi: 10.1111/j.1432-2277.2011.01381.x. Epub 2011 Nov 5.
Results Reference
background
PubMed Identifier
23607641
Citation
Aberg F, Helenius-Hietala J, Meurman J, Isoniemi H. Association between dental infections and the clinical course of chronic liver disease. Hepatol Res. 2014 Mar;44(3):349-53. doi: 10.1111/hepr.12126. Epub 2013 Apr 29.
Results Reference
background
PubMed Identifier
27219464
Citation
Krishnan K, Chen T, Paster BJ. A practical guide to the oral microbiome and its relation to health and disease. Oral Dis. 2017 Apr;23(3):276-286. doi: 10.1111/odi.12509. Epub 2016 Jul 4.
Results Reference
background
PubMed Identifier
30118351
Citation
Bajaj JS, Matin P, White MB, Fagan A, Deeb JG, Acharya C, Dalmet SS, Sikaroodi M, Gillevet PM, Sahingur SE. Periodontal therapy favorably modulates the oral-gut-hepatic axis in cirrhosis. Am J Physiol Gastrointest Liver Physiol. 2018 Nov 1;315(5):G824-G837. doi: 10.1152/ajpgi.00230.2018. Epub 2018 Aug 17.
Results Reference
background
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Periodontal Therapy and Oral-gut-hepatic Axis Cirrhosis: a Randomized Controlled Trial
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