Periodontal Therapy and Oral-gut-hepatic Axis Cirrhosis: a Randomized Controlled Trial

Study Overview
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Brief Summary
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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
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The aim of this study is to prospectively determine the association of generalised Stage I &amp; 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.

Official Title
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Effect of Periodontal Therapy and Modification of Oral-gut-hepatic Axis in Patients With Cirrhosis

Conditions
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Periodontal Diseases, Cirrhosis

Intervention / Treatment
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* Procedure: Periodontal therapy
* Procedure: Oral hygiene advice


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Periodontal therapy<br>Patients offered periodontal therapy in 2-4 sittings (n=40), Dental hygiene advised | Procedure: Periodontal therapy<br>* 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.<br>|
| Sham Comparator: Control<br>Patients given standard medical treatment (n=40), Dental hygiene advised | Procedure: Oral hygiene advice<br>* Oral hygiene advised by Periodontist<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| All-cause Hospitalizations | All-cause, liver-related and elective hospitalizations at 3 months | 90days | 
| Change in Model for End Stage Liver Disease (MELD) score |  | 90 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in systemic inflammatory cytokines in the blood |  | 90 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Periodontitis, Cirrhosis