Evaluation of Intestinal Permeability in Cirrhotic Patients Before and After Treatment With Non-selective Beta Blocker (Propranolol)

Study Overview
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Brief Summary
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This study seeks to investigate whether non-selective beta blocker treatment decreases intestinal permeability in cirrhotic patients by altering the expression of genes encoding intercellular junction proteins.

Detailed Description
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There is evidence that the non-selective beta-blocker (NSBB) propranolol reduces intestinal permeability and decreases bacterial translocation in cirrhotic patients, independent of hemodynamic effects on portal pressure. The mechanism by which this decrease in intestinal permeability and bacterial translocation occurs has not been established. Among the proposed mechanisms are: modification of splanchnic hemodynamics, increased gastrointestinal motility, and immunological properties of nonselective beta blockade. It is not known, however, if beta-blocker treatment decreases intestinal permeability by altering the expression of genes encoding intercellular junction proteins. This study seeks to investigate this question to improve understanding of the mechanism by which beta-blockers work in primary and secondary prophylaxis of variceal hemorrhage.

Official Title
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Evaluation of Intestinal Permeability in Cirrhotic Patients Before and After Treatment With Non-selective Beta Blocker (Propranolol)

Conditions
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Liver Cirrhoses

Intervention / Treatment
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* Drug: Propanolol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: > 18 years Diagnosis of cirrhosis of any etiology or severity as established by the treating physician (biopsy, biochemical, imaging) High risk gastroesophageal varices, that is those with medium/large varices or any size varices with red wale signs Scheduled appointment for endoscopic ligation as previously ordered by the treating physician Signed informed consent Ability to keep return appointments Exclusion Criteria: Beta blocker treatment within 1 month prior to study period Antibiotic treatment during or within 1 month prior to study period Prebiotic or probiotic treatment during or within 1 month before study period Current immunosuppressive treatment Patients with active infectious process Patients with portal thrombosis Patients with hepatocellular carcinoma Patients with intestinal surgical shunts Patients with chronic diarrhea or documented celiac disease Patients with chronic renal failure (KDOQI: ≤ 3) Patients with allergy or absolute contraindication for the use of nonselective beta blockers (asthma, significant heart block, systolic BP <90 mm Hg, basal HR <55, refractory ascites)

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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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Propanolol<br>Patients will take the non-selective beta blocker propranolol for approximately 4 weeks starting immediately after endoscopy for esophageal variceal ligation. Patients will be initiated on a dose of 20mg by mouth every 12 hrs before titration to maximum tolerated dose. Patients will undergo testing before and after treatment for the variables listed in the outcomes section below. | Drug: Propanolol<br> <br> * Other names: Inderalici;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Intestinal permeability | Evaluate and compare intestinal permeability using studies evaluating the absorption of three orally administered sugars (sucrose, mannitol and lactulose) in patients with cirrhosis before and after treatment with propranolol for 1 month. | Baseline and after 4 weeks of propranolol treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Expression of genes related to intestinal mucosal integrity | Evaluate and compare the expression of mRNA of the genes for zona occludens 1 (ZO1), occludin, claudin-1 and 2 in gastric and duodenal mucosal tissue of patients with cirrhosis, before and after treatment with propranolol for 1 month. | Baseline and after 4 weeks of propranolol treatment | 
| Presence of intercellular junction proteins by immunohistochemistry | Evaluate and compare the presence of intercellular junction proteins by immunohistochemistry in gastric and duodenal mucosa of patients with cirrhosis before and after treatment with propranolol for 1 month. | Baseline and after 4 weeks of propranolol treatment | 
| Serum inflammatory markers | Compare serum proinflammatory cytokines and lipopolysaccharide levels in patients with cirrhosis before and after treatment with propranolol for 1 month. | Baseline and after 4 weeks of propranolol treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cirrhosis, Variceal Bleeding, Non-selective beta blocker, Intestinal Permeability, Gene expression, Bacterial translocation