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

Sponsor

Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran (Other)

Overall Status

Unknown status

CT.gov ID

NCT02484573

Collaborator

(none)

Enrollment

Location

Arm

Duration (Months)

0.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Liver Cirrhoses	Drug: Propanolol	N/A

Detailed Description

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

39 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

May 1, 2015

Anticipated Primary Completion Date :

Jan 1, 2020

Anticipated Study Completion Date :

Aug 1, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Propanolol 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 Other Names: Inderalici

Arm

Intervention/Treatment

Experimental: Propanolol

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

Other Names:

Inderalici

Outcome Measures

Primary Outcome Measures

Intestinal permeability [Baseline and after 4 weeks of propranolol treatment]
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.

Secondary Outcome Measures

Expression of genes related to intestinal mucosal integrity [Baseline and after 4 weeks of propranolol treatment]
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.
Presence of intercellular junction proteins by immunohistochemistry [Baseline and after 4 weeks of propranolol treatment]
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.
Serum inflammatory markers [Baseline and after 4 weeks of propranolol treatment]
Compare serum proinflammatory cytokines and lipopolysaccharide levels in patients with cirrhosis before and after treatment with propranolol for 1 month.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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)