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

Liver Cirrhoses Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02484573
• Other study ID #: GAS-1116-14/15-1
• Status: Recruiting
• Phase: N/A
• Start date: May 2015
• Est. completion date: August 2020

Study information

• Verified date: January 2019
• Source: Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
• Contact: Aldo Torre Delgadillo, MD
• Phone: 525554870900
• Email: detoal[@]yahoo.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 39
• Est. completion date: August 2020
• Est. primary completion date: January 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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)

Related Conditions & MeSH terms

• Fibrosis
• Liver Cirrhoses
• Liver Cirrhosis

Intervention

Drug:
• Propanolol

Locations

Country	Name	City	State
Mexico	Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran	Mexico City

Sponsors (1)

Lead Sponsor	Collaborator
Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran

Country where clinical trial is conducted

Mexico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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