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

Primary Purpose

Liver Cirrhoses

Status
Unknown status
Phase
Not Applicable
Locations
Mexico
Study Type
Interventional
Intervention
Propanolol
Sponsored by
Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Liver Cirrhoses focused on measuring Cirrhosis, Variceal Bleeding, Non-selective beta blocker, Intestinal Permeability, Gene expression, Bacterial translocation

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept 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)

Sites / Locations

  • Instituto Nacional de Ciencias Medicas y Nutricion Salvador ZubiranRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Propanolol

Arm Description

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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.
Serum inflammatory markers
Compare serum proinflammatory cytokines and lipopolysaccharide levels in patients with cirrhosis before and after treatment with propranolol for 1 month.

Full Information

First Posted
June 16, 2015
Last Updated
January 29, 2019
Sponsor
Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
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1. Study Identification

Unique Protocol Identification Number
NCT02484573
Brief Title
Evaluation of Intestinal Permeability in Cirrhotic Patients Before and After Treatment With Non-selective Beta Blocker (Propranolol)
Official Title
Evaluation of Intestinal Permeability in Cirrhotic Patients Before and After Treatment With Non-selective Beta Blocker (Propranolol)
Study Type
Interventional

2. Study Status

Record Verification Date
January 2019
Overall Recruitment Status
Unknown status
Study Start Date
May 2015 (undefined)
Primary Completion Date
January 2020 (Anticipated)
Study Completion Date
August 2020 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran

4. Oversight

Data Monitoring Committee
No

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Liver Cirrhoses
Keywords
Cirrhosis, Variceal Bleeding, Non-selective beta blocker, Intestinal Permeability, Gene expression, Bacterial translocation

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
39 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Propanolol
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Propanolol
Other Intervention Name(s)
Inderalici
Primary Outcome Measure Information:
Title
Intestinal permeability
Description
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.
Time Frame
Baseline and after 4 weeks of propranolol treatment
Secondary Outcome Measure Information:
Title
Expression of genes related to intestinal mucosal integrity
Description
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.
Time Frame
Baseline and after 4 weeks of propranolol treatment
Title
Presence of intercellular junction proteins by immunohistochemistry
Description
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.
Time Frame
Baseline and after 4 weeks of propranolol treatment
Title
Serum inflammatory markers
Description
Compare serum proinflammatory cytokines and lipopolysaccharide levels in patients with cirrhosis before and after treatment with propranolol for 1 month.
Time Frame
Baseline and after 4 weeks of propranolol treatment

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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)
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Aldo Torre Delgadillo, MD
Phone
525554870900
Email
detoal@yahoo.com
First Name & Middle Initial & Last Name or Official Title & Degree
Jonathan Manuel Aguirre Valadez, MD
Phone
525554870900
Email
yanomani@hotmail.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Aldo Torre, MD
Organizational Affiliation
INCMNSZ
Official's Role
Principal Investigator
Facility Information:
Facility Name
Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
City
Mexico City
ZIP/Postal Code
14000
Country
Mexico
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Aldo Torre Delgadillo, M.D. M.Sc
Phone
54870900
Ext
2711
Email
detoal@yahoo.com
First Name & Middle Initial & Last Name & Degree
Aldo Torre-Delgadillo, MD

12. IPD Sharing Statement

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

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