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

January 29, 2019 updated by: ALDO TORRE DELGADILLO, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Anticipated)

39

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Aldo Torre Delgadillo, MD
  • Phone Number: 525554870900
  • Email: detoal@yahoo.com

Study Contact Backup

Study Locations

  • Mexico
      • Mexico City, Mexico, 14000
        • Recruiting
        • Instituto Nacional de Ciencias Medicas y Nutrición Salvador Zubirán
        • Contact:
          • Aldo Torre Delgadillo, M.D. M.Sc
          • Phone Number: 2711 54870900
          • Email: detoal@yahoo.com
        • Principal Investigator:
          • Aldo Torre-Delgadillo, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Intestinal permeability
Time Frame: 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.
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
Time Frame: 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.
Baseline and after 4 weeks of propranolol treatment
Presence of intercellular junction proteins by immunohistochemistry
Time Frame: 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.
Baseline and after 4 weeks of propranolol treatment
Serum inflammatory markers
Time Frame: 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.
Baseline and after 4 weeks of propranolol treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran

Investigators

  • Principal Investigator: Aldo Torre, MD, INCMNSZ

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2015

Primary Completion (Anticipated)

January 1, 2020

Study Completion (Anticipated)

August 1, 2020

Study Registration Dates

First Submitted

June 16, 2015

First Submitted That Met QC Criteria

June 24, 2015

First Posted (Estimate)

June 29, 2015

Study Record Updates

Last Update Posted (Actual)

January 31, 2019

Last Update Submitted That Met QC Criteria

January 29, 2019

Last Verified

January 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • GAS-1116-14/15-1

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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