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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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ClinicalTrials.gov Identifier: NCT02484573
Recruitment Status : Recruiting
First Posted : June 29, 2015
Last Update Posted : January 31, 2019
Sponsor:
Information provided by (Responsible Party):
ALDO TORRE DELGADILLO, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran

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 Not Applicable

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 39 participants
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 2015
Estimated Primary Completion Date : January 2020
Estimated Study Completion Date : August 2020


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 Name: Inderalici




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.



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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02484573


Contacts
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Contact: Aldo Torre Delgadillo, MD 525554870900 detoal@yahoo.com
Contact: Jonathan Manuel Aguirre Valadez, MD 525554870900 yanomani@hotmail.com

Locations
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Mexico
Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran Recruiting
Mexico City, Mexico, 14000
Contact: Aldo Torre Delgadillo, M.D. M.Sc    54870900 ext 2711    detoal@yahoo.com   
Principal Investigator: Aldo Torre-Delgadillo, MD         
Sponsors and Collaborators
Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
Investigators
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Principal Investigator: Aldo Torre, MD INCMNSZ

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Responsible Party: ALDO TORRE DELGADILLO, MD, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
ClinicalTrials.gov Identifier: NCT02484573     History of Changes
Other Study ID Numbers: GAS-1116-14/15-1
First Posted: June 29, 2015    Key Record Dates
Last Update Posted: January 31, 2019
Last Verified: January 2019
Keywords provided by ALDO TORRE DELGADILLO, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran:
Cirrhosis
Variceal Bleeding
Non-selective beta blocker
Intestinal Permeability
Gene expression
Bacterial translocation
Additional relevant MeSH terms:
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Propranolol
Liver Cirrhosis
Fibrosis
Pathologic Processes
Liver Diseases
Digestive System Diseases
Adrenergic beta-Antagonists
Adrenergic Antagonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Anti-Arrhythmia Agents
Antihypertensive Agents
Vasodilator Agents