Clinical trial NCT02484573: 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
Overall status: UNKNOWN
Phase: NA
Conditions: Liver Cirrhoses
Keywords: Cirrhosis
Variceal Bleeding
Non-selective beta blocker
Intestinal Permeability
Gene expression
Bacterial translocation
Lead sponsor: Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
Sponsor class: OTHER
First posted: 2015-06-29
Enrollment: 39
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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)

Primary outcomes:
measure: Intestinal permeability
timeFrame: Baseline and after 4 weeks of propranolol treatment
Secondary outcomes:
measure: Expression of genes related to intestinal mucosal integrity
timeFrame: Baseline and after 4 weeks of propranolol treatment
measure: Presence of intercellular junction proteins by immunohistochemistry
timeFrame: Baseline and after 4 weeks of propranolol treatment
measure: Serum inflammatory markers
timeFrame: Baseline and after 4 weeks of propranolol treatment
Other outcomes:
Locations:
city: Mexico City
country: Mexico
facility: Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
Study officials:
affiliation: INCMNSZ
name: Aldo Torre, MD
role: PRINCIPAL_INVESTIGATOR
References: