The Effect of Probiotics (VSL) on Portal Hypertension

A Randomized Controlled Trial on the Beneficial Effects of Probiotics on Portal Hemodynamics in Decompensated Cirrhotic Patients

The investigators will address the hypothesis that portal hypertension is mediated in part by bacterial or endotoxin translocation and the production of inflammatory mediators (tumor necrosis factor-α (TNFα), etc.). The investigators hypothesize that food supplementation with the probiotic product VSL#3 in patients with Child Pugh B/C cirrhosis will have a beneficial effect on in portal pressure (as measured by the HVPG) by reducing inflammatory mediators and improving systemic and splanchnic hemodynamics.

Study Overview

• Status: Completed
• Conditions: Portal Hypertension
• Intervention / Treatment: Drug: Probiotic

Detailed Description

We have recently completed an open-label uncontrolled trial of the probiotic VSL#3 in 8 patients with compensated cirrhosis and evidence of portal hypertension (VIP study) to determine whether this agent would have beneficial effects in portal pressure reduction (unpublished data Tandon, P. et al.). The open label design and the inclusion of compensated (Child Pugh A) cirrhotic patients in this initial study were chosen to confirm the safety and tolerance of VSL#3 and the safety of the portal pressure measurements at our center. No changes of physical status occured. There was a non-significant reduction in portal pressure from 19.7 to 18.1 mm Hg after 2 months of VSL#3 supplementation. Furthermore, there was a significant reduction in the serum aldosterone level (p=0.03). IL-8 levels were reduced in 4/6 patients analyzed to date. These results suggest that VSL#3 results in cytokine reduction and an improvement in the effective circulating volume even in these well-compensated cirrhotic patients. The comparison of the rest of the pro-inflammatory mediators and stool microflora is still being analyzed.

The data in our initial study is very promising. As our patients were compensated cirrhotics with normal intestinal permeability and only mild baseline perturbations in hepatic function parameters (INR, bilirubin, albumin) and neurohormonal markers (aldosterone, renin), it is not surprising that a reduction in portal pressure was not identified. Consistent with previous studies however, these local results confirm the safety and tolerance of both VSL#3 as well as portal pressure measurements in cirrhotic patients (20,24,25).

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 2C8
      • University of Alberta

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age 18-80
• Cirrhosis
• Childs-Pugh Class B/C

Exclusion Criteria:

• Bacterial infection
• Grade 3-4 hepatic encephalopathy
• GI bleeding in the past 2 weeks
• Hepatocellular carcinoma beyond the Milan criteria
• Transjugular intrahepatic portosystemic shunt (TIPS), surgical shunt
• Portal vein thrombosis
• Antibiotics in the past 2 weeks
• Myocardial infarction, stroke or life-threatening arrhythmia within the last 6 months
• Active alcohol or illicit drug use
• Failure to consent to the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: HEALTH_SERVICES_RESEARCH
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo; Patients in this group will be given placebo 2 packets BID for 8 weeks.	Drug: Probiotic; Patients in this group will be given the probiotic VSL#3 2 packets BID for a total of 8 weeks.; Other Names: VSL#3
EXPERIMENTAL: VSL#3; Patients in this group will be given 2 packets of VSL#3 BID for 8 weeks.	Drug: Probiotic; Patients in this group will be given the probiotic VSL#3 2 packets BID for a total of 8 weeks.; Other Names: VSL#3

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Reduction in portal pressure	12 months

Collaborators and Investigators

• Sponsor: University of Alberta
• Investigators: Principal Investigator: Puneeta Tandon, MD, FRCPC, MSc, University of Alberta; Principal Investigator: Vince Bain, MD, FRCPC, University of Alberta

Study record dates

Study Major Dates

• Study Start: December 1, 2009
• Primary Completion (ACTUAL): June 1, 2011
• Study Completion (ACTUAL): June 1, 2011

Study Registration Dates

• First Submitted: December 3, 2009
• First Submitted That Met QC Criteria: December 15, 2009
• First Posted (ESTIMATE): December 16, 2009

Study Record Updates

• Last Update Posted (ESTIMATE): January 20, 2012
• Last Update Submitted That Met QC Criteria: January 18, 2012
• Last Verified: January 1, 2012

More Information

Terms related to this study

• Keywords: Probiotics; Cirrhosis; Portal Hypertension; End Stage Liver Disease; VSL3; Portal Pressure Measurement
• Additional Relevant MeSH Terms: Digestive System Diseases; Cardiovascular Diseases; Vascular Diseases; Liver Diseases; Hypertension; Hypertension, Portal
• Other Study ID Numbers: VSL3PHTNUoA