The Effect of Probiotics (VSL) on Portal Hypertension

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01032941
Recruitment Status : Completed
First Posted : December 16, 2009
Last Update Posted : January 20, 2012
Information provided by (Responsible Party):
Puneeta Tandon, University of Alberta

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Portal Hypertension Drug: Probiotic Phase 1 Phase 2

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hypertension (VIP study) to determine whether this agent would have beneficial effects in portal pressure reduction (unpublished data Tandon, P. et al.).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  (Clinical Trial)
Actual Enrollment : 18 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Health Services Research
Official Title: A Randomized Controlled Trial on the Beneficial Effects of Probiotics on Portal Hemodynamics in Decompensated Cirrhotic Patients
Study Start Date : December 2009
Actual Primary Completion Date : June 2011
Actual Study Completion Date : June 2011

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 Name: 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 Name: VSL#3

Primary Outcome Measures :
  1. Reduction in portal pressure [ Time Frame: 12 months ]

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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes

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

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 identifier (NCT number): NCT01032941

Canada, Alberta
University of Alberta
Edmonton, Alberta, Canada, T6G 2C8
Sponsors and Collaborators
University of Alberta
Principal Investigator: Puneeta Tandon, MD, FRCPC, MSc University of Alberta
Principal Investigator: Vince Bain, MD, FRCPC University of Alberta

Responsible Party: Puneeta Tandon, Assistant Professor, University of Alberta Identifier: NCT01032941     History of Changes
Other Study ID Numbers: VSL3PHTNUoA
First Posted: December 16, 2009    Key Record Dates
Last Update Posted: January 20, 2012
Last Verified: January 2012

Keywords provided by Puneeta Tandon, University of Alberta:
Portal Hypertension
Portal Pressure Measurement
End Stage Liver Disease

Additional relevant MeSH terms:
Hypertension, Portal
Vascular Diseases
Cardiovascular Diseases
Liver Diseases
Digestive System Diseases