Text Size

The Effect of Probiotics (VSL) on Portal Hypertension

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Puneeta Tandon, University of Alberta
ClinicalTrials.gov Identifier:
NCT01032941
First received: December 3, 2009
Last updated: January 18, 2012
Last verified: January 2012
History of Changes
  Purpose

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 Intervention Phase
Portal Hypertension
 Drug: Probiotic
 Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by University of Alberta:

Primary Outcome Measures:
  • Reduction in portal pressure [ Time Frame: 12 months ] [ Designated as safety issue: No ]

Enrollment: 18
Study Start Date: December 2009
Study Completion Date: June 2011
Primary Completion Date: June 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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).

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01032941

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

No publications provided

Responsible Party: Puneeta Tandon, Assistant Professor, University of Alberta
ClinicalTrials.gov Identifier: NCT01032941     History of Changes
Other Study ID Numbers: VSL3PHTNUoA
Study First Received: December 3, 2009
Last Updated: January 18, 2012
Health Authority: Canada: Health Canada

Keywords provided by University of Alberta:
Portal Hypertension
Portal Pressure Measurement
VSL3
 Cirrhosis
End Stage Liver Disease
Probiotics

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

ClinicalTrials.gov processed this record on May 16, 2013