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The Effect of Probiotics (VSL) on Portal Hypertension

Sponsor
University of Alberta (Other)
Overall Status
Completed
CT.gov ID
NCT01032941
Collaborator
(none)
18
Enrollment
1
Location
2
Arms
18
Duration (Months)
1
Patients Per Site Per Month

Study Details

Study Description

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
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hypertension (VIP study) to determine whether this agent would have beneficial effects in portal pressure reduction (unpublished data Tandon, P. et al.).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 Design

Study Type:
Interventional
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 :
Dec 1, 2009
Actual Primary Completion Date :
Jun 1, 2011
Actual Study Completion Date :
Jun 1, 2011

Arms and Interventions

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

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Reduction in portal pressure [12 months]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 80 Years
    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 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

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Puneeta Tandon, Assistant Professor, University of Alberta
    ClinicalTrials.gov Identifier:
    NCT01032941
    Other Study ID Numbers:
    • VSL3PHTNUoA
    First Posted:
    Dec 16, 2009
    Last Update Posted:
    Jan 20, 2012
    Last Verified:
    Jan 1, 2012
    Keywords provided by Puneeta Tandon, Assistant Professor, University of Alberta
    Portal Hypertension
    Portal Pressure Measurement
    VSL3
    Cirrhosis
    End Stage Liver Disease
    Probiotics
    Additional relevant MeSH terms:
    Hypertension, Portal
    Hypertension

    Study Results

    No Results Posted as of Jan 20, 2012