The Effect of Probiotics (VSL) on Portal Hypertension

NCT ID: NCT01032941

Last Updated: 2012-01-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 18 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-12-31
• Study Completion Date: 2011-06-30

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.

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hypertension (VIP study) to determine whether this agent would have beneficial effects in portal pressure reduction (unpublished data Tandon, P. et al.).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

Conditions

Portal Hypertension

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: HEALTH_SERVICES_RESEARCH
• Blinding Strategy: TRIPLE

Study Groups

Placebo

Patients in this group will be given placebo 2 packets BID for 8 weeks.

Group Type: PLACEBO_COMPARATOR

Probiotic

Intervention Type: DRUG

Patients in this group will be given the probiotic VSL#3 2 packets BID for a total of 8 weeks.

VSL#3

Patients in this group will be given 2 packets of VSL#3 BID for 8 weeks.

Group Type: EXPERIMENTAL

Probiotic

Intervention Type: DRUG

Patients in this group will be given the probiotic VSL#3 2 packets BID for a total of 8 weeks.

Interventions

Probiotic

Patients in this group will be given the probiotic VSL#3 2 packets BID for a total of 8 weeks.

Intervention Type: DRUG

Other Intervention Names

VSL#3

Eligibility 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

University of Alberta

OTHER

Sponsor Role: lead

Responsible Party

Puneeta Tandon

Assistant Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Puneeta Tandon, MD, FRCPC, MSc

Role: PRINCIPAL_INVESTIGATOR

University of Alberta

Vince Bain, MD, FRCPC

Role: PRINCIPAL_INVESTIGATOR

University of Alberta

Locations

University of Alberta

Edmonton, Alberta, Canada

Countries

Canada

Other Identifiers

VSL3PHTNUoA

Identifier Type: -

Identifier Source: org_study_id