The Effect of Probiotics (VSL) on Portal Hypertension

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hypertension (VIP study) to determine whether this agent would have beneficial effects in portal pressure reduction (unpublished data Tandon, P. et al.).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

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

Conditions
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Portal Hypertension

Intervention / Treatment
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* Drug: Probiotic


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Health Services Research
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Patients in this group will be given placebo 2 packets BID for 8 weeks. | Drug: Probiotic<br>* Patients in this group will be given the probiotic VSL#3 2 packets BID for a total of 8 weeks.<br>* Other names: VSL#3;|
| Experimental: VSL#3<br>Patients in this group will be given 2 packets of VSL#3 BID for 8 weeks. | Drug: Probiotic<br>* Patients in this group will be given the probiotic VSL#3 2 packets BID for a total of 8 weeks.<br>* Other names: VSL#3;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reduction in portal pressure |  | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Portal Hypertension, Portal Pressure Measurement, VSL3, Cirrhosis, End Stage Liver Disease, Probiotics