Clinical trial NCT01032941: The Effect of Probiotics (VSL) on Portal Hypertension
Official title: A Randomized Controlled Trial on the Beneficial Effects of Probiotics on Portal Hemodynamics in Decompensated Cirrhotic Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Portal Hypertension
Keywords: Portal Hypertension
Portal Pressure Measurement
VSL3
Cirrhosis
End Stage Liver Disease
Probiotics
Lead sponsor: University of Alberta
Sponsor class: OTHER
First posted: 2009-12-16
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: HEALTH_SERVICES_RESEARCH

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hypertension (VIP study) to determine whether this agent would have beneficial effects in portal pressure reduction (unpublished data Tandon, P. et al.).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

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

Primary outcomes:
measure: Reduction in portal pressure
timeFrame: 12 months
Secondary outcomes:
Other outcomes:
Locations:
city: Edmonton
country: Canada
facility: University of Alberta
state: Alberta
Study officials:
affiliation: University of Alberta
name: Puneeta Tandon, MD, FRCPC, MSc
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Alberta
name: Vince Bain, MD, FRCPC
role: PRINCIPAL_INVESTIGATOR
References: