Effect of Vivomixx® on Neuroinflammation in Patients Withs Cirrhosis

Study Overview
=================
Brief Summary
-----------------
Study Design: Double-blind randomized placebo-controlled clinical trial Study Duration: 2 years Study Center: Single center Hospital de la Santa Creu i Sant Pau, Barcelona Objectives: To assess the effect of Vivomixx® on neuroinflammation and systemic inflammatory response in patients with cirrhosis

Detailed Description
-----------------
Study variables Main variables Neuroinflammation Systemic inflammatory response Secondary variables Cognitive function Bacterial translocation Intestinal barrier Systemic oxidative damage Time until SBP or other bacterial infection resolution in patients with infections Incidence of complications of cirrhosis and mortality during the study 40 patients, 20 and 30 in each of the two substudies, respectively Diagnosis and Main Inclusion Criteria Decompensated patients with cirrhosis: Outpatients with refractory ascites (substudy 1) (n=20) Patients hospitalized because bacterial infection (substudy 2) (n=30) Study Product: Vivomixx®sachets containing 450 x 109 bacteria, 2 every 12 hours (n=25), or placebo (n=25) Duration of administration: 30 days Follow up The following patients' assessments will be performed: in substudy 1 at baseline and at the end of the treatment (30 days), and in substudy 2 at baseline, on day 1, day 2, day 3, day 7, at infection resolution, and at discharge or day 30. Clinical and analytical assessments will be performed every three months after the end of the study Comparator Placebo (we evaluate the probiotic Vivomixx® vs placebo as adjunctive in addition to the standard of care) Statistical Methodology Fisher's exact test for categorical variables and Student's t test and Mann-Whitney and Wilcoxon tests for quantitative variables. Correlations will be assessed by Spearman test. A two-sided p value <0.05 will be considered statistically significant

Official Title
-----------------
Study of the Effect of Vivomixx® on Neuroinflammation Ans Systemic Inflammatory Response in Patients With Cirrhosis

Conditions
-----------------
Cirrhosis, Liver

Intervention / Treatment
-----------------
* Dietary Supplement: Vivomixx


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Outpatients with cirrhosis and refractory ascites according to current definition (29) (substudy 1), and hospitalized patients with cirrhosis and an episode of bacterial infection (substudy 2) at Hospital de la Santa Creu i Sant Pau. Cirrhosis will be diagnosed by clinical, analytical and ultrasonographic findings or by liver biopsy. SBP will be diagnosed by an ascitic fluid neutrophil count > 250/mm3 with or without positive culture (28). Bacteremia, urinary infections, pneumonia, cellulitis, other bacterial infections and possible or suspected infections will be diagnosed according to current guidelines (13,14,28). All patients with SBP, bacteremia or pneumonia will be included. However patients with urinary infections, cellulitis or suspected infection these non-SBP infections will be required to fulfil the following requirements: at least two criteria of SIRS (systemic inflammatory response syndrome) (Annex I) (30) and CRP (C-reactive protein) >= 10 mg/dl (28). Exclusion Criteria: Advanced hepatocellular carcinoma (beyond Milan's criteria) or any other malignancy determining a poor short-term prognosis. Advanced liver insufficiency [MELD (model for end-stage liver disease) >25]. Marked symptomatic comorbidities (neurological, cardiac, pulmonary, renal, psychiatric, HIV infection). Septic shock, ileus, need for tracheal intubation or intensive care unit. Immunomodulatory drugs. In substudy 1, any infection at inclusion in the study.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Decompensated patients with cirrhosis: Outpatients with refractory ascites (substudy 1) (n=20) Patients hospitalized because bacterial infection (substudy 2) (n=30)
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Outpatients with refractory ascites<br>20 consecutive outpatients with cirrhosis and refractory ascites Vivomixx®sachets containing 450 x 109 bacteria, 2 every 12 hours (n=25), or placebo (n=25) | Dietary Supplement: Vivomixx<br>* Vivomixx®sachets containing 450 x 109 bacteria, 2 every 12 hours (n=25), or placebo (n=25)<br>|
| Active Comparator: Patients hospitalized because bacterial infection<br>30 consecutive patients with cirrhosis and bacterial infections. All patients will receive endovenous antibiotics and, only in the case of patients with SBP, also intravenous albumin Vivomixx®sachets containing 450 x 109 bacteria, 2 every 12 hours (n=25), or placebo (n=25) | Dietary Supplement: Vivomixx<br>* Vivomixx®sachets containing 450 x 109 bacteria, 2 every 12 hours (n=25), or placebo (n=25)<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in neuroinflammation | For substudy 1, neuroinflammation will be measured by MRI at baseline and 30 days | Change from baseline at 30 days | 
| Change in neuroinflammation | For substudy 2, neuroinflammation will be measured by MRI at baseline and 3 days | Change from baseline at 3 days | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Systemic inflammation, Cognitive function, Bacterial translocation, Cirrhosis, Probiotics, neuroinflammation