Effect of Vivomixx® on Neuroinflammation in Patients Withs Cirrhosis

Sponsor

Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau (Other)

Overall Status

Withdrawn

CT.gov ID

NCT03236090

Collaborator

Spanish Clinical Research Network - SCReN (Other)

Enrollment

Location

Arms

7.8

Actual Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
Cirrhosis, Liver	Dietary Supplement: Vivomixx	N/A

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

Study Design

Study Type:

Interventional

Actual Enrollment :

0 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Decompensated patients with cirrhosis: Outpatients with refractory ascites (substudy 1) (n=20) Patients hospitalized because bacterial infection (substudy 2) (n=30)Decompensated patients with cirrhosis:Outpatients with refractory ascites (substudy 1) (n=20) Patients hospitalized because bacterial infection (substudy 2) (n=30)

Masking:

Single (Participant)

Masking Description:

Placebo (we evaluate the probiotic Vivomixx® vs placebo as adjunctive in addition to the standard of care)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Jul 15, 2017

Actual Primary Completion Date :

Mar 9, 2018

Actual Study Completion Date :

Mar 9, 2018

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Outpatients with refractory ascites 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 Vivomixx®sachets containing 450 x 109 bacteria, 2 every 12 hours (n=25), or placebo (n=25)
Active Comparator: Patients hospitalized because bacterial infection 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 Vivomixx®sachets containing 450 x 109 bacteria, 2 every 12 hours (n=25), or placebo (n=25)

Arm

Intervention/Treatment

Active Comparator: Outpatients with refractory ascites

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

Vivomixx®sachets containing 450 x 109 bacteria, 2 every 12 hours (n=25), or placebo (n=25)

Active Comparator: Patients hospitalized because bacterial infection

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

Vivomixx®sachets containing 450 x 109 bacteria, 2 every 12 hours (n=25), or placebo (n=25)

Outcome Measures

Primary Outcome Measures

Change in neuroinflammation [Change from baseline at 30 days]
For substudy 1, neuroinflammation will be measured by MRI at baseline and 30 days
Change in neuroinflammation [Change from baseline at 3 days]
For substudy 2, neuroinflammation will be measured by MRI at baseline and 3 days

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.