Effect of Vivomixx® on Neuroinflammation in Patients Withs Cirrhosis

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

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

Study Overview

• Status: Withdrawn
• Conditions: Cirrhosis, Liver
• Intervention / Treatment: Dietary supplement: Vivomixx

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:

  1. Outpatients with refractory ascites (substudy 1) (n=20)
  2. 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 Type: Interventional
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Spain
  • Barcelona, Spain, 08025
    • Hospital de la Santa Creu i Sant Pau

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / 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)

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

Collaborators and Investigators

• Sponsor: Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau
• Collaborators: Spanish Clinical Research Network - SCReN

Study record dates

Study Major Dates

• Study Start (Actual): July 15, 2017
• Primary Completion (Actual): March 9, 2018
• Study Completion (Actual): March 9, 2018

Study Registration Dates

• First Submitted: June 29, 2017
• First Submitted That Met QC Criteria: July 31, 2017
• First Posted (Actual): August 1, 2017

Study Record Updates

• Last Update Posted (Actual): March 13, 2018
• Last Update Submitted That Met QC Criteria: March 12, 2018
• Last Verified: March 1, 2018

More Information

Terms related to this study

• Keywords: Probiotics; Systemic inflammation; Cognitive function; Cirrhosis; Bacterial translocation; neuroinflammation
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Liver Diseases; Fibrosis; Liver Cirrhosis
• Other Study ID Numbers: IIBSP-VIV-2016-109

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No