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Effect of Vivomixx® on Neuroinflammation in Patients Withs Cirrhosis

Primary Purpose

Cirrhosis, Liver

Status

Withdrawn

Phase

Not Applicable

Locations

Spain

Study Type

Interventional

Intervention

Vivomixx

About this trial

This is an interventional treatment trial for Cirrhosis, Liver focused on measuring Cirrhosis, Probiotics, Systemic inflammation, neuroinflammation, Cognitive function, Bacterial translocation

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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.

Sites / Locations

Hospital de la Santa Creu i Sant Pau

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Arm Label

Outpatients with refractory ascites

Patients hospitalized because bacterial infection

Arm Description

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)

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)

Outcomes

Primary Outcome Measures

Change in neuroinflammation

For substudy 1, neuroinflammation will be measured by MRI at baseline and 30 days

Change in neuroinflammation

For substudy 2, neuroinflammation will be measured by MRI at baseline and 3 days

Secondary Outcome Measures

Full Information

NCT ID

NCT03236090

First Posted

June 29, 2017

Last Updated

March 12, 2018

Sponsor

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

Collaborators

Spanish Clinical Research Network - SCReN

1. Study Identification

Unique Protocol Identification Number

NCT03236090

Brief Title

Effect of Vivomixx® on Neuroinflammation in Patients Withs Cirrhosis

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

March 2018

Overall Recruitment Status

Withdrawn

Why Stopped

Problems to recruit patients due to exclusion criteria

Study Start Date

July 15, 2017 (Actual)

Primary Completion Date

March 9, 2018 (Actual)

Study Completion Date

March 9, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

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

Collaborators

Spanish Clinical Research Network - SCReN

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

5. 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

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Cirrhosis, Liver

Keywords

Cirrhosis, Probiotics, Systemic inflammation, neuroinflammation, Cognitive function, Bacterial translocation

7. Study Design

Primary Purpose

Treatment

Study Phase

Not Applicable

Interventional Study Model

Parallel Assignment

Model Description

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

Masking

Participant

Masking Description

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

Allocation

Randomized

Enrollment

0 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Outpatients with refractory ascites

Arm Type

Active Comparator

Arm Description

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)

Arm Title

Patients hospitalized because bacterial infection

Arm Type

Active Comparator

Arm Description

Intervention Type

Dietary Supplement

Intervention Name(s)

Vivomixx

Intervention Description

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

Primary Outcome Measure Information:

Title

Change in neuroinflammation

Description

For substudy 1, neuroinflammation will be measured by MRI at baseline and 30 days

Time Frame

Change from baseline at 30 days

Title

Change in neuroinflammation

Description

For substudy 2, neuroinflammation will be measured by MRI at baseline and 3 days

Time Frame

Change from baseline at 3 days

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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.

Facility Information:

Facility Name

Hospital de la Santa Creu i Sant Pau

City

Barcelona

ZIP/Postal Code

08025

Country

Spain

12. IPD Sharing Statement

Plan to Share IPD

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Effect of Vivomixx® on Neuroinflammation in Patients Withs Cirrhosis

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