A Prospective, Placebo Controlled, Double-Blind, Cross-over Study on the Effects of a Probiotic Preparation (VSL#3) on Metabolic Profile, Intestinal Permeability, Microbiota, Cytokines and Chemokines Expression and Other Inflammatory Markers in Pediatric Patients With Crohn's Disease

This study is currently recruiting participants.
Verified March 2013 by Federico II University
Sponsor:
Information provided by (Responsible Party):
Erasmo Miele, Federico II University
ClinicalTrials.gov Identifier:
NCT01632462
First received: June 25, 2012
Last updated: March 18, 2013
Last verified: March 2013
  Purpose

Background VSL#3 has been reported as an effective adjuvant therapy both in inducing and maintaining remission in pediatric patients affected by Ulcerative Colitis. In addition, it has been shown that VSL#3 is able to modulates barrier function, intestinal permeability, and innate host functions, which if altered, could have a profound impact on the state of colitis. However it is still unclear how VSL#3-induced changes in microbial composition affect the status of intestinal inflammation and no study have investigated the efficacy of VSL#3 in the maintenance of remission in pediatric patients with Crohn's disease (CD).

Objectives The purpose of this study will be to evaluate the effect of a probiotic formulation, VSL#3, versus placebo, on metabolic profile, intestinal permeability, microbiota, cytokines and chemokines expression in pediatric patients with CD in remission of disease. In addition, the efficacy of VSL#3 on the maintenance of remission will be assessed and the safety and the tolerability of the probiotic formula will be evaluated.

Methods This investigation will be a prospective, multicenter, randomized, double-blind, placebo-controlled, cross-over trial. The study will include 50 children affected by CD in remission of disease, as defined by a PCDAI < 10, under treatment with Azathioprine associated or not to 5-ASA and will be articulated in 6 months as follows. All children will be randomised to a treatment group receiving for 2 months either 1-2 packet containing 900 billion bacteria/day of VSL#3 according to their weight, and a group receiving the placebo drug. Assignment to therapy or placebo will be determined according to a computer-generated randomization scheme. At the completion of the 8 weeks, a "wash-out" period of 6 weeks will be done, when no preparation will be administered. Then each patient will be switched to the other group and followed likewise for further 8 weeks. All patients will continue regular medications throughout the study period. A group of 10 volunteer healthy children, comparable in age and sex, will be used as reference group for the analysis of metabolic profile. Patients will be assessed clinically at baseline and every 8 weeks until the completion of the study, at 24 weeks or at the time of relapse. At every visit data will be collected including patient questionnaires regarding disease activity (stool frequency, stool consistency, hematochezia, abdominal pain, extraintestinal manifestations of disease, and overall patient functioning). Additional information collected at the first visit included demographic data, family history, and symptom onset. Physical examination will be performed at each visit by a paediatrician and included an abdominal examination and examination for extraintestinal manifestations of CD. Routine blood tests for CD, cellobiose/mannitol small intestinal permeability study, stool cultures, stool calprotectin, will be performed at every visit and/or at the time of relapse. Urine will be collected for the analysis of metabolic profile with mono and bi-dimensional high-resolution 1H NMR spectroscopy. PCDAI and a physician's global assessment will be used to measure disease activity. At baseline and at 24 weeks the patients will undergo ileocolonoscopy to evaluate and endoscopic and histological activity of disease. Evaluation of microbiota on biopsies and stool samples will be performed at the time of ileocolonoscopies using Fluorescence In Situ Hybridization. Colon biopsies cultures will be performed in order to evaluate cytokines and chemokines patterns by multiplex assay. Additional data will be collected during the study regarding the safety and tolerability of therapy with VSL #3. Statistical analysis will be performed using SPSS version 15 (SPSS Inc, Chicago, Illinois, USA). Variables will be screened for their distribution and appropriate parametric or non parametric tests will be adopted as required. Cross-tabulations will be evaluated by using the Fisher test and χ2test. Statistical significance will be predetermined as P < 0.05.

Expected results The investigators expect to find profound alterations in metabolic profiles, intestinal permeability, microbiota, cytokines and chemokine patterns of patients affected by CD. The administration of VSL#3 is expected to ameliorate all these alterations eventually identified. From a clinical point of view the effects of VSL#3 could be translated in prolonged clinical remission maintenance, offering a new therapeutic tool in the treatment of CD.


Condition Intervention Phase
Crohn's Disease
Drug: VSL#3
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Prospective, Placebo Controlled, Double-Blind, Cross-over Study on the Effects of a Probiotic Preparation (VSL#3) on Metabolic Profile, Intestinal Permeability, Microbiota, Cytokines and Chemokines Expression and Other Inflammatory Markers in Pediatric Patients With Crohn's Disease

Resource links provided by NLM:


Further study details as provided by Federico II University:

Primary Outcome Measures:
  • to evaluate the effect of a probiotic formulation, VSL#3, versus placebo, on metabolic profile, intestinal permeability, microbiota, cytokines and chemokines expression and other inflammatory markers in pediatric patients with Crohn's Disease [ Time Frame: 22 weeks from the enrollment ] [ Designated as safety issue: No ]
    Evaluation of metabolic profile, intestinal permeability, microbiota, cytokines and chemokines expression and other inflammatory markers in pediatric patients with Crohn's before and after the exposure to VSL3 to underline any differences


Secondary Outcome Measures:
  • To determine the effect on Pediatric Crohn Disease Activity Index (PCDAI); [ Time Frame: 8, 14, 22 weeks from the enrollment ] [ Designated as safety issue: Yes ]
  • to determine the time till flare of CD pediatric patients on VSL#3 compared to placebo. [ Time Frame: 8, 14, 22 weeks from the enrollment ] [ Designated as safety issue: No ]

Estimated Enrollment: 30
Study Start Date: September 2012
Estimated Study Completion Date: February 2015
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: VSL#3 arm
15 patients with a diagnosis of Crohn's disease will be exposed to VSL#3 for 8 weeks
Drug: VSL#3
This investigation will be a randomized, double-blind, placebo-controlled, cross-over trial. The study will include 30 children with CD and will be articulated in 6 months as follows. These children will be randomised to a treatment group receiving for 2 months either 1-2 packet containing 900 billion bacteria/day of VSL#3 according to their weight, and a group receiving the placebo drug. Assignment to therapy or placebo will be determined according to a computer-generated randomization scheme.. At the completion of the 8 weeks, a "wash-out" period of 6 weeks will be done, when no preparation will be administered. Then each patient will be switched to the other group and followed likewise for further 8 weeks.
Placebo Comparator: placebo group
15 patients affected by Crohn's disease will be exposed to a placebo for 8 weeks
Drug: VSL#3
This investigation will be a randomized, double-blind, placebo-controlled, cross-over trial. The study will include 30 children with CD and will be articulated in 6 months as follows. These children will be randomised to a treatment group receiving for 2 months either 1-2 packet containing 900 billion bacteria/day of VSL#3 according to their weight, and a group receiving the placebo drug. Assignment to therapy or placebo will be determined according to a computer-generated randomization scheme.. At the completion of the 8 weeks, a "wash-out" period of 6 weeks will be done, when no preparation will be administered. Then each patient will be switched to the other group and followed likewise for further 8 weeks.

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   5 Years to 17 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • diagnosis of CD as defined by clinical, radiological, histological and endoscopic criteria with negative stool culture
  • Males and Females ages 5-17 years
  • Subjects should have CD in remission as defined by a PCDAI < 10
  • Absence of extraintestinal manifestations
  • Patients receiving the following treatment:
  • Azathioprine: if the dose remained constant for 8 weeks prior to the screening visit and had been used continuously for 12 weeks before screening associated or not to 5ASA: if the dose remained constant for 4 weeks before the screening visit and had been used continuously for 8 weeks before screening
  • Written informed consent by parents

Exclusion Criteria:

  • Patients with Ulcerative Colitis (UC)
  • Subjects with documented intestinal stricture, stenosis, obstruction, fistula, abscess, ileostomy
  • Patients with perianal or active CD
  • Treatment with anti-TNFα, ciprofloxacin, metronidazole, systemic corticosteroids, infliximab within 12 weeks of the start of the trial
  • Patients with systemic or intestinal infection
  • Renal, hepatic, haematological, pulmonary, cardiac, neurologic or cerebral diseases
  • Probiotic use in the previous 2 months
  • Inability or unwillingness to give an informed consent
  • Subjects who require outpatient antibiotic therapy.
  • Patients who require surgery for complications related to CD.
  • Concurrent participation in an investigational drug trial
  • Documented history of allergic reaction to Lactobacillus or other probiotic compound
  • Use of Lactobacillus, Bifidobacterium, Enterococcus, Saccharomyces, or any other probiotic bacterial supplement within the past 10 days
  • History of endocarditis, rheumatic valvular disease, congenital cardiac malformations, or cardiac surgery
  • Presence of any other significant medical condition
  • Pregnant or breastfeeding female subjects
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01632462

Contacts
Contact: Erasmo Miele, Assistant professor 00390817464565 erasmo.miele@unina.it

Locations
Italy
University of Naples "Federico II" Recruiting
Naples, Italy, 80131
Contact: Erasmo Miele, Assistant professor    00390816474565    erasmo.miele@unina.it   
Principal Investigator: Erasmo Miele, Assistant Professor         
Sponsors and Collaborators
Federico II University
Investigators
Principal Investigator: Erasmo Miele, Assistant Professor Federico II University
  More Information

Publications:

Responsible Party: Erasmo Miele, Assistant Professor, Federico II University
ClinicalTrials.gov Identifier: NCT01632462     History of Changes
Other Study ID Numbers: 06-2012
Study First Received: June 25, 2012
Last Updated: March 18, 2013
Health Authority: Italy: Ethics Committee

Keywords provided by Federico II University:
Crohn's disease
VSL#3
probiotics
metabolic profile

Additional relevant MeSH terms:
Crohn Disease
Inflammatory Bowel Diseases
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Intestinal Diseases

ClinicalTrials.gov processed this record on April 17, 2014