L. Reuteri DSM 17938 and L. Reuteri ATCC PTA 6475 in Moderate to Severe Irritable Bowel in Adults
Condition: Irritable Bowel Syndrome
MeSH terms: Irritable Bowel Syndrome; Syndrome
Study type: Interventional

Summary: 
      Randomized, double blind, controlled clinical trial, to evaluate safety and efficacy of L.
      reuteri DSM 17938 and L. reuteri ATCC PTA 6475 as adjuvant to reduce the severity of symptoms
      in adults with moderate to severe irritable bowel syndrome (IBS). Primary outcome: Global
      clinical Improve assessed by the GSRS-IBS score. Adults 18-65 years, any gender, with ROME IV
      criteria for moderate to severe IBS and body max index <36 will be included. Prescreening
      will be run for 2 weeks, the intervention period will be 2/days for 14t weeks, follow by a 2
      weeks period of observation with no intervention. Secondary outcomes include: a) Improvements
      in the stool patterns evaluated through Bristol Stool Form (BSF); b) Improvement of the
      quality of life (QoL) measured by Latin-American IBS-QoL questionnaire; c) Improvement of the
      depression and anxiety severity evaluated by the Goldberg Depression and Anxiety Scale; d)
      Frequency of rescue medication use and e) Frequency of Adverse Events (AEs)
    

Detailed description: 
      Rationale: Irritable bowel syndrome (IBS) is the most commonly diagnosed functional
      gastrointestinal disorder observed in older children and adults. It is a frequent cause of
      chronic abdominal pain and changed bowel habits. Produce a significant negative effect on
      quality of life and it is associated with a significant economic burden disease con total
      expenditures in USA exceeding $20 billion/year. Since 2008 different clinical trials and
      meta-analysis had been published about the safety and efficacy of the use of probiotics in
      adults with IBS. In LATAM evidence about this topic is scarce.

      Primary outcome: Global Clinical Improvement assessed by the GSRS-IBS score (Spanish/LA
      version) Secondary/Exploratory outcomes: Improvements in the Bristol Stool Form (BSF),
      Quality of Life (QoL) improvement assessed by Latin-American IBS-QoL questionnaire, Goldberg
      scale depression and Anxiety scale, Frequency of rescue medication use andSecondary adverse
      events Clinical design: Randomized, double blind, controlled clinical trial, with two arms
      Type of patients: Age 18-65 years, any gender, ROME IV diagnostic criteria for IBS (Recurrent
      abdominal pain, on average, at least 1 day per week in the last 3 months, associated with 2
      or more of the following criteria a) Related to defecation, b) Associated with a change in
      frequency of stool, c) Associated with a change in form (appearance) of stool and/or d)
      Criteria fulfilled for the last 3 months with symptom onset at least 6 months before
      diagnosis), with a baseline GSRS-IBS score (Spanish/LA version) moderate to severe IBS, body
      mass index (BMI 25 to 35 (Mild to moderate obesity) and signed Informed consent.

      Subject Information and Consent: All subjects will receive written and verbal information
      regarding the study at Visit 1. This information will emphasise that participation in the
      study is voluntary and that the subject may withdraw from the study at any time and for any
      reason. All subjects will be given the opportunity to ask questions about the study and will
      be given sufficient time to decide whether to participate in the study. Before any
      study-related procedures, the informed consent form will be signed and personally dated by
      the subject and by the person who conducted the informed consent discussion. A copy of the
      subject information including the signed consent form will be provided to the subject.

      Interventions: 2 weeks run in, 14 weeks' treatment and 2 weeks follow up. L. reuteri Gastrus
      (L. reuteri DSM 17938 and L. reuteri ATCC PTA 6475) at dose of 2x108 Colony Forming Units
      (CFU). One chewable tablet is to be taken twice per day (one in the morning and one in the
      afternoon) giving a total daily dose of at least 4x108 CFU/day. The placebo will have
      identical ingredients except for lacking the bacteria. One chewable tablet is to be taken
      twice per day (one in the morning and one in the afternoon). The study products shall be kept
      refrigerated (+20C - +80C) during the study. Randomization will be performed by Sponsor
      Labelling will be performed in Research centres by independent pharmacist or similar person
      not involved in the study.

      Study logistics: After informed consent, subjects must to fill a 2-week pre-randomization
      form to be sure they fill the criteria for IBS and define severity. If the patient fulfils
      all inclusion and none of the exclusion criteria the patient will be randomized to one of the
      two treatment groups. According to the randomization groups the patient will receive the
      corresponding blinded study product. The patient will be standardized to take the research
      product twice per day for 14 weeks, and complete the GSRS-IBS (Spanish/LA version) and the
      BSF on a daily basis, the Latin-American IBS-QoL questionnaire, the Goldberg depression and
      anxiety scale once, a diet history (2 days/week) and the report of adverse events. A basal
      faecal sample will be obtained in a subsample of patients to ultra-freeze and measure in a
      second-time microbiota by pyroseq and faecal calprotectin (At the end of treatment). At the
      end of treatment subjects will be evaluated according to primary and secondary/exploratory
      outcomes and they will be invited for a third periods, for 2 weeks with no intervention to
      evaluate the same clinical parameters.
    

Intervention name(s): L. reuteri DSM 17938 and L. reuteri ATCC PTA 6475; Placebo
Intervention type(s): Dietary Supplement; Dietary Supplement
Intervention description(s): L. reuteri Gastrus (L. reuteri DSM 17938 and L. reuteri ATCC PTA 6475) at dose of 2x108 Colony Forming Units (CFU) per tablet. One chewable tablet is to be taken twice per day (one in the morning and one in the afternoon) giving a total daily dose of at least 4x108 CFU/day.; Placebo
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Randomized, double blind, controlled clinical trial, with two branches. Randomization will be centralized performed by sponsor. L. reuteri Gastrus at dose of 2x108 Colony Forming Units (CFU) or placebo will be adminsitrated twice per day
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: irritable bowel syndrome, adults, L. reuteri