Effect of Lactibiane Tolerance® to Treat Leaky Gut in Irritable Bowel Syndrome With Predominant Diarrhea (IBS-D)Patients
Condition: IBS - Irritable Bowel Syndrome
MeSH terms: Irritable Bowel Syndrome; Syndrome; Diarrhea
Study type: Interventional

Summary: 
      This is a Phase IV, open-label, single-center, proof-of-concept, pilot study to evaluate the
      effect of Lactibiane Tolerance® in treating leaky gut in IBS-D patients.

      30 consecutive patients with IBS-D and an increased intestinal permeability assessed by
      51Cr-EDTA or 99mTc-DTPA will receive the multistrain probiotic Lactibiane Tolerance® 10
      billion CFU 1 capsule twice a day (30 minutes before breakfast and 30 minutes before dinner)
      for 30 days treatment. At the end of treatment, patients will repeat intestinal permeability
      assessment by 51Cr-EDTA or 99mTc-DTPA.
    

Detailed description: 
      Gut microbiota has many beneficial effects on the GI tract: barrier, immunomodulatory,
      metabolic, trophic among others. Microbiota unbalance or dysbiosis has been associated to
      digestive and extradigestive diseases.

      Irritable bowel syndrome (IBS) is a common chronic disorder that affects the small and large
      intestine which causes cramping, abdominal pain, bloating, gas, diarrhea and/or constipation.
      Only a small number of people with IBS have severe signs and symptoms. Some people can
      control their symptoms by managing diet, lifestyle and stress. Others will need medication
      and counseling.

      Intestinal permeability is the phenomenon of the gut wall in the gastrointestinal tract
      exhibiting permeability. It is a normal function of the intestine to exhibit some
      permeability, to allow nutrients to pass through the gut, while also maintaining a barrier
      function to keep potentially harmful substances (such as antigens) from leaving the intestine
      and migrating to the body more widely. In a healthy human intestine, small particles (< 4 Å
      in radius) can migrate through tight junction claudin pore pathways and particles up to 10-15
      Å (3.5 kDa) can transit through the paracellular space uptake route. One way in which
      intestinal permeability is modulated is via CXCR3 receptors in the gut wall, which respond to
      zonulin. Gliadin (a glycoprotein present in wheat) activates zonulin signaling irrespective
      of the genetic expression of autoimmunity, leading to increased intestinal permeability to
      macromolecules. Bacterial pathogens such as cholera, select enteric viruses, and parasites
      modulate intestinal tight junction structure and function, and these effects may contribute
      to the development of chronic intestinal disorders. Excessive intestinal permeability is a
      factor in stress, infections and in some several autoimmune conditions such as Crohn's
      disease, celiac disease, type 1 diabetes, rheumatoid arthritis, spondyloarthropathies,
      inflammatory bowel disease and irritable bowel syndrome, but it is not clear if increased
      intestinal permeability is a cause or a consequence of these conditions.

      According to its ability to modulate gut associated immune system, to compete with other GI
      bacteria and to increase enterocyte regeneration, probiotic therapy could be proposed to
      overcome an increased intestinal permeability. In particular, preliminary data suggested that
      the probiotic multistrains Lactibiane Tolerance® could be effective in Leaky gut treatment.

      In fact, Nébot-Vivinus et al. demonstrated that Lactibiane Tolerance® could prevent
      epithelial barrier disruption induced by lipopolysaccharide, stress or colonic soluble
      factors from IBS patients and prevent visceral hypersensitivity in experimental models of
      epithelial barrier function.

      Furthermore, Drouault-Holowacz et al. demonstrated that Lactibiane Tolerance® has
      anti-inflammatory properties in vitro by stimulating IL-10 production and in vivo by
      conferring a significant protective effect in the 2,4,6-trinitrobenzene sulfonic acid
      (TNBS)-induced colitis -induced colitis model (more than 50% decrease of colitis symptoms,
      P<0.01).This pilot study has been designed to evaluate the effect of multistrains probiotic
      Lactibiane Tolerance® in a consecutive subset of IBS-D patients with increased Intestinal
      permeability.

      Subject participation in this study will be for approximately 45 days which includes up to a
      2-week screening period and a 30-day treatment period.

      All subjects will participate to the following visits: screening, enrolment, day 15 and day
      30.

      30 IBS-D patients Objectives Primary objective To demonstrate the effect of the multistrain
      probiotic Lactibiane Tolerance® in normalizing leaky gut in IBS-D patients Secondary
      objectives

        -  To characterize the effect of Lactibiane Tolerance® in improving symptoms of IBS

        -  To characterize the effect of Lactibiane Tolerance® on serum levels of zonulin

        -  To characterize the effect of Lactibiane Tolerance® on stool consistency

        -  To characterize the effect of Lactibiane Tolerance® on quality of life

        -  To evaluate the safety and tolerability of Lactibiane Tolerance®. Primary endpoint
           Proportion of subjects with normal intestinal permeability assessed by 51Cr-EDTA or
           99mTc-DTPA after 30 days of treatment.

      Secondary endpoints

        -  Mean variation of scores of items evaluated by VAS-IBS questionnaire after treatment
           compared to baseline

        -  Percentage of patients answering "yes" to the self-evaluation question: "Do you feel
           that your IBS symptoms have been satisfactory alleviated by this treatment?"

        -  Mean concentration of serum zonulin before and after treatment

        -  Mean score on Bristol Stool Scale before and after treatment and proportions of patients
           with 6 and 7 on Bristol Stool scale before and after treatment

        -  Mean score of IBSQoL questionnaire before and after treatment

        -  Safety and tolerability evaluated by the frequency of AEs, SAEs and AEs leading to
           discontinuation of study treatment.
    

Intervention name(s): Multistrain probiotic
Intervention type(s): Dietary Supplement
Intervention description(s): After completion of screening phase, during baseline visit, eligible patients will be assigned to Lactibiane Tolerance® 10 billion CFU 1 capsule twice a day on an empty stomach (30 minutes before breakfast and 30 minutes before dinner).
Other intervention name(s): Lactibiane Tolerance®
Intervention model: Single Group Assignment
Intervention model description: This is a Phase IV, open-label, single-center, proof-of-concept, pilot study to evaluate the effect of Lactibiane Tolerance® in treating leaky gut in IBS-D patients.
Masking: None (Open Label)
Primary purpose: Treatment