Saccharomyces Boulardii CNCM I-745 on Intestinal Barrier Function

This placebo-controlled parallel group clinical study in healthy adults from the general population aims to investigate whether oral supplementation with S. boulardii CNCM I-745 could strengthen the intestinal barrier function and counteract the acute NSAID-induced hyperpermeability. Indomethacin will be used short term to increase intestinal permeability. The primary objective of the study is to assess the effects of S. boulardii CNCM I-745 on this impaired intestinal permeability.

Inclusion criteria

• Considered as healthy after a comprehensive clinical assessment (detailed medical history and complete physical examination).
• With a body mass index (BMI) comprised between 18 and 35 kg/m^2 and weight > 50 kg at Screening.
• Able to comply with study requirements and to provide signed informed consent.
• Has signed the informed consent form before beginning any study procedure.
• Regular defecation (frequency and stool consistency, with at least about three bowel movements a week).
• For women of childbearing potential:

• A negative urine pregnancy test immediately prior to starting the study treatment;
• Agreement to comply with approved methods of contraception during the whole study: unless they meet the criteria of post-menopausal; i.e., 12 months of spontaneous amenorrhea, women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, including women whose career, lifestyle, or sexual orientation precludes intercourse with a male partner, should use one or more of the following acceptable methods of contraception that should be maintained throughout the study:
• Surgical sterilization;
• Hormonal contraception (implantable, patch, oral, intra-muscular);
• Intra-uterine device;
• Double barrier method (diaphragm plus condom);
• At the discretion of the investigator, total abstinence is acceptable in cases where age, career, lifestyle, or sexual orientation of the patient ensures compliance.

Exclusion criteria

• History of hypersensitivity to the study treatments (active substance or excipients), brewer's or baker's yeast.
• Contraindication and special warning to the study treatments according to the Summary of Product Characteristics (SmPCs).
• History of chronic constipation with passage of fewer than 3 spontaneous bowel movements per week on average.
• History of chronic or recurrent diarrhea with spontaneous unformed bowel movements equivalent to or more often than 3 times daily.
• Prior gastrointestinal surgery (apart from appendectomy or cholecystectomy performed at least more than one year ago).
• History of Clostridium difficile infection.
• Active gastrointestinal disease.
• Known chronic or recurrent systemic disorder (including diabetes and hypertension) that may interfere with the study treatment evaluation.
• Associated immune deficiency.
• Severe hepatic or renal impairment.
• Clinically relevant abnormalities in results of laboratory tests as per Investigator's judgement.
• Patients with a central venous catheter.
• Oral or systemic antibacterial therapy during the 3 months prior to study enrollment.
• NSAIDs and proton pump inhibitor treatment longer than 1 week, within 3 months prior to study enrollment.
• Steroids within 6 weeks prior to study enrollment.
• Use of medications affecting gastrointestinal transit or permeability within 7 days prior to the testing.
• Use of artificial sweeteners, lactulose, mannitol within 2 days prior to the testing and during the 24 h testing period.
• New prescription medications during the 2 weeks prior to study enrollment.
• Use of probiotics or drugs that alters gut microbiota or function, during 4 weeks prior to study enrollment.
• Intake of antifungals within 14 days prior to study enrollment.
• Substantial changes in eating habits within 30 days prior to receiving the first dose of IMP product, as assessed by the Investigator.
• Current smoker.
• History or presence of drug or alcohol abuse.
• Inability to abstain from intensive muscular effort the day before the intestinal permeability test.
• Breast-feeding woman.
• Patients enrolled in another clinical trial within the past 30 days.
• Patients not able to fill in the study questionnaires.
• Any condition or personal circumstance that, in the opinion of the investigator, renders the subject unlikely or unable to comply with the full study protocol.