Safety and Efficacy of a Probiotic Supplement in IBS-D

This is a double-blind, randomised, placebo-controlled trial designed to assess the safety and efficacy of a single probiotic strain on symptom severity in adults with IBS-D, when consumed orally in capsule form once daily for 84 days. Volunteers will be screened in order to identify up to 134 participants meeting ROME IV criteria for IBS-D. The study will involve 5 visits over a total of 105 days [visit 1: screening, commencement of run in period (-21 to -14 days), visit 2: baseline/ randomisation (day 0), visits 3 and 4: intervention period (day 28 ± 2, day 56 ± 2), visit 5: end of study (day 84± 2)]. Participants will fill in daily and weekly eDiaries, and questionnaires will be administered at study visits. Faecal samples will be collected on visits 2 and 5.

Inclusion criteria

• Males and females aged ≥18 to ≤ 65 years.
• Participants diagnosed with diarrhoea-predominant irritable bowel syndrome (IBS-D) as per ROME IV criteria:

i) Recurrent abdominal pain on average at least one day/week in the last three months, associated with two or more of the following criteria:

• Related to defecation
• Associated with a change in stool frequency (increase/decrease in frequency).
• Associated with a change in the form (appearance) of stool. ii) History of abnormal bowel movements predominantly diarrhoea (>25% of bowel movements categorised as stool form type 6 or 7 (diarrhoea) and <25% as stool form type 1 or 2 (constipation) on BSFS).
• Participants with an IBS-SSS score ≥ 175.
• Participants who test negative for COVID-19 by Rapid Antigen Test Device.
• Participants who did not change their diet within three months before the screening day and are willing to sustain that diet during the study.
• Participants who can comply and perform the procedures as per the protocol (consumption of study products, biological sample collection procedures, and study visit schedule).
• Participants who are literate enough to understand the purpose of the study and their rights.
• Participants who are able to give written informed consent and are willing to participate in the study.

Exclusion criteria

• Participants who score ≥ 40 in either the 'state' or 'trait' section of the STAI-AD questionnaire (both sections to be assessed).
• Participants diagnosed with Coeliac Disease.
• Lactose intolerant participants unless on a strict lactose free diet for at least three months before screening day with persistent symptoms of IBS-D.
• Participants with a body mass index (BMI) ≥ 30 kg/m2.
• Presence of uncontrolled hypertension defined as systolic blood pressure (SBP) ≥ 140 mm Hg and/or diastolic blood pressure (DBP) ≥ 90 mm Hg.
• Participants with a history of intake of antibiotics (Rifaximin, metronidazole, or any other), other probiotics, prebiotics, synbiotics, food supplements with iron or calcium, peppermint oil, acid sequestrants (cholestyramine, Bile colestipol), introduced/active low FODMAP diet, and histamine H2-receptor antagonists/H2 blockers within six weeks prior to the screening day.
• Participants with a history of daily intake of antidepressants (Tricyclic antidepressants, Selective serotonin reuptake inhibitors (SSRIs), and Selective serotonin-norepinephrine reuptake Inhibitors (SSNRIs)), clonidine, otilonium bromide, asimadoline, eluxadoline, diphenoxylate, antispasmodics including mebeverine and pinnaverium and anticholinergics within two weeks prior to the screening day.
• Participants with a history of bariatric surgery or surgical resection of the stomach, small intestine, or large intestine.
• Participants with a history of gastrointestinal-related abdominal surgery other than hernia repair.
• Participants with a history of or complications from inflammatory bowel disease (Crohn's disease or ulcerative colitis) and ischemic colitis.
• Participants showing signs of bile acid malabsorption (BAM), as evident from the history of green colour or foul odour of the stool during the last month.
• Participants with a history of or complications from GI malignant tumours.
• Participants with a history of or complications from other malignant tumours in the last 5 years.
• History of any significant neurological and psychiatric condition which may affect the participation and inference of the study's endpoints.
• Participation in other clinical studies in the last 90 days prior to screening day.
• Active smokers or using any form of smokeless tobacco.
• Participants with substance abuse problems (within two years) defined as:

• Use of recreational drugs (such as cocaine, methamphetamine, marijuana, etc.)/Nicotine dependence.
• High-risk drinking as defined by the consumption of four or more alcohol-containing beverages on any day or eight or more alcohol-containing beverages per week for women and five or more alcohol-containing beverages on any day or 15 or more alcohol-containing beverages per week for men.
• Participants having clinically significant illnesses of cardiovascular, endocrine, immune, respiratory, hepato-biliary, kidney and urinary, haematological, musculoskeletal system and/or any inflammatory disorder and other gastrointestinal diseases.
• Participants with active human immunodeficiency virus (HIV) or hepatitis A, B or C infection.
• Female participants being pregnant, breastfeeding or planning pregnancy in the course of the study.
• Any condition that could, in the opinion of the Investigator, preclude the participant's ability to successfully and safely complete the study or that may confound study outcomes.