Safety and Efficacy of a Probiotic Supplement in IBS-D

Study Overview
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Brief Summary
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This study aims to assess the safety and efficacy of a single probiotic strain on symptom severity in adults with diarrhea-predominant Irritable Bowel Syndrome (IBS-D).

Detailed Description
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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.

Official Title
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Evaluating the Safety and Efficacy of a Probiotic on IBS Symptom Severity in Adults With Diarrhoea-predominant Irritable Bowel Syndrome

Conditions
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Irritable Bowel Syndrome With Diarrhea, Irritable Bowel Syndrome

Intervention / Treatment
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* Dietary Supplement: Probiotic
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Probiotic<br>Arm receiving investigation product (probiotic) | Dietary Supplement: Probiotic<br>* Participants in this arm will receive a daily dose of 1x10^10 Colony Forming Unit (CFU) of a single strain probiotic (live bacteria), administered orally by 1 capsule a day, for 84 days<br>|
| Placebo Comparator: Placebo<br>Arm receiving placebo | Other: Placebo<br>* Participants in this arm will receive an equivalent placebo for 84 days.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in total irritable bowel syndrome symptom severity score (IBS-SSS) | Change in IBS-SSS totals score (max 500 points) from baseline to day 28, day 58 and day 84, where higher scores mean worse outcomes | Day 0, Day 28, Day 58 and Day 84 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of population achieving a normal stool consistency | Percentage of the population achieving normal stool consistency, defined as over 75% of total bowel movements classified as stool form type 3, 4, and 5 on Bristol Stool Form Scale (BSFS) (BSFS range: 1-7, lower scores mean constipation, higher scores mean diarrhea). Weekly percentage at baseline compared to weekly percentage at day 28, 58 and 84. | Day 0, Day 28, Day 58 and Day 84 | 
| Percentage of population without diarrhea | Percentage of the population where less than 25% of bowel movements are diarrhea, defined as stool form type 6 or 7 on the Bristol Stool Form Scale (BSFS) (BSFS range: 1-7, lower scores mean constipation, higher scores mean diarrhea). Weekly percentage calculated throughout study and compared to baseline weekly percentage. | Weekly | 
| Change in Irritable Bowel Syndrome Quality of Life (IBS-QOL) score | Change in quality of life, assessed by change in the IBS-QOL total score (max 100 points) between baseline and day 28, day 58 and day 84, where higher scores mean better quality of life | Day 0, Day 28, Day 58 and Day 84 | 
| Change in State-Trait Anxiety Inventory for Adults (STAI-AD) score | Mental health as assessed by change in STAI-AD S-anxiety subscale score (max: 80), between baseline and day 28, 58 and 84, where higher scores mean more severe anxiety symptoms | Day 0, Day 28, Day 58 and Day 84 | 
| Gut microbiome compositional changes | Change in gut microbiome composition, as assessed by shotgun sequencing of faecal samples, between baseline and study end (day 84) | Day 0, Day 84 | 
| Use of Rescue Medication | Comparison in total cumulative use of rescue medications between the two study arms at study end (day 84) | Day 0, Day 84 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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IBS, Probiotic, Irritable Bowel Syndrome, GI microbiome, Bifidobacterium