Irritable Bowel Syndrome, Irritable Bowel Syndrome With Diarrhea
Conditions
Keywords
IBS, Probiotic, Irritable Bowel Syndrome, GI microbiome, Bifidobacterium
Brief summary
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
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.
Interventions
DIETARY_SUPPLEMENTProbiotic
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
OTHERPlacebo
Participants in this arm will receive an equivalent placebo for 84 days.
Sponsors
Vizera d.o.o.
The Archer-Daniels-Midland Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in total irritable bowel syndrome symptom severity score (IBS-SSS) | Day 0, Day 28, Day 58 and Day 84 | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Irritable Bowel Syndrome Quality of Life (IBS-QOL) score | Day 0, Day 28, Day 58 and Day 84 | 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 |
| Change in State-Trait Anxiety Inventory for Adults (STAI-AD) score | Day 0, Day 28, Day 58 and Day 84 | 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 |
| Gut microbiome compositional changes | Day 0, Day 84 | Change in gut microbiome composition, as assessed by shotgun sequencing of faecal samples, between baseline and study end (day 84) |
| Use of Rescue Medication | Day 0, Day 84 | Comparison in total cumulative use of rescue medications between the two study arms at study end (day 84) |
| Percentage of population achieving a normal stool consistency | Day 0, Day 28, Day 58 and Day 84 | 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. |
| Percentage of population without diarrhea | Weekly | 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Proton Pump Inhibitor Use | Day 0, Day 84 | Subpopulation analysis: participants taking proton pump inhibitors (PPIs) and participants not taking PPIs compared to placebo at study end |
| Adverse Events | Day 0, Day 84 | Comparison in the total number of adverse events/serious adverse events occurred during the study, from baseline to study end (day 84), between the two study arms |
| Stool Biochemistry | Day 0, Day 84 | Change in stool faecal biochemistry between baseline and study end (day 84) between the two study arms |
Countries
Slovenia
Outcome results
None listed