IBIS: Safety and Efficacy of a Probiotic Supplement in IBS-D

Sponsor

The Archer-Daniels-Midland Company (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT05754177

Collaborator

Vizera d.o.o. (Industry)

134

Enrollment

Arms

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Irritable Bowel Syndrome With Diarrhea Irritable Bowel Syndrome	Dietary Supplement: Probiotic Other: Placebo	N/A

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 adult IBS-D patients, 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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

134 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

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

Anticipated Study Start Date :

Mar 15, 2023

Anticipated Primary Completion Date :

Nov 15, 2023

Anticipated Study Completion Date :

Nov 15, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Probiotic Arm receiving investigation product (probiotic)	Dietary Supplement: Probiotic 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
Placebo Comparator: Placebo Arm receiving placebo	Other: Placebo Participants in this arm will receive an equivalent placebo for 84 days.

Arm

Intervention/Treatment

Experimental: Probiotic

Arm receiving investigation product (probiotic)

Dietary Supplement: Probiotic

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

Placebo Comparator: Placebo

Arm receiving placebo

Other: Placebo

Participants in this arm will receive an equivalent placebo for 84 days.

Outcome Measures

Primary Outcome Measures

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 Outcome Measures

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.
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)

Other Outcome Measures

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
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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts 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:

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.