Evaluating the Safety and Efficacy of the Probiotic Bifidobacterium Longum ES1 and the Post Biotic Heat-treated Bifidobacterium Longum ES1 (HT-ES1) on IBS Symptom Severity in Patients With Diarrhoea Predominant Irritable Bowel Syndrome

Study Overview
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Brief Summary
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Randomized controlled clinical study has been proposed to evaluate the safety and efficacy of ES1 probiotic strain and heat-treated ES1 postbiotic strain in individuals suffering from IBS-D.

Official Title
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Evaluating the Safety and Efficacy of the Probiotic Bifidobacterium Longum ES1 and the Post Biotic Heat-treated Bifidobacterium Longum ES1 (HT-ES1) on IBS Symptom Severity in Patients With Diarrhoea Predominant Irritable Bowel Syndrome

Conditions
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Irritable Bowel Syndrome With Diarrhea

Intervention / Treatment
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* Other: ES 1
* Other: HT ES1
* 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 movement 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 Lateral Flow Test Device. Participants who can comply and perform the procedures as per the protocol (consumption of study medications, biological sample collection procedures, and study visit schedule). Female participants who are willing to use acceptable contraceptives during the study duration. 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 diagnosed with anxiety as assessed by STAI-AD S- anxiety subscale score ≥ 40. Gluten and/or lactose intolerant individuals. Abnormal Thyroid Stimulating Hormone (TSH) value which is (< 0.4 to > 4.2 mIU/L). Participants with uncontrolled type II diabetes mellitus defined as random blood glucose (RBG) > 199 mg/dL or fasting blood glucose (FBG) >125 mg/dL. 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, synbiotic, proton pump inhibitors, acid sequestrants (cholestyramine, Bile colestipol), 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 before the screening day. Participants with a history of bariatric surgery or surgical resection of the stomach, small intestine, or large intestine. 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 malignant tumours. Participation in other clinical trials in the last 90 days prior to screening 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, tumour, and other gastrointestinal diseases.

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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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: A randomised, double-blind, placebo-controlled, parallel-group multicentre study
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: ES 1<br>Two capsules orally once daily after breakfast for 84 days | Other: ES 1<br>* Two capsules orally once daily after breakfast for 84 days<br>|
| Active Comparator: HT ES1<br>Two capsules orally once daily after breakfast for 84 days | Other: HT ES1<br>* Two capsules orally once daily after breakfast for 84 days<br>|
| Placebo Comparator: Placebo<br>Two capsules orally once daily after breakfast for 84 days | Other: Placebo<br>* Two capsules orally once daily after breakfast for 84 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Irritable Bowel Syndrome-Symptom Severity Scale | To determine the efficacy of investigational products on the participants global assessment of gastrointestinal symptoms, as assessed by change in Irritable Bowel Syndrome-Symptom Severity Scale total score at the end of study from baseline compared to placebo. Each of these 5 items is scored on a visual analogue scale from 0 to 100. Therefore, the total score on the ranges from 0 to 500. Participants are asked to respond to each question on a 100-point visual analogue scale. The higher the scores, the more will be the severity of symptoms. Participants, if required, can be categorized as having mild (75-175), moderate (175-300), Higher the score is the worst outcome and lower the score is the betterment. | day 0, 28, 56, and 84 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Bristol Stool Form Scale | At the end of days 28, 56, and 84, the percentage of participants transitioning to normal stool consistency (as demonstrated by weekly BSFS score reported as 3, 4, or 5) compared to baseline scores will be identified to evaluate the efficacy of IP in comparison to placebo. | day 0, 28, 56, and 84 | 
| Irritable Bowel Syndrome-Quality of Life | Quality of life as assessed by change in Irritable Bowel Syndrome-Quality of Life. It is a 34-item questionnaire with each item rated on a 5-point scale (34-170), with increasing scores indicating the deteriorating quality of life (Appendix-III). However, to facilitate comparisons among various measures on a standardized scale, the summed scores will be transformed to a 0 - 100 scale ranging from 0 (poor quality of life) to 100 (maximum quality of life). | day 0, 28, 56, and 84 | 
| Abdominal Pain Severity-Numeric Rating Scale score. | Abdominal pain severity as assessed by change in Abdominal Pain Severity-Numeric Rating Scale (APS-NRS) score. score ratings include 0 - None, 1 to 3 - Mild, 4 to 6 - Moderate, 7 to 9 - Severe, and 10 = very severe.4 | day 0, 28, 56, and 84 | 
| State-Trait Anxiety Inventory-Adults score. | Mental health as assessed by change in State-Trait Anxiety Inventory-Adults (STAI-AD) score. The State-Trait Anxiety Inventory has 40 items, 20 allocated to each S-Anxiety and T-Anxiety sub-scales . The range of scores for each subtest is 20-80, the higher score indicating greater anxiety. A cut point of 39-40 has been suggested to detect clinically significant symptoms for the S-Anxiety scale | day 0, 28, 56, and 84 | 
| Vitals - blood pressure | To evaluate the safety of IP consumption . Normal BP ranging Systolic120 - 129 mmHg and or diastolic 80 - 84 mm Hg | day 0, 28, 56, and 84 | 
| Gut microbiome as assessed by 16S rRNA sequencing of faecal samples. |  | day 0 and 84 | 
| Vitals - Pulse Rate | Normal Pulse rate 60 - 100 bpm | day 0, 28, 56, and 84 |