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

Not Applicable

Completed

• Conditions: Irritable Bowel Syndrome With Diarrhea
• Interventions: Other: Placebo; Other: ES 1; Other: HT ES1

• Registration Number: NCT05339243
• Lead Sponsor: Vedic Lifesciences Pvt. Ltd.

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2022-04-13
• Study First Submitted QC: 2022-04-13
• Study Start: 2022-04-21
• Study First Posted: 2022-04-21
• Primary Completion: 2023-01-13
• Study Completion: 2023-01-13
• Status Verified: 2023-09
• Last Update Submitted: 2023-09-07
• Last Update Posted: 2023-09-08

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 200

Inclusion Criteria

1. Males and females aged ≥18 to ≤ 65 years.

2. 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).

3. Participants with an IBS-SSS score ≥ 175.

4. Participants who test negative for COVID-19 by Rapid Antigen Lateral Flow Test Device.

5. 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.

6. Participants who are literate enough to understand the purpose of the study and their rights.

7. Participants who are able to give written informed consent and are willing to participate in the study.

Exclusion Criteria

1. Participants diagnosed with anxiety as assessed by STAI-AD S- anxiety subscale score ≥ 40.
2. Gluten and/or lactose intolerant individuals.
3. Abnormal Thyroid Stimulating Hormone (TSH) value which is (< 0.4 to > 4.2 mIU/L).
4. Participants with uncontrolled type II diabetes mellitus defined as random blood glucose (RBG) > 199 mg/dL or fasting blood glucose (FBG) >125 mg/dL.
5. Participants with a body mass index (BMI) ≥ 30 kg/m2.
6. Presence of uncontrolled hypertension defined as systolic blood pressure (SBP) ≥ 140 mm Hg and/or diastolic blood pressure (DBP) ≥ 90 mm Hg.
7. 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.
8. 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.
9. Participants with a history of bariatric surgery or surgical resection of the stomach, small intestine, or large intestine.
10. 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.
11. Participants with a history of or complications from malignant tumours.
12. Participation in other clinical trials in the last 90 days prior to screening
13. Active smokers or using any form of smokeless tobacco.
14. Participants with substance abuse problems (within two years) defined as:
15. Use of recreational drugs (such as cocaine, methamphetamine, marijuana, etc.)/Nicotine dependence.
16. 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.
17. 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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Two capsules orally once daily after breakfast for 84 days
ES 1	ES 1	Two capsules orally once daily after breakfast for 84 days
HT ES1	HT ES1	Two capsules orally once daily after breakfast for 84 days

Primary Outcome Measures

Name	Time	Method
Irritable Bowel Syndrome-Symptom Severity Scale	day 0, 28, 56, and 84	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.

Secondary Outcome Measures

Name	Time	Method
Vitals - Pulse Rate	day 0, 28, 56, and 84	Normal Pulse rate 60 - 100 bpm
Gut microbiome as assessed by 16S rRNA sequencing of faecal samples.	day 0 and 84
Bristol Stool Form Scale	day 0, 28, 56, and 84	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.
Irritable Bowel Syndrome-Quality of Life	day 0, 28, 56, and 84	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).
Abdominal Pain Severity-Numeric Rating Scale score.	day 0, 28, 56, and 84	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
State-Trait Anxiety Inventory-Adults score.	day 0, 28, 56, and 84	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
Vitals - blood pressure	day 0, 28, 56, and 84	To evaluate the safety of IP consumption .; Normal BP ranging Systolic120 - 129 mmHg and or diastolic 80 - 84 mm Hg

Trial Locations

Locations (8)

Shantaee Nursing Home; 🇮🇳 Mumbai, Maharashtra, India

Stress test clinic; 🇮🇳 Mumbai, Maharashtra, India

Jaipur National University Institute for Medical Science & Research Centre; 🇮🇳 Jaipur, Rajasthan, India

Dr. Sudhir Maharshi clinic; 🇮🇳 Jaipur, Rajasthan, India

Apex Gastro Clinic and Hospital; 🇮🇳 Ahmedabad, Gujarat, India

Aman Hospital and research centre; 🇮🇳 Vadodara, Gujarat, India

Dr. Sanjeev Khanna clinic; 🇮🇳 Mumbai, Maharashtra, India

Gastroplus, Digestive disease centre; 🇮🇳 Ahmedabad, Gujarat, India