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

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.

Study Overview

• Status: Completed
• Conditions: Irritable Bowel Syndrome With Diarrhea
• Intervention / Treatment: Other: ES 1; Other: HT ES1; Other: Placebo

• Study Type: Interventional
• Enrollment (Actual): 200
• Phase: Not Applicable

Contacts and Locations

Study Locations

• India
  • Gujarat
    • Ahmedabad, Gujarat, India, 380013
      • Apex Gastro Clinic and Hospital
    • Ahmedabad, Gujarat, India, 380054
      • Gastroplus, Digestive disease centre
    • Vadodara, Gujarat, India, 390021
      • Aman Hospital and Research Centre
  • Maharashtra
    • Mumbai, Maharashtra, India, 400059
      • Stress Test Clinic
    • Mumbai, Maharashtra, India, -400067
      • Shantaee Nursing Home
    • Mumbai, Maharashtra, India, 400059
      • Dr. Sanjeev Khanna clinic
  • Rajasthan
    • Jaipur, Rajasthan, India, -302017
      • Jaipur National University Institute for Medical Science & Research Centre
    • Jaipur, Rajasthan, India, 302001
      • Dr. Sudhir Maharshi clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: ES 1; Two capsules orally once daily after breakfast for 84 days	Other: ES 1; Two capsules orally once daily after breakfast for 84 days
Active Comparator: HT ES1; Two capsules orally once daily after breakfast for 84 days	Other: HT ES1; Two capsules orally once daily after breakfast for 84 days
Placebo Comparator: Placebo; Two capsules orally once daily after breakfast for 84 days	Other: Placebo; Two capsules orally once daily after breakfast for 84 days

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Vedic Lifesciences Pvt. Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): April 21, 2022
• Primary Completion (Actual): January 13, 2023
• Study Completion (Actual): January 13, 2023

Study Registration Dates

• First Submitted: April 13, 2022
• First Submitted That Met QC Criteria: April 13, 2022
• First Posted (Actual): April 21, 2022

Study Record Updates

• Last Update Posted (Actual): September 8, 2023
• Last Update Submitted That Met QC Criteria: September 7, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Disease; Signs and Symptoms, Digestive; Gastrointestinal Diseases; Colonic Diseases, Functional; Colonic Diseases; Intestinal Diseases; Syndrome; Irritable Bowel Syndrome; Diarrhea
• Other Study ID Numbers: ADM/211001/BLE/IBS

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No