A study to assess effects of pasteurized Akkermansia muciniphila (Investigational Product) vs. placebo in participants with moderate to severe IBS-D.
Scientific Title of Study
A randomized, double blind, placebo controlled, parallel group clinical study to assess effects of pasteurized Akkermansia muciniphila vs. placebo in participants with moderate to severe diarrhea-predominant irritable bowel syndrome (PAM – DIGEST)
Trial Acronym
NIL
Secondary IDs if Any
Secondary ID
Identifier
TAC/231001/AKM/IBS, Version no. 1.0, Date: Feb 26, 2024
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Dr Shalini Srivastava
Designation
Director - Clinical Development and Strategy
Affiliation
Vedic Lifesciences Pvt. Ltd.
Address
B-118, Morya House, Off. New Link Road, Andheri (West), Mumbai, Maharashtra, India.
Mumbai MAHARASHTRA 400053 India
Phone
9920789140
Fax
Email
shalini.s@vediclifesciences.com
Details of Contact Person Scientific Query
Name
Dr Shalini Srivastava
Designation
Director - Clinical Development and Strategy
Affiliation
Vedic Lifesciences Pvt. Ltd.
Address
B-118, Morya House, Off. New Link Road, Andheri (West), Mumbai, Maharashtra, India.
Mumbai MAHARASHTRA 400053 India
Phone
9920789140
Fax
Email
shalini.s@vediclifesciences.com
Details of Contact Person Public Query
Name
Dr Sonal Raote
Designation
Manager - Clinical Operations
Affiliation
Vedic Lifesciences Pvt. Ltd.
Address
B-118, Morya House, Off. New Link Road, Andheri (West), Mumbai, Maharashtra, India.
Mumbai MAHARASHTRA 400053 India
Phone
7738373850
Fax
Email
sonal.raote@vediclifesciences.com
Source of Monetary or Material Support
Vedic Lifesciences Pvt. Ltd, B-118, Morya House, Off New Link Road, Andheri West, Mumbai - 400053
Institutional Ethics Committee GCS Medical College, Hospital and Research Center
Approved
Leelavati Institutional Ethics committee
Approved
Muktai Institutional Ethics Committee
Approved
Royal Pune Independent Ethics Committee
Approved
Royal Pune Independent Ethics Committee
Approved
Royal Pune Independent Ethics Committee
Approved
Royal Pune Independent Ethics Committee
Approved
Samvedna Hospital Ethics Committee
Approved
Regulatory Clearance Status from DCGI
Status
Not Applicable
Health Condition / Problems Studied
Health Type
Condition
Patients
(1) ICD-10 Condition: K580||Irritable bowel syndrome with diarrhea,
Intervention / Comparator Agent
Type
Name
Details
Intervention
Pasteurized Akkermansia muciniphila (pAKK)
1 capsule a day, 15 minutes before breakfast with a glass of water for 12 weeks
Comparator Agent
Placebo
1 capsule a day, 15 minutes before breakfast with a glass of water for 12 weeks.
Inclusion Criteria
Age From
18.00 Year(s)
Age To
55.00 Year(s)
Gender
Both
Details
1. Men and women from 18 to 55 years old.
2. Individuals diagnosed for IBS within the last two years, and meets Rome-IV criteria for IBS: recurrent abdominal pain on average ≥1 day/week in ≥3 months prior to study (with symptom onset ≥6 months prior to study), associated with ≥2 of the following criteria:
a. Related to defecation
b. Associated with a change in frequency of stool
c. Associated with a change in form (appearance) of stool.
3. Has IBS-D, i.e., more than one-fourth (25%) of bowel movements with Bristol stool types 6 or 7 and less than one-fourth (25%) of bowel movements with Bristol stool types 1 or 2); in other words, put practically and as per FDA: at least 2 days per week with at least one stool that has a consistency of Type 6 or Type 7 BSS.
4. Has an IBS-SSS of at least 175 points at screening.
5. Individuals either with abdominal pain or discomfort (≥ 6 to ≤ 10 on an 11-point scale).
6. Has had no prior line of conventional intervention for IBS or dietary change in the last 4 weeks before screening (e.g., low FODMAP, soluble fibers, antispasmodics, laxatives, obstipants, serotonin agonist/antagonist) i.e., recently diagnosed individuals.
7. Individuals’ agreement to comply with study procedures, in particular:
a. to take IP as recommended,
b. to avoid the use of other products which may influence the gastrointestinal (GI) complaints, mental symptoms or commensal flora during the study as defined in Section 6.8 Prior and Concomitant Therapy,
c. to keep the habitual dietary habits, level of physical activity as well as the level of caffeine or nicotine (if any),
d. to complete the individual’s diary and study questionnaires.
8. Women of childbearing potential:
a. commitment to use contraception methods,
b. Negative pregnancy testing (beta human chorionic gonadotropin test in urine).
9. Readiness not to participate in another clinical study during this study.
10. Participation is based upon written informed consent by the individual following written and oral information by the investigator regarding nature, purpose, consequences and possible risks of the clinical study.
ExclusionCriteria
Details
1. Known allergy or hypersensitivity to the components of the investigational product.
2. Smokers
3. Lactose or fructose intolerance
4. Individuals with uncontrolled hypertension as assessed by systolic blood pressure ≥ 160 mmHg and diastolic blood pressure ≥ 100mmHg.
5. History of diverticulitis, intestinal obstruction, stricture, toxic megacolon, GI (gastro-intestinal) perforation, fecal impaction, gastric banding, bariatric surgery, adhesions, ischemic colitis, or impaired intestinal circulation (e.g., aorto-iliac disease) or recent unexplained GI bleeding within 3 months prior to screening.
6. History of malignancy within 3 years before screening (except squamous and basal cell carcinomas and cervical carcinoma in situ).
7. History and/or presence of acute or chronic significant GI disease or digestion/absorption disorders (e.g., inflammatory bowel disease, coeliac disease, Clostridium difficile colitis, pancreatitis, disorders in digestive tract motility, gluten enteropathy, etc.)
8. Major gastric, hepatic, biliary, pancreas or intestinal surgery within the last 6 months prior to screening or planned during the study (appendectomy, hemorrhoidectomy, or polypectomy allowed as long as occurred more than 3 months prior to study screening; uncomplicated laparoscopic or open cholecystectomy is allowed if no history of post-operative biliary tract pain and surgery occurred more than 3 months prior to screening).
9. Clinically significant findings in colonoscopy within the 3 years prior to study.
10. Family history among first degree relatives of colorectal cancer or inflammatory bowel disease.
11. Individuals diagnosed with psychiatric disease (e.g., bipolar disorder, Schizophrenia) with or without medication in the last three years.
12. Individuals currently on medication for anxiety and/or depression.
13. Individual has a history and/or presence of other clinically significant condition/disorder, which per investigator’s judgement could interfere with the results of the study or the safety of the participants, e.g.:
a. thyroid gland disorder
b. hypertension
c. diabetes mellitus
d. eating disorder
e. immunodeficiency
f. relevant gynecological or urological disorder
g. any other relevant serious organ or systemic diseases ( e.g., cardiovascular, respiratory, liver, renal, neurological disease, etc.)
14. Regular medication and/or supplementation within the last month prior to and planned during the study:
a. antibiotics, probiotics, prebiotics within 4 weeks before enrollment for screening.
b. medication for IBS complaints, e.g., bile acid binders (cholestyramine), rifaximin, alosetron, lubiprostone, eluxadoline and linaclotide
c. which could influence gastrointestinal functions (e.g., laxatives, opioids, systemic corticosteroids, anti-cholinergics, anti-diarrheals, proton pump inhibitors, H2-blockers, etc.) as per investigator judgement. Exception: ad hoc use of Macrolits.
15. Regular use of psychopharmaca (e.g., hypnotics / sedative drugs, anxiolytics, antidepressants, neuroleptics, anticonvulsants) within 3 months prior to study or adaptogens (e.g., ginseng, Ashwagandha, satavari, St. John’s Wort) within 6 weeks prior to and during the study.
16. Introductions of a specific diet (e.g., low carb, vegan, high fibre, low FODMAP) within last 3 months prior to and during the study.
17. Women of child-bearing potential: pregnancy or nursing.
18. History of or current abuse of drugs, alcohol, tobacco/nicotine or medication.
19. Participation in another study during the last 30 days prior to and during the study.
Any other reason for exclusion as per investigator’s judgment, e.g., insufficient compliance with study procedures.
Method of Generating Random Sequence
Stratified block randomization
Method of Concealment
Sequentially numbered, sealed, opaque envelopes
Blinding/Masking
Participant, Investigator and Outcome Assessor Blinded
Primary Outcome
Outcome
TimePoints
To assess the impact of pasteurized Akkermansia muciniphila relative to placebo on percentage responders in terms of improvement of the IBS-Symptom Severity Scores (SSS) in participants with moderate to severe diarrhea-predominant irritable bowel syndrome. [A responder is defined as a participant who has a decrease in IBS-SSS of at least 50 points (minimal clinically important difference or MCID)].
Baseline (Day 0), and Week 12 (Day 84)
Secondary Outcome
Outcome
TimePoints
To assess the impact of pasteurized Akkermansia muciniphila relative to placebo on the proportion of percentage of participants who are responders in terms of improvement of the IBS-SSS from baseline at week 8.
To assess the impact of pasteurized Akkermansia muciniphila relative to placebo on The proportion of percentage of participants who are responders in terms of improvement of the GAD -7 score.
To assess the impact of pasteurized Akkermansia muciniphila relative to placebo on the proportion of percentage of participants who are responders in terms of improvement of the PHQ-9 score
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
Brief Summary
The present study is a randomized, double-blind, placebo-controlled, parallel group clinical study. Up to around 475 individuals will be screened, and considering a screening failure rate of 20%, approximately 380 will be randomized in a ratio of 1:1 to receive either pasteurized A. muciniphila (pAKK) or matching placebo after a post-screening 14-day placebo run-in phase. Each group will have at least 152 completed participants (total 304 completers) after accounting for a dropout/withdrawal rate of 20%. The intervention duration for all the study participants is 12 weeks (intervention phase). Subsequently, the participants will be invited to return to site for an end of study assessment after 14 days of no intervention (post-intervention phase).