A study to assess effects of pasteurized Akkermansia muciniphila (Investigational Product) vs. placebo in participants with moderate to severe IBS-D.

Phase 4

• Conditions: Health Condition 1: K580- Irritable bowel syndrome with diarrhea

• Registration Number: CTRI/2024/05/067212
• Lead Sponsor: The Akkermansia Company

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Last Update Posted: 19 August 2024

Recruitment & Eligibility

• Status: Open to Recruitment
• Sex: Not specified
• Target Recruitment: 0

Inclusion Criteria

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.

Exclusion Criteria

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 du

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
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)].Timepoint: Baseline (Day 0), and Week 12 (Day 84)