Study to Evaluate the Effect of Pasteurized Akkermansia Muciniphila (pAkk) on Complaints Related to IBS

Study Overview
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Brief Summary
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Double-blind, randomised, placebo-controlled study to evaluate the benefit of pasteurized Akkermansia muciniphila in reducing complaints related to irritable bowel syndrome. Further objectives are to evaluate the beneficial potential of pAkk on any anxiety and depression complaints, as well as its safety and tolerability.

Detailed Description
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Irritable bowel syndrome (IBS) is one of the most common disorders of gut-brain interaction, globally affecting about 10% of the population. Typical predominant traits are abdominal pain and abnormal bowel habits. The use of probiotics in IBS has been continuously assessed; in recent systematic reviews and meta-analyses, single or combined probiotic strains were indicated to have beneficial effects and good tolerability in the affected population. pAkk has recently been assessed as a safe novel food ingredient. Beneficial effects and very good tolerability of pAkk have been reported in individuals with metabolic disorders. The objective of the present clinical study - a double-blind, randomised, placebo-controlled, parallel group design, explorative pilot 12-week nutritional study, is to assess the potential of pAkk in IBS management. The main study objective is then to evaluate the benefit of pAkk in reducing complaints related to irritable bowel syndrome. Further objectives are to evaluate the beneficial potential of pAkk on any anxiety and depression complaints, as well as its safety and tolerability. In total, 90 participants will be enrolled and will attend 4 study visits: one on site and 3 televisits.

Official Title
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Study to Evaluate the Effect of Pasteurized Akkermansia Muciniphila (pAkk) on Complaints Related to Irritable Bowel Syndrome

Conditions
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Irritable Bowel Syndrome

Intervention / Treatment
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* Dietary Supplement: pasteurized A. muciniphila
* Dietary Supplement: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men and women from 18 to 70 years old Meeting 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: Related to defecation Associated with a change in frequency of stool Associated with a change in form (appearance) of stool Consistent and stable body weight in the last 3 months prior to study (less than 5% self-reported change) Having access to a smartphone or a computer with an internet access, either allowing a video call, and familiar with the use thereof (checked during the visit) Subject's agreement to comply with study procedures, in particular: to take IP as recommended to avoid the use of other products which may influence the GI complaints during the study to keep the habitual dietary habits, type and level of physical activity (including any specific exercise such as e.g. yoga) as well as the level of caffeine or nicotine (if any) to complete the subject diary and study questionnaires Women of childbearing potential: commitment to use contraception methods negative pregnancy testing (beta human chorionic gonadotropin test in urine) Readiness not to participate in another clinical study during this study Exclusion Criteria: Self-reported known allergy or hypersensitivity to any of the components of the investigational product Self-reported nocturnal GI complaints Women of childbearing potential: self-reported GI complaints mainly related to menstruation Self-reported lactose or fructose intolerance Self-reported acute or chronic significant GI disease or digestion/absorption disorders (e.g. inflammatory bowel disease, coeliac disease, pancreatitis, disorders in digestive tract motility etc.) Self-reported local anorectal problems (e.g. anal fissure, bleeding haemorrhoids) Self-reported clinically significant findings in colonoscopy within the 2 years prior to study Family history (immediate family) of colorectal cancer or inflammatory bowel disease; anxiety or depression requiring medication Acute or chronic psychiatric disease (e.g. depression, anxiety, bipolar disorder) requiring medication 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 subject, e.g.: unstable thyroid gland disorder unstable hypertension unstable diabetes mellitus eating disorder immunodeficiency relevant gynecological or urological disorder any other relevant serious organ or systemic diseases (e.g. cardiovascular, liver, renal disease etc.) Significant GI surgery within the last 6 months prior to or planned during the study Regular medication and/or supplementation within the last month prior to and during the study: antibiotics, probiotics, metformin for management of IBS complaints, such as bile acid binders (e.g. cholestyramine), rifaximin, alosetron, lubiprostone, eluxadoline, linaclotide, peppermint oil that could influence gastrointestinal functions (e.g. laxatives, opioids, systemic corticosteroids, anticho-linergics, anti-diarrheals etc.) as per investigator judgement Regular use of psychotropic drugs (e.g. hypnotics / sedative drugs, anxiolytics, antidepressants, neuroleptics, anticonvulsants) within 3 months prior to study or adaptogens (e.g. ginseng, St. John's Wort) within 6 weeks prior to and during the study Introductions of a specific diet (e.g. low carb, vegan, high-fibre, low FODMAP within last 3 months prior to and during the study Women of child-bearing potential: pregnancy or nursing History of or current abuse of drugs, alcohol or medication 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Parallel Assignment randomized, double-blind, placebo-controlled, parallel group, single center trial
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental group receiving pasteurized Akkermansia muciniphila<br>pasteurized Akkermansia muciniphila - daily oral dose | Dietary Supplement: pasteurized A. muciniphila<br>* pasteurized A. muciniphila - oral daily dose<br>|
| Placebo Comparator: Control group<br>Control group receiving placebo, identical to verum regarding the form, size, taste, color and intake. | Dietary Supplement: placebo<br>* Placebo = identical to verum regarding the form, size, taste, color and intake<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Irritable Bowel Severity Scoring System / IBS-SSS | Changes at each timepoint of assessment in comparison to baseline. IBS-SSS is between 0 and 500, with a higher score meaning more severe symptoms. | From baseline to day 14, day 42 and day 84 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 3-day diary data on stool consistency (Bristol Stool Form Scale / BSFS) | Changes at each timepoint of assessment in comparison to baseline. The Bristol Stool Form Scale is a 7 score visual scale to measure stool consistency. (1) Separate hard lumps like nuts (difficult to pass); (2) Sausage-shaped but lumpy; (3) Like a sausage but with cracks on its surface; (4) Like a sausage or snake, smooth and soft; (5) Soft blobs with clear-cut edges (passed easily); (6) Fluffy pieces with ragged edges, a mushy stool; (7) Watery, no solid pieces, entirely liquid. | From baseline to day 14, day 42 and day 84 | 
| Hospital Anxiety and Depression Scale / HADS | Changes at each timepoint of assessment in comparison to baseline. The HADS is a fourteen item scale. Seven of the items relate to anxiety and seven relate to depression. The anxiety and depression subscales each range from 0 to 21, with higher scores indicating higher anxiety/depression complains. Patients were defined as having anxiety or depression or both if the score was 8 or more in the corresponding subscale. | From baseline to day 14, day 42 and day 84 | 
| SF-12: 12-item Short Form survey | Changes at each timepoint of assessment in comparison to baseline. The SF-12 consists of 12 items questioned weighted and summed to provide physical and mental health scores (PCS and MCS). The two composite scores are computed using the scores on twelve questions that range from 0 to 100, with higher score indicating better health. | From baseline to day 42 and day 84 | 
| Global evaluation of tolerability by subject and investigator | Changes in comparison to baseline. 8 weeks after the baseline, the subjects and the investigator will rate the tolerability of the IP by means of a global scaled evaluation with very good, good, moderate and poor | From baseline to day 84 | 
| Irritable Bowel Syndrome-Global Improvement Scale / IBS-GIS | Changes at each timepoint of assessment in comparison to baseline. The IBS-GIS is a single item assessment of overall IBS symptoms. It poses the question to study participants How would you rate your IBS signs or symptoms over the past 7 days: Subjects respond on a scale of 1-7 where: 1 = Significantly relieved, 2 = Moderately relieved, 3 = Slightly relieved, 4 = Unchanged, 5 = Slightly worse, 6 = Moderately worse, 7 = Significantly worse. | From baseline to day 14, day 42 and day 84 | 
| 3-day diary data on stool frequency | Changes at each timepoint of assessment in comparison to baseline | From baseline to day 84 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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IBS