The Efficacy of Pasteurised Akkermansia Muciniphila in Healthy Medical Workers

Healthy Clinical Trial

— MENTAkHEALTH  

Official title:

The Effects of the Anti-inflammatory Microbe - Pasteurized Akkermansia Muciniphila (PAM) on Symptoms of Somatic and Mental Stress in Healthcare Professionals

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05738746
• Other study ID #: 101095540
• Status: Recruiting
• Phase: N/A
• Start date: October 24, 2023
• Est. completion date: February 28, 2026

Study information

• Verified date: November 2023
• Source: Pomeranian Medical University Szczecin
• Contact: Jerzy Samochowiec, Prof.
• Phone: +48914800886
• Email: jerzy.samochowiec[@]pum.edu.pl
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Gut microbiota alterations secondary to chronic stress might serve as a triggering factor towards manifestation of somatic and mental symptoms. The administration of pasteurised A. muciniphila MucT has the capability of supporting microbiota and improving the gut barrier integrity, which might lead to decrease of inflammation and the negative health consequences of stress in healthy participants.

Description:

The Gut-brain-microbiota axis (GBMA) is a bi-directional pathway, both neuronal and biochemical, between the intestine and the Central Nervous System (CNS). The gut microbiota plays a central role in gut-brain communication. The composition of intestinal microbiota and its functions play an important role in the pathogenesis of disorders of gut-brain interaction - both within the digestive tract and in the brain.

Modulation of gut microbiota with the aid of probiotics, antibiotics, or germ-free feeding protocols significantly altered stressful event-induced behavioral outcomes in rodents. Moreover, the intake of various probiotics significantly improved stress-induced anxiety and depressive-like behaviors in mice. In humans, probiotics were also documented to display some beneficial effects on mental health, including alteration of emotional bias in healthy individuals, and alleviating stress and anxiety among stressed adults.

Psychobiotics are imposed with certain limitations related to their standardization and end-shelf-life product stability. Therefore, the use of postbiotics, which contain bacterial metabolites or other bacteria derived fragments are viewed as novel solutions and alternatives to use of standard probiotics. One of novel postbiotics of interest among scientists and clinicians is pasteurized Akkermansia muciniphila MucT (PAM).

Animal studies indicate that administration of Akkermansia muciniphila can ameliorate metabolic syndrome, obesity, diabetes, and inflammatory bowel disease in animals and has psychobiotic potential. Similar to live A. muciniphila, PAM could ameliorate several diseases as well. The mechanism of action of PAM - improving gut barrier integrity - suggests the potential use to reduce the negative effects of stress. Human studies shown that PAM is safety, what was confirmed in the Scientific Opinion of EFSA. Recently A. muciniphila was approved as the Novel Food.

A proof of concept study will be conducted to verify the hypothesis that PAM reduces the psychological and somatic effects of stress.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 200
• Est. completion date: February 28, 2026
• Est. primary completion date: August 31, 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

• Working in a high stress hospital department, like: emergency, trauma, intensive care, surgery, internal diseases;

• Written informed consent to participate in this study before any study-mandated procedure;

• Body mass index (BMI) =18.5 kg/m2 and = 35 kg/m2;

• A willingness and motivation to follow the study protocol.

Exclusion Criteria:

• Diagnosis of autoimmune, neurological, immunocompromised, thyroid, inflammatory bowel diseases, irritable bowel syndrome, diabetes, cancer, and/or IgE-dependent allergy;

• Psychiatric comorbidities, including mental retardation, organic brain dysfunction, or addiction (except nicotine and caffeine), intake of antipsychotic and antidepressive drugs;

• Proton pump inhibitors usage;

• The use of antibiotics and/or probiotics 4 weeks prior to the study;

• Glucocorticosteroids and/or metformin treatment;

• Dietary supplementation (except for vitamin D) within the three months before screening;

• Specific restrictive (e.g. elimination, vegan, FODMAP, reduction) diet within the three months before screening;

• Significant changes in physical activity 4 weeks before the trial entry;

• Pregnancy or lactation;

• Significant GI surgery within the last 6 months prior to or planned during the study;

• Any other medication for management of IBS complaints like peppermint oil, bile acid binders;

• Lactose intolerance;

• 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.

Related Conditions & MeSH terms

• Dietary Supplement
• Healthy
• Stress

Intervention

Dietary Supplement:
• Pasteurized Akkermansia muciniphila
PAM supplementation; packaging will be given to the subjects every one month during follow-up visits, with the instructions to take one dose every morning on an empty stomach
• Placebo
PBO administration; packaging will be given to the subjects every one month during follow-up visits, with the instructions to take one dose every morning on an empty stomach

Locations

Country	Name	City	State
Poland	Center fo Medical Simulation	Szczecin	Zachodniopomorskie
Poland	Pomeranian Medical University in Szczecin	Szczecin	Zachodniopomorskie

Sponsors (6)

Lead Sponsor	Collaborator
Pomeranian Medical University Szczecin	Charite University, Berlin, Germany, Imperial College London, MAX DELBRUECK CENTRUM FUER MOLEKULARE MEDIZIN IN DER HELMHOLTZ-GEMEINSCHAFT (MDC) - MDC, SANPROBI SPOLKA Z OGRANICZONA ODPOWIEDZIALNOSCIA SPOLKA KOMANDYTOWA, THE AKKERMANSIA COMPANY

Country where clinical trial is conducted

Poland, 

References & Publications (4)

Cani PD, Depommier C, Derrien M, Everard A, de Vos WM. Akkermansia muciniphila: paradigm for next-generation beneficial microorganisms. Nat Rev Gastroenterol Hepatol. 2022 Oct;19(10):625-637. doi: 10.1038/s41575-022-00631-9. Epub 2022 May 31. Erratum In: Nat Rev Gastroenterol Hepatol. 2022 Jun 23;: — View Citation

Depommier C, Everard A, Druart C, Plovier H, Van Hul M, Vieira-Silva S, Falony G, Raes J, Maiter D, Delzenne NM, de Barsy M, Loumaye A, Hermans MP, Thissen JP, de Vos WM, Cani PD. Supplementation with Akkermansia muciniphila in overweight and obese human volunteers: a proof-of-concept exploratory study. Nat Med. 2019 Jul;25(7):1096-1103. doi: 10.1038/s41591-019-0495-2. Epub 2019 Jul 1. — View Citation

Druart C, Plovier H, Van Hul M, Brient A, Phipps KR, de Vos WM, Cani PD. Toxicological safety evaluation of pasteurized Akkermansia muciniphila. J Appl Toxicol. 2021 Feb;41(2):276-290. doi: 10.1002/jat.4044. Epub 2020 Jul 28. — View Citation

Schneeberger M, Everard A, Gomez-Valades AG, Matamoros S, Ramirez S, Delzenne NM, Gomis R, Claret M, Cani PD. Akkermansia muciniphila inversely correlates with the onset of inflammation, altered adipose tissue metabolism and metabolic disorders during obesity in mice. Sci Rep. 2015 Nov 13;5:16643. doi: 10.1038/srep16643. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Stress intensity	serum dehydroepiandrosterone sulfate (DHEAS) in blood	baseline
Primary	Stress intensity	serum dehydroepiandrosterone sulfate (DHEAS) in blood	1 month
Primary	Stress intensity	serum dehydroepiandrosterone sulfate (DHEAS) in blood	3 months
Primary	Cardiovascular marker of stressor intensity	blood pressure	baseline
Primary	Cardiovascular marker of stressor intensity	blood pressure	1 month
Primary	Cardiovascular marker of stressor intensity	blood pressure	3 months
Primary	Cardiovascular marker of stressor intensity	heart rate	baseline
Primary	Cardiovascular marker of stressor intensity	heart rate	1 month
Primary	Cardiovascular marker of stressor intensity	heart rate	3 months
Primary	Stress intensity	Perceived Stress Scale (PSS-10). Individual scores on the PSS can range from 0 to 40 with higher scores indicating higher perceived stress.	baseline
Primary	Stress intensity	Perceived Stress Scale (PSS-10). Individual scores on the PSS can range from 0 to 40 with higher scores indicating higher perceived stress.	1 month
Primary	Stress intensity	Perceived Stress Scale (PSS-10). Individual scores on the PSS can range from 0 to 40 with higher scores indicating higher perceived stress.	3 months
Primary	Psychosocial working conditions	Copenhagen Psychosocial Questionnaire (COPSOQ). The scales of the COPSOQ are formed by adding the points of the individual questions of the scales by giving equal weights to each question. In most cases the questions have five response options. In these cases the weights are: 0, 25, 50, 75, and 100. The scale value is calculated as the simple average	baseline
Primary	Psychosocial working conditions	Copenhagen Psychosocial Questionnaire (COPSOQ). The scales of the COPSOQ are formed by adding the points of the individual questions of the scales by giving equal weights to each question. In most cases the questions have five response options. In these cases the weights are: 0, 25, 50, 75, and 100. The scale value is calculated as the simple average	1 month
Primary	Psychosocial working conditions	Copenhagen Psychosocial Questionnaire (COPSOQ). The scales of the COPSOQ are formed by adding the points of the individual questions of the scales by giving equal weights to each question. In most cases the questions have five response options. In these cases the weights are: 0, 25, 50, 75, and 100. The scale value is calculated as the simple average	3 months
Primary	The recognition of the most common mental disorders	Primary Care Evaluation of Mental Disorders (PRIME-MD). The yes/no questionnaire serves as an initial screen for 5 general groups of mental disorders commonly found in the general population	baseline
Primary	The recognition of the most common mental disorders	Primary Care Evaluation of Mental Disorders (PRIME-MD). The yes/no questionnaire serves as an initial screen for 5 general groups of mental disorders commonly found in the general population	1 month
Primary	The recognition of the most common mental disorders	Primary Care Evaluation of Mental Disorders (PRIME-MD). The yes/no questionnaire serves as an initial screen for 5 general groups of mental disorders commonly found in the general population	3 months
Primary	Depression	Patient Health Questionnaire-9 (PHQ-9). Nine items, each of which is scored 0 to 3, providing a 0 to 27 severity score.This score can then be referred to the accompanying PHQ-9 Scoring Box to interpret the TOTAL score.	baseline
Primary	Depression	Patient Health Questionnaire-9 (PHQ-9). Nine items, each of which is scored 0 to 3, providing a 0 to 27 severity score.This score can then be referred to the accompanying PHQ-9 Scoring Box to interpret the TOTAL score.	1 month
Primary	Depression	Patient Health Questionnaire-9 (PHQ-9). Nine items, each of which is scored 0 to 3, providing a 0 to 27 severity score.This score can then be referred to the accompanying PHQ-9 Scoring Box to interpret the TOTAL score.	3 months
Primary	Depressive state	The Beck Depression Inventory (BDI). When the test is scored, a value of 0 to 3 is assigned for each answer and then the total score is compared to a key to determine the depression's severity. The standard cut-off scores were as follows: 0-18: indicates minimal depression 18-30: indicates mild depression 19-29: indicates moderate depression 30-63: indicates severe depression.	baseline
Primary	Depressive state	The Beck Depression Inventory (BDI). When the test is scored, a value of 0 to 3 is assigned for each answer and then the total score is compared to a key to determine the depression's severity. The standard cut-off scores were as follows: 0-18: indicates minimal depression 18-30: indicates mild depression 19-29: indicates moderate depression 30-63: indicates severe depression.	1 month
Primary	Depressive state	The Beck Depression Inventory (BDI). When the test is scored, a value of 0 to 3 is assigned for each answer and then the total score is compared to a key to determine the depression's severity. The standard cut-off scores were as follows: 0-18: indicates minimal depression 18-30: indicates mild depression 19-29: indicates moderate depression 30-63: indicates severe depression.	3 months
Primary	Anxiety and stress	Depression Anxiety Stress Scale 21 (DASS-21). This is a set of three self-report scales designed to measure the emotional states of depression, anxiety and stress. The rating scale is as follows: 0 - Did not apply to me at all; - Applied to me to some degree, or some of the time; - Applied to me to a considerable degree, or a good part of time; - Applied to me very much, or most of the time.; SUBSCALES: DASS_Anxiety = questions 2 + 4 + 7 + 9 + 15 + 19 + 20; DASS_Depression = questions 3 + 5 + 10 + 13 + 16 + 17 + 21; DASS_Stress = questions 1 + 6 + 8 + 11 + 12 + 14 +18	baseline
Primary	Anxiety and stress	Depression Anxiety Stress Scale 21 (DASS-21). This is a set of three self-report scales designed to measure the emotional states of depression, anxiety and stress. The rating scale is as follows: 0 - Did not apply to me at all; - Applied to me to some degree, or some of the time; - Applied to me to a considerable degree, or a good part of time; - Applied to me very much, or most of the time.; SUBSCALES: DASS_Anxiety = questions 2 + 4 + 7 + 9 + 15 + 19 + 20; DASS_Depression = questions 3 + 5 + 10 + 13 + 16 + 17 + 21; DASS_Stress = questions 1 + 6 + 8 + 11 + 12 + 14 +18	1 month
Primary	Anxiety and stress	Depression Anxiety Stress Scale 21 (DASS-21). This is a set of three self-report scales designed to measure the emotional states of depression, anxiety and stress. The rating scale is as follows: 0 - Did not apply to me at all; - Applied to me to some degree, or some of the time; - Applied to me to a considerable degree, or a good part of time; - Applied to me very much, or most of the time.; SUBSCALES: DASS_Anxiety = questions 2 + 4 + 7 + 9 + 15 + 19 + 20; DASS_Depression = questions 3 + 5 + 10 + 13 + 16 + 17 + 21; DASS_Stress = questions 1 + 6 + 8 + 11 + 12 + 14 +18	3 months
Primary	Occurrence of Irritable Bowel Syndrome	Rome IV criteria	baseline
Primary	Occurrence of Irritable Bowel Syndrome	Rome IV criteria	1 month
Primary	Occurrence of Irritable Bowel Syndrome	Rome IV criteria	3 months
Primary	Occurence and severity of gastrointestinal symptoms	Gastrointestinal Symptom Rating Scale (GSRS)	baseline
Primary	Occurence and severity of gastrointestinal symptoms	Gastrointestinal Symptom Rating Scale (GSRS)	1 month
Primary	Occurence and severity of gastrointestinal symptoms	Gastrointestinal Symptom Rating Scale (GSRS)	3 months
Secondary	Microbiota composition	next generation sequencing	baseline
Secondary	Microbiota composition	next generation sequencing	1 month
Secondary	Microbiota composition	next generation sequencing	3 months
Secondary	A. muciniphila count in stool	real-time quantitative PCR (qPCR)	baseline
Secondary	A. muciniphila count in stool	real-time quantitative PCR (qPCR)	1 month
Secondary	A. muciniphila count in stool	real-time quantitative PCR (qPCR)	3 months
Secondary	Total bacteria count in stool	real-time quantitative PCR (qPCR)	baseline
Secondary	Total bacteria count in stool	real-time quantitative PCR (qPCR)	1 month
Secondary	Total bacteria count in stool	real-time quantitative PCR (qPCR)	3 months
Secondary	Short chain fatty acids content in stool	quadrupole mass spectrometer and high performance liquid chromatograph	baseline
Secondary	Short chain fatty acids content in stool	quadrupole mass spectrometer and high performance liquid chromatograph	1 month
Secondary	Short chain fatty acids content in stool	quadrupole mass spectrometer and high performance liquid chromatograph	3 months
Secondary	Immune phenotypes of peripheral blood mononuclear cells (PBMCs)	single-cell genomics (scRNA-seq and scATAC-seq) analyses (in blood)	baseline
Secondary	Immune phenotypes of peripheral blood mononuclear cells (PBMCs)	single-cell genomics (scRNA-seq and scATAC-seq) analyses (in blood)	1 month
Secondary	Immune phenotypes of peripheral blood mononuclear cells (PBMCs)	single-cell genomics (scRNA-seq and scATAC-seq) analyses (in blood)	3 months
Secondary	Inflammatory mediators concentrations in blood	high-throughput protein biomarker analysis with the advent of Proximity Extension Assay	baseline
Secondary	Inflammatory mediators concentrations in blood	high-throughput protein biomarker analysis with the advent of Proximity Extension Assay	1 month
Secondary	Inflammatory mediators concentrations in blood	high-throughput protein biomarker analysis with the advent of Proximity Extension Assay	3 months
Secondary	Zonulin concentration in stool	enzyme-linked immunosorbent assay (ELISA)	baseline
Secondary	Zonulin concentration in stool	enzyme-linked immunosorbent assay (ELISA)	1 month
Secondary	Zonulin concentration in stool	enzyme-linked immunosorbent assay (ELISA)	3 months
Secondary	Calprotectin concentration in stool	enzyme-linked immunosorbent assay (ELISA)	baseline
Secondary	Calprotectin concentration in stool	enzyme-linked immunosorbent assay (ELISA)	1 month
Secondary	Calprotectin concentration in stool	enzyme-linked immunosorbent assay (ELISA)	3 months
Secondary	Lipopolysaccharide concentration in blood	enzyme-linked immunosorbent assay (ELISA)	baseline
Secondary	Lipopolysaccharide concentration in blood	enzyme-linked immunosorbent assay (ELISA)	1 month
Secondary	Lipopolysaccharide concentration in blood	enzyme-linked immunosorbent assay (ELISA)	3 months
Secondary	Adiposity	Fat mass/fat free mass evaluated by bioimpedance	baseline
Secondary	Adiposity	Fat mass/fat free mass evaluated by bioimpedance	1 month
Secondary	Adiposity	Fat mass/fat free mass evaluated by bioimpedance	3 months
Secondary	Obesity	Body weight	baseline
Secondary	Obesity	Body weight	1 month
Secondary	Obesity	Body weight	3 months
Secondary	Dietary habits	the frequency of certain food consumption (rank score) by means of validated Food Frequency Questionnaire (FFQ).	baseline
Secondary	Physical activity	International Physical Activity Questionnaire. Results can be reported in categories (low activity levels, moderate activity levels or high activity levels) or as a continuous variable (MET minutes a week).	baseline
Secondary	Functions of peripheral blood mononuclear cells (PBMCs)	mass cytometry (CyTOF)	baseline
Secondary	Functions of peripheral blood mononuclear cells (PBMCs)	mass cytometry (CyTOF)	1 month
Secondary	Functions of peripheral blood mononuclear cells (PBMCs)	mass cytometry (CyTOF)	3 months
Secondary	Insulin resistance	HOMA-Homeostasis Model Assessment calculated from fasted glycemia and insulinemia	baseline
Secondary	Insulin resistance	HOMA-Homeostasis Model Assessment calculated from fasted glycemia and insulinemia	1 month
Secondary	Insulin resistance	HOMA-Homeostasis Model Assessment calculated from fasted glycemia and insulinemia	3 months
Secondary	carbohydrate metabolism	glycated hemoglobin (HbA1c)	baseline
Secondary	carbohydrate metabolism	glycated hemoglobin (HbA1c)	1 month
Secondary	carbohydrate metabolism	glycated hemoglobin (HbA1c)	3 months
Secondary	Concentration of blood lipids	Analysis of circulating lipids : total, LDL and HDL cholesterol (mg/dl), triglycerides (md/dl)	baseline
Secondary	Concentration of blood lipids	Analysis of circulating lipids : total, LDL and HDL cholesterol (mg/dl), triglycerides (md/dl)	1 month
Secondary	Concentration of blood lipids	Analysis of circulating lipids : total, LDL and HDL cholesterol (mg/dl), triglycerides (md/dl)	3 months

External Links

•   EC official website with research results