Clinical trial NCT05738746: The Efficacy of Pasteurised Akkermansia Muciniphila in Healthy Medical Workers
Official title: The Effects of the Anti-inflammatory Microbe - Pasteurized Akkermansia Muciniphila (PAM) on Symptoms of Somatic and Mental Stress in Healthcare Professionals
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Stress
Healthy
Dietary Supplement
Keywords: microbiota
postbiotic
stress
metabolome
immunometabolism
Lead sponsor: Pomeranian Medical University Szczecin
Sponsor class: OTHER
Collaborators: name: SANPROBI SPOLKA Z OGRANICZONA ODPOWIEDZIALNOSCIA SPOLKA KOMANDYTOWA
name: THE AKKERMANSIA COMPANY
name: Charite University, Berlin, Germany
name: MAX DELBRUECK CENTRUM FUER MOLEKULARE MEDIZIN IN DER HELMHOLTZ-GEMEINSCHAFT (MDC) - MDC
name: Imperial College London
First posted: 2023-02-22
Enrollment: 202
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: parallel-groups, randomized, placebo-controlled clinical study
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Stress intensity
timeFrame: baseline
measure: Stress intensity
timeFrame: 1 month
measure: Stress intensity
timeFrame: 3 months
measure: Cardiovascular marker of stressor intensity
timeFrame: baseline
measure: Cardiovascular marker of stressor intensity
timeFrame: 1 month
measure: Cardiovascular marker of stressor intensity
timeFrame: 3 months
measure: Cardiovascular marker of stressor intensity
timeFrame: baseline
measure: Cardiovascular marker of stressor intensity
timeFrame: 1 month
measure: Cardiovascular marker of stressor intensity
timeFrame: 3 months
measure: Stress intensity
timeFrame: baseline
measure: Stress intensity
timeFrame: 1 month
measure: Stress intensity
timeFrame: 3 months
measure: Psychosocial working conditions
timeFrame: baseline
measure: Psychosocial working conditions
timeFrame: 1 month
measure: Psychosocial working conditions
timeFrame: 3 months
measure: The recognition of the most common mental disorders
timeFrame: baseline
measure: The recognition of the most common mental disorders
timeFrame: 1 month
measure: The recognition of the most common mental disorders
timeFrame: 3 months
measure: Depression
timeFrame: baseline
measure: Depression
timeFrame: 1 month
measure: Depression
timeFrame: 3 months
measure: Depressive state
timeFrame: baseline
measure: Depressive state
timeFrame: 1 month
measure: Depressive state
timeFrame: 3 months
measure: Anxiety and stress
timeFrame: baseline
measure: Anxiety and stress
timeFrame: 1 month
measure: Anxiety and stress
timeFrame: 3 months
measure: Occurrence of Irritable Bowel Syndrome
timeFrame: baseline
measure: Occurrence of Irritable Bowel Syndrome
timeFrame: 1 month
measure: Occurrence of Irritable Bowel Syndrome
timeFrame: 3 months
measure: Occurence and severity of gastrointestinal symptoms
timeFrame: baseline
measure: Occurence and severity of gastrointestinal symptoms
timeFrame: 1 month
measure: Occurence and severity of gastrointestinal symptoms
timeFrame: 3 months
Secondary outcomes:
measure: Microbiota composition
timeFrame: baseline
measure: Microbiota composition
timeFrame: 1 month
measure: Microbiota composition
timeFrame: 3 months
measure: A. muciniphila count in stool
timeFrame: baseline
measure: A. muciniphila count in stool
timeFrame: 1 month
measure: A. muciniphila count in stool
timeFrame: 3 months
measure: Total bacteria count in stool
timeFrame: baseline
measure: Total bacteria count in stool
timeFrame: 1 month
measure: Total bacteria count in stool
timeFrame: 3 months
measure: Short chain fatty acids content in stool
timeFrame: baseline
measure: Short chain fatty acids content in stool
timeFrame: 1 month
measure: Short chain fatty acids content in stool
timeFrame: 3 months
measure: Immune phenotypes of peripheral blood mononuclear cells (PBMCs)
timeFrame: baseline
measure: Immune phenotypes of peripheral blood mononuclear cells (PBMCs)
timeFrame: 1 month
measure: Immune phenotypes of peripheral blood mononuclear cells (PBMCs)
timeFrame: 3 months
measure: Inflammatory mediators concentrations in blood
timeFrame: baseline
measure: Inflammatory mediators concentrations in blood
timeFrame: 1 month
measure: Inflammatory mediators concentrations in blood
timeFrame: 3 months
measure: Zonulin concentration in stool
timeFrame: baseline
measure: Zonulin concentration in stool
timeFrame: 1 month
measure: Zonulin concentration in stool
timeFrame: 3 months
measure: Calprotectin concentration in stool
timeFrame: baseline
measure: Calprotectin concentration in stool
timeFrame: 1 month
measure: Calprotectin concentration in stool
timeFrame: 3 months
measure: Lipopolysaccharide concentration in blood
timeFrame: baseline
measure: Lipopolysaccharide concentration in blood
timeFrame: 1 month
measure: Lipopolysaccharide concentration in blood
timeFrame: 3 months
measure: Adiposity
timeFrame: baseline
measure: Adiposity
timeFrame: 1 month
measure: Adiposity
timeFrame: 3 months
measure: Obesity
timeFrame: baseline
measure: Obesity
timeFrame: 1 month
measure: Obesity
timeFrame: 3 months
measure: Dietary habits
timeFrame: baseline
measure: Physical activity
timeFrame: baseline
measure: Functions of peripheral blood mononuclear cells (PBMCs)
timeFrame: baseline
measure: Functions of peripheral blood mononuclear cells (PBMCs)
timeFrame: 1 month
measure: Functions of peripheral blood mononuclear cells (PBMCs)
timeFrame: 3 months
measure: Insulin resistance
timeFrame: baseline
measure: Insulin resistance
timeFrame: 1 month
measure: Insulin resistance
timeFrame: 3 months
measure: carbohydrate metabolism
timeFrame: baseline
measure: carbohydrate metabolism
timeFrame: 1 month
measure: carbohydrate metabolism
timeFrame: 3 months
measure: Concentration of blood lipids
timeFrame: baseline
measure: Concentration of blood lipids
timeFrame: 1 month
measure: Concentration of blood lipids
timeFrame: 3 months
Other outcomes:
Locations:
city: Szczecin
country: Poland
facility: Pomeranian Medical University in Szczecin
state: Zachodniopomorskie
city: Szczecin
country: Poland
facility: Center fo Medical Simulation
state: Zachodniopomorskie
Study officials:
References:
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.
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.
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.
citation: 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.