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Clinical Trials/NCT05738746
NCT05738746
Completed
Not Applicable

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

Pomeranian Medical University Szczecin2 sites in 1 country202 target enrollmentOctober 24, 2023

Overview

Phase
Not Applicable
Intervention
Not specified
Conditions
Stress
Sponsor
Pomeranian Medical University Szczecin
Enrollment
202
Locations
2
Primary Endpoint
Cardiovascular marker of stressor intensity
Status
Completed
Last Updated
last year

Overview

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.

Registry
clinicaltrials.gov
Start Date
October 24, 2023
End Date
March 10, 2025
Last Updated
last year
Study Type
Interventional
Study Design
Parallel
Sex
All

Investigators

Sponsor
Pomeranian Medical University Szczecin
Responsible Party
Sponsor

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;

Outcomes

Primary Outcomes

Cardiovascular marker of stressor intensity

Time Frame: 3 months

heart rate

Stress intensity

Time Frame: 3 months

Perceived Stress Scale (PSS-10). Individual scores on the PSS can range from 0 to 40 with higher scores indicating higher perceived stress.

Occurrence of Irritable Bowel Syndrome

Time Frame: 3 months

Rome IV criteria

Psychosocial working conditions

Time Frame: 3 months

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

The recognition of the most common mental disorders

Time Frame: 3 months

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

Depression

Time Frame: 3 months

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.

Depressive state

Time Frame: 3 months

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.

Anxiety and stress

Time Frame: 3 months

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 1. - Applied to me to some degree, or some of the time 2. - Applied to me to a considerable degree, or a good part of time 3. - 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

Occurence and severity of gastrointestinal symptoms

Time Frame: 3 months

Gastrointestinal Symptom Rating Scale (GSRS)

Secondary Outcomes

  • Lipopolysaccharide concentration in blood(3 months)
  • Obesity(3 months)
  • Functions of peripheral blood mononuclear cells (PBMCs)(3 months)
  • Adiposity(3 months)
  • carbohydrate metabolism(3 months)
  • Short chain fatty acids content in stool(3 months)
  • Calprotectin concentration in stool(3 months)
  • Microbiota composition(3 months)
  • A. muciniphila count in stool(3 months)
  • Total bacteria count in stool(3 months)
  • Inflammatory mediators concentrations in blood(3 months)
  • Zonulin concentration in stool(3 months)
  • Physical activity(baseline)
  • Insulin resistance(3 months)
  • Immune phenotypes of peripheral blood mononuclear cells (PBMCs)(3 months)
  • Dietary habits(baseline)
  • Concentration of blood lipids(3 months)

Study Sites (2)

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