Clinical trial NCT03615651: Probiotic Effects on the Microbe-brain-gut Interaction and Brain Activity During Stress Tasks in Healthy Subjects
Official title: Probiotic Effects on the Microbe-brain-gut Interaction and Brain Activity During Stress Tasks in Healthy Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Probiotics
Gut Microbiota
Emotional Stress
Magnetic Resonance Imaging
Lead sponsor: Örebro University, Sweden
Sponsor class: OTHER
Collaborators: name: Pfizer
First posted: 2018-08-06
Enrollment: 22
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief summary: The aim of this study is to determine if and how the "Probiotic Product" affects functional brain responses in healthy subjects during an emotional- and arithmetic stress task, respectively and in terms of microbe-brain-gut interactions.

Detailed description: The aim of this study is to determine if and how the "Probiotic Product" affects functional brain responses in healthy subjects during an emotional- and arithmetic stress task, respectively and in terms of microbe-brain-gut interactions.

In this randomized double-blind placebo-controlled study, n=22 healthy subjects will receive the following interventions in a crossover fashion, separated by a 4-week wash-out period: 1) Probiotic Formula, 2) placebo. After baseline assessments, study participants will start with a 4-week intervention with the study product or the placebo, followed by a 4-week wash-out period and a subsequent 4-week intervention period (placebo or study product, respectively). fMRI (functional magnetic resonance imaging) scanning during two validated stress tasks will be performed after each of the intervention periods (week 4 and week 12). At the same time points and in addition on the days before the 1st and 2nd intervention (baseline 1 and 2), saliva, blood and faecal samples will be collected. Questionnaire data will be collected and psychological tests and instruments will be performed. For one week at baseline and during the intervention periods (last week), subjects will wear actigraphs to record their physical activity and help assess sleep quality. At baseline, subjects will undergo a carbon dioxide (CO2) challenge test as well as a food diary to record dietary habits.

Eligibility criteria: Inclusion Criteria:

1. Age: Age: 18-65 years, males/females.
2. Signed informed consent -

Exclusion Criteria:

1. Concurrent or recent treatment with drugs affecting intestinal function or mood, e.g., antidepressants (\< 12 weeks) or antibiotics (\< 12 weeks).
2. Concurrent or recent (\< 4 weeks) use of nutritional supplements or herb products affecting intestinal function or mood (e.g. aloe vera, St. John´s Wort, fibers, prebiotics and probiotics).
3. Diagnosis of major psychiatric or somatic disease. 4) Abuse of alcohol or drugs. 5) Recent (\< 4 weeks) intake of proton pump inhibitors, proton pump inhibitors, PPIs (e.g., omeprazole).

6) Asthma. 7) Cardiovascular diseases. 8) Epilepsy. 9) Renal failure. 10) Cerebral bleeding or history of cerebral bleeding. 11) Allergic to latex. 12) Pregnancy (assessed by urine test) or breastfeeding. 13) Claustrophobia. 14) Smoking or using tobacco including snuff. 15) Inability to maintain exercise routine and dietary pattern during the study.

16) Consumption of more than 6 cups of coffee/caffeine-containing beverages per day.

17) Professional athlete. 18) Dominant left-hand. 19) Medical implant (e.g., pacemaker). 20) Aneurysm clips in the head. 21) Shunts in the head. 22) Grenade-splinter or metal-splinter in the body (e.g., eyes). 23) Metal or electrodes in the body (e.g., temp-catheter, aorta stent, cochlea implant).

24) Comprehensive tooth-implants or prothesis. 25) Operated in the head. 26) Operated in the heart. 27) Swallowed a video-capsule. 28) Non-corrected astigmatism. 29) Regular intake of systemic corticosteroids and anti-inflammatory medication (including NSAIDs) during the last three months.

30) Visual defect without possibility to use lenses during MRI scanning. 31) Known allergy to milk or soy. 32) Any other reason the investigator feels the subject is not suitable for participation in the study.

Primary outcomes:
measure: Change in brain response to validated emotional challenge task (EAT) during functional brain imaging
timeFrame: Comparing week 4 and 12
Secondary outcomes:
measure: Change in brain response to a cognitive challenge task (MIST) during functional brain imaging
timeFrame: Comparing week 4 and 12
Other outcomes:
measure: Change in physical activity assessed by an actigraphy watch (actiwatch)
timeFrame: Comparing the change in week 0 compared to 4, and 8 compared to 12 (before and in the end of the two intervention periods)
measure: Change in sleep quality assessed by an actigraphy watch (actiwatch)
timeFrame: Comparing the change in week 0 compared to 4, and 8 compared to 12 (before and in the end of the two intervention periods)
measure: Change in daily stress levels assessed by an actigraphy watch (actiwatch)
timeFrame: Comparing the change in week 0 compared to 4, and 8 compared to 12 (before and in the end of the two intervention periods)
measure: Autonomous Nervous System (ANS) Activity, Biopac
timeFrame: Comparing the change in week 0 compared to 4, and 8 compared to 12 (before and in the end of the two intervention periods)
measure: Stroop test
timeFrame: Comparing the change in week 0 compared to 4, and 8 compared to 12 (before and in the end of the two intervention periods)
measure: HADS (Hospital Anxiety and Depression Scale)
timeFrame: Measured weekly, week 1-12
measure: STAI (State and Trait Anxiety Inventory for Adults)
timeFrame: Measured weekly, week 1-12
measure: PSS (Perceived Stress Scale)
timeFrame: Measured weekly, week 1-12
measure: Euro-QoL
timeFrame: Measured weekly, week 1-12
measure: Karolinska Sleep Diary (KSD)
timeFrame: Measured daily, week 1-4 and 8-12
measure: Karolinska Diary of Workload (KDW)
timeFrame: Measured daily, week 1-4 and 8-12
measure: Cortisol levels during fMRI tasks (Saliva)
timeFrame: Comparing week 4 and 12
measure: Cortisol awakening rhythm (saliva)
timeFrame: Comparing the change in week 0 compared to 4, and 8 compared to 12 (before and in the end of the two intervention periods)
measure: Faecal samples
timeFrame: Comparing the change in week 0 compared to 4, and 8 compared to 12 (before and in the end of the two intervention periods)
measure: Change in inflammatory markers
timeFrame: Comparing the change in week 0 compared to 4, and 8 compared to 12 (before and in the end of the two intervention periods)
Locations:
city: Örebro
country: Sweden
facility: Örebro University, Campus USÖ, Örebro University Hospital
Study officials:
affiliation: Örebro University, Sweden
name: Robert Brummer, Prof
role: PRINCIPAL_INVESTIGATOR
References:
citation: Rode J, Edebol Carlman HMT, Konig J, Repsilber D, Hutchinson AN, Thunberg P, Andersson P, Persson J, Kiselev A, Lathrop Stern L, Salomon B, Mohammed AA, Labus JS, Brummer RJ. Probiotic Mixture Containing Lactobacillus helveticus, Bifidobacterium longum and Lactiplantibacillus plantarum Affects Brain Responses Toward an Emotional Task in Healthy Subjects: A Randomized Clinical Trial. Front Nutr. 2022 Apr 29;9:827182. doi: 10.3389/fnut.2022.827182. eCollection 2022.