Probiotic Effects on the Microbe-brain-gut Interaction and Brain Activity During Stress Tasks in Healthy Subjects

Magnetic Resonance Imaging Clinical Trial

Official title:

Probiotic Effects on the Microbe-brain-gut Interaction and Brain Activity During Stress Tasks in Healthy Subjects

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03615651
• Other study ID #: 2017/398
• Status: Completed
• Phase: N/A
• Start date: January 22, 2018
• Est. completion date: June 16, 2018

Study information

• Verified date: July 2018
• Source: Örebro University, Sweden
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 22
• Est. completion date: June 16, 2018
• Est. primary completion date: June 16, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Emotional Stress
• Gut Microbiota
• Magnetic Resonance Imaging
• Probiotics
• Stress, Psychological

Intervention

Dietary Supplement:
• Probiotic
The Probiotic Formula is commercially available and contains a combination of 3 probiotic strains in addition to other nutrients. The total daily amount of probiotic strain in the product will be no less than 3 billion colony-forming units (CFU) per 3 g powder sachet.

Other:
• Placebo
Placebo intervention.

Locations

Country	Name	City	State
Sweden	Örebro University, Campus USÖ, Örebro University Hospital	Örebro

Sponsors (2)

Lead Sponsor	Collaborator
Örebro University, Sweden	Pfizer

Country where clinical trial is conducted

Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change in physical activity assessed by an actigraphy watch (actiwatch)	Actigraph data regarding physical activity	Comparing the change in week 0 compared to 4, and 8 compared to 12 (before and in the end of the two intervention periods)
Other	Change in sleep quality assessed by an actigraphy watch (actiwatch)	Actigraph data regarding sleep quality	Comparing the change in week 0 compared to 4, and 8 compared to 12 (before and in the end of the two intervention periods)
Other	Change in daily stress levels assessed by an actigraphy watch (actiwatch)	Actigraph data regarding daily stress levels	Comparing the change in week 0 compared to 4, and 8 compared to 12 (before and in the end of the two intervention periods)
Other	Autonomous Nervous System (ANS) Activity, Biopac	ANS activity is measures during stressful tasks.	Comparing the change in week 0 compared to 4, and 8 compared to 12 (before and in the end of the two intervention periods)
Other	Stroop test	The Stroop test is performed for stress induction	Comparing the change in week 0 compared to 4, and 8 compared to 12 (before and in the end of the two intervention periods)
Other	HADS (Hospital Anxiety and Depression Scale)	Hospital Anxiety and Depression Scale, min score 0, max score 3, total score max 42, subscale anxiety max 21, subscale depression max 21	Measured weekly, week 1-12
Other	STAI (State and Trait Anxiety Inventory for Adults)	State and Trait Anxiety Inventory for Adults	Measured weekly, week 1-12
Other	PSS (Perceived Stress Scale)	Perceived Stress Scale, min score 0, max score 40	Measured weekly, week 1-12
Other	Euro-QoL	Euro Qol- Health-related Quality of Life 5Q-5D-5L, min score 0, max score 20, subscale 0-100	Measured weekly, week 1-12
Other	Karolinska Sleep Diary (KSD)	KSD measures sleep quality in the morning	Measured daily, week 1-4 and 8-12
Other	Karolinska Diary of Workload (KDW)	KDW measures workload daily in the evening	Measured daily, week 1-4 and 8-12
Other	Cortisol levels during fMRI tasks (Saliva)	Saliva samples are collected during fMRI to assess cortisol levels	Comparing week 4 and 12
Other	Cortisol awakening rhythm (saliva)	Saliva samples are collected at home (3 days á 5 samples) to assess cortisol levels	Comparing the change in week 0 compared to 4, and 8 compared to 12 (before and in the end of the two intervention periods)
Other	Faecal samples	Faecal samples will be analyzed for quantitative and qualitative microbial composition by 16S rRNA-based next generation sequencing (NGS)	Comparing the change in week 0 compared to 4, and 8 compared to 12 (before and in the end of the two intervention periods)
Other	Change in inflammatory markers	Blood samples will be collected after each intervention period to assess inflammatory markers using Enzyme-Linked Immunosorbent Assays (ELISA)s	Comparing the change in week 0 compared to 4, and 8 compared to 12 (before and in the end of the two intervention periods)
Primary	Change in brain response to validated emotional challenge task (EAT) during functional brain imaging		Comparing week 4 and 12
Secondary	Change in brain response to a cognitive challenge task (MIST) during functional brain imaging		Comparing week 4 and 12