Clinical trial NCT05801042: Effect of Encapsulated Vs Free Probiotic on Brain Function
Official title: Comparing the Efficacy of Micro-encapsulated Lactocaseibacillus Rhamnosus Vs Free Probiotic in Powder to Affect Brain Connectivity
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Aging
Lead sponsor: Örebro University, Sweden
Sponsor class: OTHER
First posted: 2023-04-06
Enrollment: 91
Sex: ALL
Minimum age (years): 60
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief summary: Aging is associated with changes in a wide variety of brain networks, including the default mode, saliency attention, and visual networks. Furthermore, current research suggests that a relationship exists between functional connectivity at rest and cognition. Lactocaseibacillus rhamnosus is an ideal strain for the intervention, as it has been show to affect the gut-brain axis, brain function, and behavior. Therefore, the investigators plan to assess resting state functional magnetic resonance imaging (fMRI) to compare changes in brain connectivity between the groups receiving the encapsulate and non-encapsulated Lactocaseibacillus rhamnosus supplements.


Eligibility criteria: Inclusion Criteria:

1. Signed informed consent prior to any study-related procedure
2. Age 60-80 years-old
3. Normal weight at the screening defined as BMI range 18.5-31.9
4. Willing to abstain from regular consumption of probiotic supplements or food products containing probiotic bacteria (including fermented food and beverages)
5. Willing to abstain from regular consumption of supplements and medications known to alter gastrointestinal function or inflammatory status during the study

Exclusion Criteria:

1. Diagnosis of type 1 and/or type 2 diabetes
2. Current (or within the last 4 weeks prior to study start) use of probiotic supplementation
3. Immobile (defined as the inability to participate in all study-related procedures)
4. History of complicated gastrointestinal surgery
5. Diagnosed inflammatory bowel disease (IBD)
6. Current diagnosis of psychiatric disease/s or syndromes
7. Current diagnosis of neurodegenerative disease
8. Systemic use of antibiotics and/or steroid medication in the last 4 months prior to inclusion
9. Use of any non-steroidal anti-inflammatory drug (NSAID) more than 3 times a week for the last 2 months
10. Consumption of any NSAID within 7 days of study start
11. Any condition which could substantially interfere with intestinal barrier function (e.g. gluten sensitivity, lactose intolerance, celiac disease, irritable bowel syndrome (IBS), IBD) or in any other way with the outcome of the study, as decided by the principle investigator's discretion
12. Regular smoking, use of snuff, nicotine, cannabidiol narcotics/supplements, or e-cigarette use
13. Drinking more than 9 standard cups of alcohol per week and/or more than 3 standard cups of alcohol per occasion
14. Regular use, for more than three times a week for the last 2 months and/or 7 days prior to inclusion, of medications which according to the principal investigator can have an anti-inflammatory effect or affect in any way the intestinal barrier function or have an impact on the study analysis (such as laxatives, anti-diarrheal, anti-cholinergic, etc.)
15. After being included in the study, starting any medication or treatment that could potentially influence the study participation and/or study analysis
16. Cerebral bleeding or history of cerebral bleeding
17. Claustrophobia
18. In operated apparatus (e.g., pacemaker), as it interferes with MR imaging
19. Aneurysm clips in the head
20. Shunts in the head
21. Grenade-splinter or metal-splinter in the body (e.g., eyes)
22. Metal or electrodes in the body (e.g., temp-catheter, aorta stent, cochlear implant)
23. Comprehensive tooth-implants or prosthesis
24. Operated in the head
25. Operated in the heart
26. Swallowed a video-capsule, which may still be in the GI tract
27. Left-handed

Primary outcomes:
measure: Brain functional connectivity as measured by resting-state functional magnetic resonance imaging (fMRI)
timeFrame: 6 weeks
Secondary outcomes:
measure: Levels of inhibitory neurotransmitter gamma-aminobutyric acid (GABA) in the brain using MR spectroscopy (MRS)
timeFrame: 6 weeks
measure: Cognitive function assessment using the trail making test (TMT)
timeFrame: 6 weeks
measure: Cognitive function assessment using digit symbol substitution test (TMT)
timeFrame: 6 weeks
measure: Cognitive function assessment using letter digit substitution test
timeFrame: 6 weeks
measure: Cognitive function assessment using letter comparison test
timeFrame: 6 weeks
measure: Cognitive function assessment using Rey-Auditory Verbal Learning Test
timeFrame: 6 weeks
measure: Cognitive function assessment using N-back task
timeFrame: 6 weeks
measure: Cognitive function assessment using Face-Name Paired Associate Task (FNPA)
timeFrame: 6 weeks
measure: Levels of inflammatory markers (e.g. high sensitivity C-reactive protein (hsCRP), interleukin (IL)-6, tumor necrosis factor (TNF)-alpha)
timeFrame: 6 weeks
measure: Levels of inflammatory markers (e.g. high sensitivity C-reactive protein (hsCRP), interleukin (IL)-6, tumor necrosis factor (TNF)-alpha)
timeFrame: 3 weeks
measure: Levels of metabolic blood markers (blood fats)
timeFrame: 6 weeks
measure: Levels of metabolic blood markers (blood fats)
timeFrame: 3 weeks
measure: Levels of neural blood markers (brain derived neurotrophic factor (BDNF), serotonin)
timeFrame: 6 weeks
measure: Levels of neural blood markers (brain derived neurotrophic factor (BDNF), serotonin)
timeFrame: 3 weeks
measure: Characterisation of lymphocyte subpopulations using flow cytometry
timeFrame: 6 weeks
measure: Faecal samples for evaluation of gut microbiota composition via next-generation sequencing (NGS)
timeFrame: 6 weeks
Other outcomes:
measure: Brain stem functional connectivity as measured by resting-state functional magnetic resonance imaging (fMRI)
timeFrame: 6 weeks
measure: Brain structure measured by magnetic resonance imaging (fMRI)
timeFrame: 6 weeks
measure: Characterisation of probiotic bacteria in faecal samples using flow cytometry
timeFrame: 6 weeks
measure: Assessment of psychological health using Hospital Anxiety and Depression Scale (HADS)
timeFrame: 3 weeks
measure: Assessment of psychological health using Hospital Anxiety and Depression Scale (HADS)
timeFrame: 6 weeks
measure: Assessment of psychological health using Pittsburgh Sleep Quality Index (PSQI)
timeFrame: 3 weeks
measure: Assessment of psychological health using Pittsburgh Sleep Quality Index (PSQI)
timeFrame: 6 weeks
measure: Assessment of psychological health using Perceived Stress Scale (PSS)
timeFrame: 3 weeks
measure: Assessment of psychological health using Perceived Stress Scale (PSS)
timeFrame: 6 weeks
measure: Assessment of gastrointestinal health using Gastrointestinal Symptoms Rating Scale (GSRS)
timeFrame: 3 weeks
measure: Assessment of gastrointestinal health using Gastrointestinal Symptoms Rating Scale (GSRS)
timeFrame: 6 weeks
measure: Cognitive function assessment using the Montreal Cognitive Assessment (MoCA)
timeFrame: 6 weeks
measure: Brain functional connectivity as measured by resting-state functional magnetic resonance imaging (fMRI)
timeFrame: 10-12 weeks
measure: Assessment of psychological health using Hospital Anxiety and Depression Scale (HADS)
timeFrame: 10-12 weeks
measure: Assessment of psychological health using Pittsburgh Sleep Quality Index (PSQI)
timeFrame: 10-12 weeks
measure: Assessment of psychological health using Perceived Stress Scale (PSS)
timeFrame: 10-12 weeks
measure: Assessment of gastrointestinal health using Gastrointestinal Symptoms Rating Scale (GSRS)
timeFrame: 10-12 weeks
measure: Brain structure measured by magnetic resonance imaging (fMRI)
timeFrame: 10-12 weeks
Locations:
city: Örebro
country: Sweden
facility: Örebro University
Study officials:
affiliation: Örebro University, Sweden
name: Robert JM Brummer, MD PhD
role: PRINCIPAL_INVESTIGATOR
References: