Effect of Encapsulated vs Free Probiotic on Brain Function

Comparing the Efficacy of Micro-encapsulated Lactocaseibacillus Rhamnosus vs Free Probiotic in Powder to Affect Brain Connectivity

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Aging
• Intervention / Treatment: Dietary supplement: Encapsulated Lactocaseibacillus rhamnosus; Dietary supplement: Non-encapsulated Lactocaseibacillus rhamnosus; Dietary supplement: Maltodextrin

• Study Type: Interventional
• Enrollment (Estimated): 90
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Robert JM Brummer, MD PhD; Phone Number: 004619303731; Email: Robert.brummer@oru.se

Study Locations

• Sweden
  • Örebro, Sweden, 70182
    • Örebro University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Dietary supplement: Maltodextrin; Placebo product
Experimental: Encapsulated probiotic	Dietary supplement: Encapsulated Lactocaseibacillus rhamnosus; Probiotic product
Active Comparator: Non-encapsulated probiotic	Dietary supplement: Non-encapsulated Lactocaseibacillus rhamnosus; Probiotic product

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Brain functional connectivity as measured by resting-state functional magnetic resonance imaging (fMRI)	corrected for baseline	6 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Levels of inhibitory neurotransmitter gamma-aminobutyric acid (GABA) in the brain using MR spectroscopy (MRS)	corrected for baseline	6 weeks
Cognitive function assessment using the trail making test (TMT)	corrected for baseline, scale 0-400 seconds and number of errors, higher scores indicate worse cognition	6 weeks
Cognitive function assessment using digit symbol substitution test (TMT)	corrected for baseline, scale 0-93 points, higher scores indicate better cognition	6 weeks
Cognitive function assessment using letter digit substitution test	corrected for baseline, scale 0-135 points, higher scores indicate better cognition	6 weeks
Cognitive function assessment using letter comparison test	corrected for baseline, scale 0-42 points, higher scores indicate better cognition	6 weeks
Cognitive function assessment using Rey-Auditory Verbal Learning Test	corrected for baseline, scale 0-120 points, higher scores indicate better cognition	6 weeks
Cognitive function assessment using N-back task	corrected for baseline, higher scores indicate better cognition	6 weeks
Cognitive function assessment using Face-Name Paired Associate Task (FNPA)	corrected for baseline, higher scores indicate better cognition	6 weeks
Levels of inflammatory markers (e.g. high sensitivity C-reactive protein (hsCRP), interleukin (IL)-6, tumor necrosis factor (TNF)-alpha)	corrected for baseline, unit of measurement concentration given as mg/ml	6 weeks
Levels of inflammatory markers (e.g. high sensitivity C-reactive protein (hsCRP), interleukin (IL)-6, tumor necrosis factor (TNF)-alpha)	corrected for baseline, unit of measurement concentration given as mg/ml	3 weeks
Levels of metabolic blood markers (blood fats)	corrected for baseline, unit of measurement concentration given as mg/ml	6 weeks
Levels of metabolic blood markers (blood fats)	corrected for baseline, unit of measurement concentration given as mg/ml	3 weeks
Levels of neural blood markers (brain derived neurotrophic factor (BDNF), serotonin)	corrected for baseline, unit of measurement concentration given as mg/ml	6 weeks
Levels of neural blood markers (brain derived neurotrophic factor (BDNF), serotonin)	corrected for baseline, unit of measurement concentration given as mg/ml	3 weeks
Characterisation of lymphocyte subpopulations using flow cytometry	corrected for baseline	6 weeks
Faecal samples for evaluation of gut microbiota composition via next-generation sequencing (NGS)	corrected for baseline	6 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Brain stem functional connectivity as measured by resting-state functional magnetic resonance imaging (fMRI)	corrected for baseline	6 weeks
Brain structure measured by magnetic resonance imaging (fMRI)	corrected for baseline	6 weeks
Characterisation of probiotic bacteria in faecal samples using flow cytometry	corrected for baseline	6 weeks
Assessment of psychological health using Hospital Anxiety and Depression Scale (HADS)	corrected for baseline, scale 0-42, higher score indicates worse anxiety and depression symptoms	3 weeks
Assessment of psychological health using Hospital Anxiety and Depression Scale (HADS)	corrected for baseline, scale 0-42, higher score indicates worse anxiety and depression symptoms	6 weeks
Assessment of psychological health using Pittsburgh Sleep Quality Index (PSQI)	corrected for baseline, scale 0-21, higher score indicates worse sleep	3 weeks
Assessment of psychological health using Pittsburgh Sleep Quality Index (PSQI)	corrected for baseline, scale 0-21, higher score indicates worse sleep	6 weeks
Assessment of psychological health using Perceived Stress Scale (PSS)	corrected for baseline, scale 0-40, higher score indicates more perceived stress	3 weeks
Assessment of psychological health using Perceived Stress Scale (PSS)	corrected for baseline, scale 0-40, higher score indicates more perceived stress	6 weeks
Assessment of gastrointestinal health using Gastrointestinal Symptoms Rating Scale (GSRS)	corrected for baseline, scale 15-105, higher score indicates more gastrointestinal symptoms	3 weeks
Assessment of gastrointestinal health using Gastrointestinal Symptoms Rating Scale (GSRS)	corrected for baseline, scale 15-105, higher score indicates more gastrointestinal symptoms	6 weeks
Cognitive function assessment using the Montreal Cognitive Assessment (MoCA)	corrected for baseline, scale 0-30 points, higher scores indicate better cognition	6 weeks
Brain functional connectivity as measured by resting-state functional magnetic resonance imaging (fMRI)	corrected for baseline	10-12 weeks
Assessment of psychological health using Hospital Anxiety and Depression Scale (HADS)	corrected for baseline, scale 0-42, higher score indicates worse anxiety and depression symptoms	10-12 weeks
Assessment of psychological health using Pittsburgh Sleep Quality Index (PSQI)	corrected for baseline, scale 0-21, higher score indicates worse sleep	10-12 weeks
Assessment of psychological health using Perceived Stress Scale (PSS)	corrected for baseline, scale 0-40, higher score indicates more perceived stress	10-12 weeks
Assessment of gastrointestinal health using Gastrointestinal Symptoms Rating Scale (GSRS)	corrected for baseline, scale 15-105, higher score indicates more gastrointestinal symptoms	10-12 weeks
Brain structure measured by magnetic resonance imaging (fMRI)	corrected for baseline	10-12 weeks

Collaborators and Investigators

• Sponsor: Robert Brummer
• Investigators: Principal Investigator: Robert JM Brummer, MD PhD, Örebro University, Sweden

Study record dates

Study Major Dates

• Study Start (Actual): February 7, 2023
• Primary Completion (Actual): November 10, 2023
• Study Completion (Estimated): June 30, 2024

Study Registration Dates

• First Submitted: February 10, 2023
• First Submitted That Met QC Criteria: April 5, 2023
• First Posted (Actual): April 6, 2023

Study Record Updates

• Last Update Posted (Actual): April 3, 2024
• Last Update Submitted That Met QC Criteria: April 2, 2024
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Other Study ID Numbers: AnaBio

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No