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Completed

NCT Number: NCT05801042

Effect of Encapsulated Vs Free Probiotic on Brain Function

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.

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Key information

Conditions

Age range

60 year–80 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Örebro University

Örebro, Örebro County, 70182, Sweden

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

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

Exclusion criteria

  • Diagnosis of type 1 and/or type 2 diabetes
  • Current (or within the last 4 weeks prior to study start) use of probiotic supplementation
  • Immobile (defined as the inability to participate in all study-related procedures)
  • History of complicated gastrointestinal surgery
  • Diagnosed inflammatory bowel disease (IBD)
  • Current diagnosis of psychiatric disease/s or syndromes
  • Current diagnosis of neurodegenerative disease
  • Systemic use of antibiotics and/or steroid medication in the last 4 months prior to inclusion
  • Use of any non-steroidal anti-inflammatory drug (NSAID) more than 3 times a week for the last 2 months
  • Consumption of any NSAID within 7 days of study start
  • 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
  • Regular smoking, use of snuff, nicotine, cannabidiol narcotics/supplements, or e-cigarette use
  • Drinking more than 9 standard cups of alcohol per week and/or more than 3 standard cups of alcohol per occasion
  • 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.)
  • After being included in the study, starting any medication or treatment that could potentially influence the study participation and/or study analysis
  • Cerebral bleeding or history of cerebral bleeding
  • Claustrophobia
  • In operated apparatus (e.g., pacemaker), as it interferes with MR imaging
  • Aneurysm clips in the head
  • Shunts in the head
  • Grenade-splinter or metal-splinter in the body (e.g., eyes)
  • Metal or electrodes in the body (e.g., temp-catheter, aorta stent, cochlear implant)
  • Comprehensive tooth-implants or prosthesis
  • Operated in the head
  • Operated in the heart
  • Swallowed a video-capsule, which may still be in the GI tract
  • Left-handed

Treatment and study plan

Maltodextrin

Dietary Supplement

Placebo product

Encapsulated Lactocaseibacillus rhamnosus

Dietary Supplement

Probiotic product

Non-encapsulated Lactocaseibacillus rhamnosus

Dietary Supplement

Probiotic product

Primary outcomes

  1. Brain functional connectivity as measured by resting-state functional magnetic resonance imaging (fMRI)

    Time frame: 6 weeks

    corrected for baseline

Secondary outcomes

  1. Levels of inhibitory neurotransmitter gamma-aminobutyric acid (GABA) in the brain using MR spectroscopy (MRS)

    Time frame: 6 weeks

    corrected for baseline

  2. Cognitive function assessment using the trail making test (TMT)

    Time frame: 6 weeks

    corrected for baseline, scale 0-400 seconds and number of errors, higher scores indicate worse cognition

  3. Cognitive function assessment using digit symbol substitution test (TMT)

    Time frame: 6 weeks

    corrected for baseline, scale 0-93 points, higher scores indicate better cognition

  4. Cognitive function assessment using letter digit substitution test

    Time frame: 6 weeks

    corrected for baseline, scale 0-135 points, higher scores indicate better cognition

  5. Cognitive function assessment using letter comparison test

    Time frame: 6 weeks

    corrected for baseline, scale 0-42 points, higher scores indicate better cognition

  6. Cognitive function assessment using Rey-Auditory Verbal Learning Test

    Time frame: 6 weeks

    corrected for baseline, scale 0-120 points, higher scores indicate better cognition

  7. Cognitive function assessment using N-back task

    Time frame: 6 weeks

    corrected for baseline, higher scores indicate better cognition

  8. Cognitive function assessment using Face-Name Paired Associate Task (FNPA)

    Time frame: 6 weeks

    corrected for baseline, higher scores indicate better cognition

  9. Levels of inflammatory markers (e.g. high sensitivity C-reactive protein (hsCRP), interleukin (IL)-6, tumor necrosis factor (TNF)-alpha)

    Time frame: 6 weeks

    corrected for baseline, unit of measurement concentration given as mg/ml

  10. Levels of inflammatory markers (e.g. high sensitivity C-reactive protein (hsCRP), interleukin (IL)-6, tumor necrosis factor (TNF)-alpha)

    Time frame: 3 weeks

    corrected for baseline, unit of measurement concentration given as mg/ml

  11. Levels of metabolic blood markers (blood fats)

    Time frame: 6 weeks

    corrected for baseline, unit of measurement concentration given as mg/ml

  12. Levels of metabolic blood markers (blood fats)

    Time frame: 3 weeks

    corrected for baseline, unit of measurement concentration given as mg/ml

  13. Levels of neural blood markers (brain derived neurotrophic factor (BDNF), serotonin)

    Time frame: 6 weeks

    corrected for baseline, unit of measurement concentration given as mg/ml

  14. Levels of neural blood markers (brain derived neurotrophic factor (BDNF), serotonin)

    Time frame: 3 weeks

    corrected for baseline, unit of measurement concentration given as mg/ml

  15. Characterisation of lymphocyte subpopulations using flow cytometry

    Time frame: 6 weeks

    corrected for baseline

  16. Faecal samples for evaluation of gut microbiota composition via next-generation sequencing (NGS)

    Time frame: 6 weeks

    corrected for baseline

Other outcomes

  1. Brain stem functional connectivity as measured by resting-state functional magnetic resonance imaging (fMRI)

    Time frame: 6 weeks

    corrected for baseline

  2. Brain structure measured by magnetic resonance imaging (fMRI)

    Time frame: 6 weeks

    corrected for baseline

  3. Characterisation of probiotic bacteria in faecal samples using flow cytometry

    Time frame: 6 weeks

    corrected for baseline

  4. Assessment of psychological health using Hospital Anxiety and Depression Scale (HADS)

    Time frame: 3 weeks

    corrected for baseline, scale 0-42, higher score indicates worse anxiety and depression symptoms

  5. Assessment of psychological health using Hospital Anxiety and Depression Scale (HADS)

    Time frame: 6 weeks

    corrected for baseline, scale 0-42, higher score indicates worse anxiety and depression symptoms

  6. Assessment of psychological health using Pittsburgh Sleep Quality Index (PSQI)

    Time frame: 3 weeks

    corrected for baseline, scale 0-21, higher score indicates worse sleep

  7. Assessment of psychological health using Pittsburgh Sleep Quality Index (PSQI)

    Time frame: 6 weeks

    corrected for baseline, scale 0-21, higher score indicates worse sleep

  8. Assessment of psychological health using Perceived Stress Scale (PSS)

    Time frame: 3 weeks

    corrected for baseline, scale 0-40, higher score indicates more perceived stress

  9. Assessment of psychological health using Perceived Stress Scale (PSS)

    Time frame: 6 weeks

    corrected for baseline, scale 0-40, higher score indicates more perceived stress

  10. Assessment of gastrointestinal health using Gastrointestinal Symptoms Rating Scale (GSRS)

    Time frame: 3 weeks

    corrected for baseline, scale 15-105, higher score indicates more gastrointestinal symptoms

  11. Assessment of gastrointestinal health using Gastrointestinal Symptoms Rating Scale (GSRS)

    Time frame: 6 weeks

    corrected for baseline, scale 15-105, higher score indicates more gastrointestinal symptoms

  12. Cognitive function assessment using the Montreal Cognitive Assessment (MoCA)

    Time frame: 6 weeks

    corrected for baseline, scale 0-30 points, higher scores indicate better cognition

  13. Brain functional connectivity as measured by resting-state functional magnetic resonance imaging (fMRI)

    Time frame: 10-12 weeks

    corrected for baseline

  14. Assessment of psychological health using Hospital Anxiety and Depression Scale (HADS)

    Time frame: 10-12 weeks

    corrected for baseline, scale 0-42, higher score indicates worse anxiety and depression symptoms

  15. Assessment of psychological health using Pittsburgh Sleep Quality Index (PSQI)

    Time frame: 10-12 weeks

    corrected for baseline, scale 0-21, higher score indicates worse sleep

  16. Assessment of psychological health using Perceived Stress Scale (PSS)

    Time frame: 10-12 weeks

    corrected for baseline, scale 0-40, higher score indicates more perceived stress

  17. Assessment of gastrointestinal health using Gastrointestinal Symptoms Rating Scale (GSRS)

    Time frame: 10-12 weeks

    corrected for baseline, scale 15-105, higher score indicates more gastrointestinal symptoms

  18. Brain structure measured by magnetic resonance imaging (fMRI)

    Time frame: 10-12 weeks

    corrected for baseline

Sponsors and collaborators

Lead sponsor

Robert Brummer

Other

Registry information

Official study title

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

Important dates

Study start
2023
Primary completion
2023
Study completion
2024
First posted
Apr 6, 2023
Registry last updated
Oct 8, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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