The Effects of Microbiological Spectrum Changes to Improve Cognitive Health in Aging Population

NCT05051501 | Completed Phase 2

• 1 other identifier: FV-40032
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 2

Brief Summary

The goal of this project is to develop probiotic dietary supplements intended for the elderly, which can modify the composition of the intestinal microbiota typically occurring in the aging population. According to currently held scientific knowledge, it is postulated that the probiotics-induced normalization of the physiological axis in the brain-intestinal microbiota affects the activity of the nervous system. Thus, normalization of this axis should lead to observable improvements in cognitive functions and quality of life.

Conditions

Memory Deficits; Mood Change; Gut Health; Aging Problems; Aging; Cognitive Decline

Keywords

Probiotics; Microbiome; Gut Microflora; Cognitive Health

Outcome Measures

Primary Outcomes (72)

• Change from baseline cognitive function in the Amnesia Light and Brief Assessment (ALBA) at 3 months

  ALBA is a validated measure assessing memory. The scale spans 0-12 points with higher number of points signifying better outcome

  baseline to 3 months

• Change from baseline cognitive function in the Amnesia Light and Brief Assessment (ALBA) at 6 months

  ALBA is a validated measure assessing memory. The scale spans 0-12 points with higher number of points signifying better outcome

  baseline to 6 months

• Change from 3 months cognitive function in the Amnesia Light and Brief Assessment (ALBA) at 6 months

  ALBA is a validated measure assessing memory. The scale spans 0-12 points with higher number of points signifying better outcome

  3 months to 6 months

• Change from 6 months cognitive function in the Amnesia Light and Brief Assessment (ALBA) at 9 months

  ALBA is a validated measure assessing memory. The scale spans 0-12 points with higher number of points signifying better outcome

  6 months to 9 months

• Difference in cognitive function in the Amnesia Light and Brief Assessment (ALBA) at 3 months between the Probiotics C2P/Placebo and Placebo/C2P Probiotics group

  ALBA is a validated measure assessing memory. The scale spans 0-12 points with higher number of points signifying better outcome

  3 months

• Difference in cognitive function in the Amnesia Light and Brief Assessment (ALBA) at 6 months between the Probiotics C2P/Placebo and Placebo/C2P Probiotics group

  ALBA is a validated measure assessing memory. The scale spans 0-12 points with higher number of points signifying better outcome

  6 months

• Change from baseline cognitive function in the Assessment Battery of Cognition (ABACO) at 3 months

  ABACO is a measure of cognitive function, results are in points and range from 0-35, higher point attainment signals better outcome

  baseline to 3 months

• Change from baseline cognitive function in the Assessment Battery of Cognition (ABACO) at 6 months

  ABACO is a measure of cognitive function, results are in points and range from 0-35, higher point attainment signals better outcome

  baseline to 6 months

• Change from 3 months cognitive function in the Assessment Battery of Cognition (ABACO) at 6 months

  ABACO is a measure of cognitive function, results are in points and range from 0-35, higher point attainment signals better outcome

  3 months to 6 months

• Change from 6 months cognitive function in the Assessment Battery of Cognition (ABACO) at 9 months

  ABACO is a measure of cognitive function, results are in points and range from 0-35, higher point attainment signals better outcome

  6 months to 9 months

• Difference in cognitive function in the Assessment Battery of Cognition (ABACO) at 3 months between the Probiotics C2P/Placebo and Placebo/C2P Probiotics group

  ABACO is a measure of cognitive function, results are in points and range from 0-35, higher point attainment signals better outcome

  3 months

• Difference in cognitive function in the Assessment Battery of Cognition (ABACO) at 6 months between the Probiotics C2P/Placebo and Placebo/C2P Probiotics group

  ABACO is a measure of cognitive function, results are in points and range from 0-35, higher point attainment signals better outcome

  6 months

• Change from baseline cognitive function in Semantic word recollection (category: animals, 1 min) at 3 months

  Semantic word recollection is a measure of cognitive function, results range from 0-cca 40, more points signify better outcome

  baseline to 3 months

• Change from baseline cognitive function in Semantic word recollection (category: animals, 1 min) at 6 months

  Semantic word recollection is a measure of cognitive function, results range from 0-cca 40, more points signify better outcome

  baseline to 6 months

• Change from 3 months cognitive function in Semantic word recollection (category: animals, 1 min) at 6 months

  Semantic word recollection is a measure of cognitive function, results range from 0-cca 40, more points signify better outcome

  3 months to 6 months

• Change from 6 months cognitive function in Semantic word recollection (category: animals, 1 min) at 9 months

  Semantic word recollection is a measure of cognitive function, results range from 0-cca 40, more points signify better outcome

  6 months to 9 months

• Difference in cognitive function in Semantic word recollection (category: animals, 1 min) at 3 months between the Probiotics C2P/Placebo and Placebo/C2P Probiotics group

  Semantic word recollection is a measure of cognitive function, results range from 0-cca 40, more points signify better outcome

  3 months

• Difference in cognitive function in Semantic word recollection (category: animals, 1 min) at 6 months between the Probiotics C2P/Placebo and Placebo/C2P Probiotics group

  Semantic word recollection is a measure of cognitive function, results range from 0-cca 40, more points signify better outcome

  6 months

• Change from baseline cognitive function in Rey Auditory Verbal Learning Test (RAVLT) at 3 months

  RAVLT is a validated measure of cognitive function, it has 8 subscales, each of them ranging from 0-15, measured in raw scores which are connected to age-dependent population norm

  baseline to 3 months

• Change from baseline cognitive function in Rey Auditory Verbal Learning Test (RAVLT) at 6 months

  RAVLT is a validated measure of cognitive function, it has 8 subscales, each of them ranging from 0-15, measured in raw scores which are connected to age-dependent population norm

  baseline to 6 months

• Change from 3 months cognitive function in Rey Auditory Verbal Learning Test (RAVLT) at 6 months

  RAVLT is a validated measure of cognitive function, it has 8 subscales, each of them ranging from 0-15, measured in raw scores which are connected to age-dependent population norm

  3 months to 6 months

• Change from 6 months cognitive function in Rey Auditory Verbal Learning Test (RAVLT) at 9 months

  RAVLT is a validated measure of cognitive function, it has 8 subscales, each of them ranging from 0-15, measured in raw scores which are connected to age-dependent population norm

  6 months to 9 months

• Difference in cognitive function in Rey Auditory Verbal Learning Test (RAVLT) at 3 months between the Probiotics C2P/Placebo and Placebo/C2P Probiotics group

  RAVLT is a validated measure of cognitive function, it has 8 subscales, each of them ranging from 0-15, measured in raw scores which are connected to age-dependent population norm

  3 months

• Difference in cognitive function in Rey Auditory Verbal Learning Test (RAVLT) at 6 months between the Probiotics C2P/Placebo and Placebo/C2P Probiotics group

  RAVLT is a validated measure of cognitive function, it has 8 subscales, each of them ranging from 0-15, measured in raw scores which are connected to age-dependent population norm

  6 months

• Change in baseline cognitive function in Wechsler Adult Intelligence Scale, Third edition (WAIS III) - "Symbols" subtest at 3 months

  The WAIS III, subtest "Symbols" is a validated measure of cognitive function, the point scale ranges from 0-133 with larger point attainment signalling better outcome

  baseline to 3 months

• Change in baseline cognitive function in Wechsler Adult Intelligence Scale, Third edition (WAIS III) - "Symbols" subtest at 6 months

  The WAIS III, subtest "Symbols" is a validated measure of cognitive function, the point scale ranges from 0-133 with larger point attainment signalling better outcome

  baseline to 6 months

• Change in 3 month cognitive function in Wechsler Adult Intelligence Scale, Third edition (WAIS III) - "Symbols" subtest at 6 months

  The WAIS III, subtest "Symbols" is a validated measure of cognitive function, the point scale ranges from 0-133 with larger point attainment signalling better outcome

  3 months to 6 months

• Change in 6 month cognitive function in Wechsler Adult Intelligence Scale, Third edition (WAIS III) - "Symbols" subtest at 9 months

  The WAIS III, subtest "Symbols" is a validated measure of cognitive function, the point scale ranges from 0-133 with larger point attainment signalling better outcome

  6 months to 9 months

• Difference in cognitive function in Wechsler Adult Intelligence Scale, Third edition (WAIS III) - "Symbols" subtest at 3 months between the Probiotics C2P/Placebo and Placebo/C2P Probiotics group

  The WAIS III, subtest "Symbols" is a validated measure of cognitive function, the point scale ranges from 0-133 with larger point attainment signalling better outcome

  3 months

• Difference in cognitive function in Wechsler Adult Intelligence Scale, Third edition (WAIS III) - "Symbols" subtest at 6 months between the Probiotics C2P/Placebo and Placebo/C2P Probiotics group

  The WAIS III, subtest "Symbols" is a validated measure of cognitive function, the point scale ranges from 0-133 with larger point attainment signalling better outcome

  6 months

• Change in baseline cognitive function in Trail Making Test (TMT), Parts A & B at 3 months

  The TMT is a validated measure of cognitive function, the time upon completion is measured

  baseline to 3 months

• Change in baseline cognitive function in Trail Making Test (TMT), Parts A & B at 6 months

  The TMT is a validated measure of cognitive function, the time upon completion is measured

  baseline to 6 months

• Change in 3 month cognitive function in Trail Making Test (TMT), Parts A & B at 6 months

  The TMT is a validated measure of cognitive function, the time upon completion is measured

  3 months to 6 months

• Change in 6 month cognitive function in Trail Making Test (TMT), Parts A & B at 9 months

  The TMT is a validated measure of cognitive function, the time upon completion is measured

  6 months to 9 months

• Difference cognitive function in Trail Making Test (TMT), Parts A & B at 3 months between the Probiotics C2P/Placebo and Placebo/C2P Probiotics group

  The TMT is a validated measure of cognitive function, the time upon completion is measured

  3 months

• Difference cognitive function in Trail Making Test (TMT), Parts A & B at 6 months between the Probiotics C2P/Placebo and Placebo/C2P Probiotics group

  The TMT is a validated measure of cognitive function, the time upon completion is measured

  6 months

• Change in baseline mood in Geriatric Depression Scale at 3 months.

  A self-report measure of mood, measured on 0-15 point scale, higher point attainment signifies worse outcome

  baseline to 3 months

• Change in baseline mood in Geriatric Depression Scale at 6 months.

  A self-report measure of mood, measured on 0-15 point scale, higher point attainment signifies worse outcome

  baseline to 6 months

• Change in 3 month mood in Geriatric Depression Scale at 6 months.

  A self-report measure of mood, measured on 0-15 point scale, higher point attainment signifies worse outcome

  3 months to 6 months

• Change in 6 month mood in Geriatric Depression Scale at 9 months.

  A self-report measure of mood, measured on 0-15 point scale, higher point attainment signifies worse outcome

  6 months to 9 months

• Difference in mood in Geriatric Depression Scale at 3 months between the Probiotics C2P/Placebo and Placebo/C2P Probiotics group

  A self-report measure of mood, measured on 0-15 point scale, higher point attainment signifies worse outcome

  3 months

• Difference in mood in Geriatric Depression Scale at 6 months between the Probiotics C2P/Placebo and Placebo/C2P Probiotics group

  A self-report measure of mood, measured on 0-15 point scale, higher point attainment signifies worse outcome

  6 months

• Change from baseline self-sufficiency self-reported in Questionnaire of functional state (abbreviation in original language: subjective FAQ-CZ) at 3 months

  FAQ-CZ is a self-report measure of self-sufficiency, it is measured on a scale of 0-30 with higher point attainment signalling worse outcome

  baseline to 3 months

• Change from baseline self-sufficiency self-reported in Questionnaire of functional state (abbreviation in original language: subjective FAQ-CZ) at 6 months

  FAQ-CZ is a self-report measure of self-sufficiency, it is measured on a scale of 0-30 with higher point attainment signalling worse outcome

  baseline to 6 months

• Change from 3 month self-sufficiency self-reported in Questionnaire of functional state (abbreviation in original language: subjective FAQ-CZ) at 6 months

  FAQ-CZ is a self-report measure of self-sufficiency, it is measured on a scale of 0-30 with higher point attainment signalling worse outcome

  3 months to 6 months

• Change from 6 month self-sufficiency self-reported in Questionnaire of functional state (abbreviation in original language: subjective FAQ-CZ) at 9 months

  FAQ-CZ is a self-report measure of self-sufficiency, it is measured on a scale of 0-30 with higher point attainment signalling worse outcome

  6 months to 9 months

• Difference in self-sufficiency self-reported in Questionnaire of functional state (abbreviation in original language: subjective FAQ-CZ) at 3 months between the Probiotics C2P/Placebo and Placebo/C2P Probiotics group

  FAQ-CZ is a self-report measure of self-sufficiency, it is measured on a scale of 0-30 with higher point attainment signalling worse outcome

  3 months

• Difference in self-sufficiency self-reported in Questionnaire of functional state (abbreviation in original language: subjective FAQ-CZ) at 6 months between the Probiotics C2P/Placebo and Placebo/C2P Probiotics group

  FAQ-CZ is a self-report measure of self-sufficiency, it is measured on a scale of 0-30 with higher point attainment signalling worse outcome

  6 months

• Changes in tau protein

  Measured in pg/ml; 2x10ml samples collected to assess tau protein, neurofilament light and immunocomplex antibody levels

  baseline to 3 months

• Changes in tau protein

  Measured in pg/ml; 2x10ml samples collected to assess tau protein, neurofilament light and immunocomplex antibody levels

  baseline to 6 months

• Changes in tau protein

  Measured in pg/ml; 2x10ml samples collected to assess tau protein, neurofilament light and immunocomplex antibody levels

  3 months to 6 months

• Changes in tau protein

  Measured in pg/ml; 2x10ml samples collected to assess tau protein, neurofilament light and immunocomplex antibody levels

  6 months to 9 months

• Changes in neurofilament light levels

  Measured in pg/ml; 2x10ml samples collected to assess tau protein, neurofilament light and immunocomplex antibody levels

  baseline to 3 months

• Changes in neurofilament light levels

  Measured in pg/ml; 2x10ml samples collected to assess tau protein, neurofilament light and immunocomplex antibody levels

  baseline to 6 months

• Changes in neurofilament light levels

  Measured in pg/ml; 2x10ml samples collected to assess tau protein, neurofilament light and immunocomplex antibody levels

  3 months to 6 months

• Changes in neurofilament light levels

  Measured in pg/ml; 2x10ml samples collected to assess tau protein, neurofilament light and immunocomplex antibody levels

  6 months to 9 months

• Changes in immunocomplex antibody levels

  Measured in ng/ml; 2x10ml samples collected to assess tau protein, neurofilament light and immunocomplex antibody levels

  baseline to 3 months

• Changes in immunocomplex antibody levels

  Measured in ng/ml; 2x10ml samples collected to assess tau protein, neurofilament light and immunocomplex antibody levels

  baseline to 6 months

• Changes in immunocomplex antibody levels

  Measured in ng/ml; 2x10ml samples collected to assess tau protein, neurofilament light and immunocomplex antibody levels

  3 months to 6 months

• Changes in immunocomplex antibody levels

  Measured in ng/ml; 2x10ml samples collected to assess tau protein, neurofilament light and immunocomplex antibody levels

  6 months to 9 months

• Biochemical parameters in blood

  Change from baseline Blood metabolome assessed using mass spectrometry at 3 months

  baseline to 3 months

• Biochemical parameters in blood

  Change from baseline Blood metabolome assessed using mass spectrometry at 6 months

  baseline to 6 months

• Biochemical parameters in blood

  Change from 3 months Blood metabolome assessed using mass spectrometry at 6 months

  3 months to 6 months

• Biochemical parameters in blood

  Change from 3 months Blood metabolome assessed using mass spectrometry at 6 months

  6 months to 9 months

• Biochemical parameters in urine

  15ml sample collected twice at each visitation time point (at home in the morning, during centre visit); Change from baseline Urine metabolome assessed using mass spectrometry at 3 months

  baseline to 3 months

• Biochemical parameters in urine

  15ml sample collected twice at each visitation time point (at home in the morning, during centre visit); Change from baseline Urine metabolome assessed using mass spectrometry at 6 months

  baseline to 6 months

• Biochemical parameters in urine

  15ml sample collected twice at each visitation time point (at home in the morning, during centre visit); Change from 3 months Urine metabolome assessed using mass spectrometry at 6 months

  3 months to 6 months

• Biochemical parameters in urine

  15ml sample collected twice at each visitation time point (at home in the morning, during centre visit); Change from 3 months Urine metabolome assessed using mass spectrometry at 6 months

  6 months to 9 months

• Biochemical parameters in stool

  Change from baseline Stool metabolome assessed using mass spectrometry at 3 months

  baseline to 3 months

• Biochemical parameters in stool

  Change from baseline Stool metabolome assessed using mass spectrometry at 6 months

  baseline to 6 months

• Biochemical parameters in stool

  Change from 3 months Stool metabolome assessed using mass spectrometry at 6 months

  3 months to 6 months

• Biochemical parameters in stool

  Change from 3 months Stool metabolome assessed using mass spectrometry at 6 months

  6 months to 9 months

Secondary Outcomes (84)

• Change from baseline Questionnaire of adverse events (abbreviation in original language: DNU) at 3 months

  baseline to 3 months

• Change from baseline Questionnaire of adverse events (abbreviation in original language: DNU) at 6 months

  baseline to 6 months

• Change from 3 months Questionnaire of adverse events (abbreviation in original language: DNU) at 6 months

  3 months to 6 months

• Change from 6 months Questionnaire of adverse events (abbreviation in original language: DNU) at 9 months

  6 months to 9 months

• Difference in the Questionnaire of adverse events (abbreviation in original language: DNU) at 3 months between the Probiotics C2P/Placebo and Placebo/C2P Probiotics group

  3 months

Study Arms (2)

Probiotics C2P/Placebo

EXPERIMENTAL

Crossover design does not confine one group of patients strictly either to an intervention in question or a placebo. Each group will receive both placebo and probiotics in tandem, but in a reversed order.

Dietary Supplement: Probiotics C2P

Placebo/Probiotics C2P

EXPERIMENTAL

Crossover design does not confine one group of patients strictly either to an intervention in question or a placebo. Each group will receive both placebo and probiotics in tandem, but in a reversed order.

Dietary Supplement: Probiotics C2P

Interventions

Probiotics C2P DIETARY_SUPPLEMENT

Probiotics will supplement normal diet. Unlike other products available on the market, which are usually of bovine origin, our probiotic has been manufactured using human-stemmed lines. The supplements are composed of a mixture of naturally occurring human gut bacteria.

Placebo/Probiotics C2P; Probiotics C2P/Placebo

Eligibility Criteria

• Age: 55 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• is 55-80 years of age
• His/her native language is Czech
• Is willing to visit the testing centre four times within half a year
• Is willing to provide blood, urine and stool samples three times within half a year
• Is willing to self-administer the probiotic/placebo pill once every day for half a year
• is self-sufficient (handling finances, travelling without a chaperone, administration of medication, correct phone usage, filling forms, meal preparation)
• Has good vision; Can read and write, glasses are acceptable
• Has good hearing to hear and understand all instructions during examination
• Can walk well (walking aids are acceptable) to attend all the examinations

You may not qualify if:

• Suffers with disorder(s) of digestive system, primarily gastrointestinal disorders (celiac disease, ulcerative colitis, Crohn's disease, frequent diarrhoea)
• Had severe neurological difficulties (epilepsy, stroke, severe head trauma, meningitis in the past 10 years, brain surgery, brain tumour, prolonged period(s) in an unconscious state - excluding general anaesthesia)
• Had been treated/Is currently being treated for the following psychiatric disorders: alcohol/medication/drug of abuse dependance, schizophrenia, psychotic disorder, bipolar disorder
• Is taking medication for depression or low mood
• Suffers from internal organ failure (heart, liver or kidney failure etc.)
• Suffered from an oncological problem (cancer) in the past 5 years
• Underwent radiotherapy or chemotherapy in the past
• Underwent a surgery/procedure under general anaesthesia in the past three years or has a planned procedure/surgery under general anaesthesia in the next 6 months over the course of this trial
• Suffered from hepatitis (hepatitis B, C), HIV or syphilis in the past
• Had taken any probiotics in the past three months

Sponsors & Collaborators

• National Institute of Mental Health, Czech Republic: lead
• C2P s.r.o.: collaborator
• University Hospital Vinohrady: collaborator
• Ministry of Industry and Trade, Czech Republic: collaborator

Study Sites (2)

University Hospital Vinohrady

Prague, 10034, Czechia

Location

National Institute of Mental Health, Czech Republic

Prague, 25067, Czechia

Location

Related Publications (2)

• Bartos A, Weinerova J, Diondet S. Effects of human probiotics on memory and psychological and physical measures in community-dwelling older adults with normal and mildly impaired cognition: results of a bi-center, double-blind, randomized, and placebo-controlled clinical trial (CleverAge biota). Front Aging Neurosci. 2023 Jul 7;15:1163727. doi: 10.3389/fnagi.2023.1163727. eCollection 2023.

  PMID: 37502424 DERIVED

• Bartos A, Weinerova J, Diondet S, Vales K. Effect of human probiotics on memory, psychological and biological measures in elderly: A study protocol of bi-center, double-blind, randomized, placebo-controlled clinical trial (CleverAge Biota). Front Aging Neurosci. 2022 Nov 10;14:996234. doi: 10.3389/fnagi.2022.996234. eCollection 2022.

  PMID: 36437993 DERIVED

Related Links

• National Institute of Mental Health - official website

MeSH Terms

Conditions

Memory Disorders; Cognitive Dysfunction

Condition Hierarchy (Ancestors)

Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Cognition Disorders; Neurocognitive Disorders; Mental Disorders

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Participants with an odd identification number will receive substance A in the first three months and a complementary substance B in the following three months. Participants with an even identification number will receive substance B in the first three months and a complementary substance A in the following three months. Manufacturer of the new probiotics C2P will mark one set of substances as set A and a complementary set of substances as set B. If substance A/B is a probiotic or placebo will be known to a manufacturer only. Investigators and participants are blinded to this information.
• Purpose: SUPPORTIVE CARE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: First 3 months: group A on probiotics; group B on placebo Next 3 months: group A on placebo; group B on probiotics. Next 3 months: no intervention in either group

Study Record Dates

• First Submitted: April 28, 2021
• First Posted: September 21, 2021
• Study Start: January 6, 2021
• Primary Completion: March 2, 2022
• Study Completion: March 2, 2022
• Last Updated: June 1, 2023

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will share

Locations

CZ (2)