Clinical trial NCT05892627: A Supplement on Cognitive Function and Brain Activity in Middle Age and Older Healthy Adults
Official title: PoZibio a Post-biotic Supplement on Cognitive Function and Brain Activity in Middle Age and Older Healthy Adults
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: EARLY_PHASE1
Conditions: Cognitive Decline
Keywords: Electroencephalography
Post-biotic
Lactobacillus paracasei
Cognitive health
Mental function
Metabolomics
Lead sponsor: Aberystwyth University
Sponsor class: OTHER
Collaborators: name: AGROCEUTICAL PRODUCTS LTD
name: Neurodyn Life Sciences Inc.
name: Postbiotics Inc
name: Welsh Government
First posted: 2023-06-07
Enrollment: 40
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: A cohort who will be randomised into PoZibio™ (2 x capsules daily) or placebo (2 x capsules daily) supplementation for 6 weeks.
Primary purpose: SUPPORTIVE_CARE

Brief summary: PoZibio™ capsules contains Lactobacillus paracasei which has been heat-killed (post-biotic).

The researchers will recruit a cohort of middle aged and older adults (\>50 years) who will be randomised into PoZibio™ (2 x capsules daily) or placebo (2 x capsules daily) supplementation for 6 weeks. Subjects will be asked to take both capsules in the morning with their breakfast. The placebo will be matched to the active product by taste and texture.

Electroencephalography (EEG) shall be combined with 3 psychological tasks, to measure a variety of cognitive domains including attention, processing speed, accuracy, and response inhibition. These psychological tasks shall include the Stroop task, the Go/No-go task, and the Flanker task. Before taking part in the psychological tasks, participants shall be required to have their EEG resting state recorded, requiring them to participate in an Eyes Open/Closed Task.

The Mini Mental State Exam (MMSE) questionnaire shall be used as a digital screening tool to assess global cognitive function in participants both prior to and following the 6-week PoZibio trial. The geriatric depression scale (GDS) shall also be used as a digital screening tool to assess for depressive symptomatology in older adults. The EQ-5D questionnaire shall be used to obtain an overall profile of the health state and quality of life of participants before and after the trial.

The researchers will collect venous blood samples for the investigation into the chemical composition using metabolomics, the quantification of short chain fatty acids as well as clinical biochemistry, before and after the trial.

Aim:

A randomised, placebo controlled parallel human clinical trial of heat-treated Lactobacillus paracasei (post-biotics) in healthy middle aged and older subjects is proposed, to assess the potential for clinically relevant benefits in terms of cognitive function.

Detailed description: Nowadays, the oral use of probiotics is widespread, in foods (i.e., yogurt), drinks (i.e., kombucha) and supplements. Heat-treated probiotics (essentially pasteurised or killed), cell-free supernatants, and purified key components can confer beneficial effects, mainly immune effects, protection against bacterial infections, and maintenance of gut health, which can positively impact on mental health and cognitive ability. Postbiotics, as they are called, have an advantage for food industry applications as they can easily be supplemented in several food lines/products and are shelf stable. PoZibio™ capsules contains the probiotics Lactobacillus paracasei which is a species of lactic acid bacteria often used in the fermentation of dairy products. It's found in the human intestinal tract and mouth, but also in foods such as yogurt and naturally fermented vegetables and milk. This has been heat-killed in PoZibio™(post biotic).

The researchers are aiming to recruit a cohort of middle aged and older adults (\>50 years) who will be randomised into PoZibio™ (2 x capsules daily) or placebo (2 x capsules daily) supplementation for 6 weeks. Subjects will be asked to take both capsules in the morning with their breakfast. The placebo will be matched to the active product by taste and texture.

Electroencephalography (EEG) shall be combined with 3 psychological tasks in a computer program called E-Prime, to measure a variety of cognitive domains including attention, processing speed, accuracy, and response inhibition. These psychological tasks shall include the Stroop task, the Go/No-go task, and the Flanker task. Before taking part in the psychological tasks, participants shall be required to have their EEG resting state recorded, requiring them to participate in an Eyes Open/Closed Task.

The Mini Mental State Exam (MMSE) questionnaire shall be used as a digital screening tool to assess global cognitive function in participants both prior to and following the 6-week PoZibio™ trial. The geriatric depression scale (GDS) shall also be used as a digital screening tool to assess for depressive symptomatology in older adults. The EQ-5D questionnaire shall be used to obtain an overall profile of the health state and quality of life of participants, before and after the trial.

The researchers will collect venous blood samples for the investigation into the chemical composition using metabolomics, the quantification of short chain fatty acids as well as clinical biochemistry, before and after the trial.

Aim:

A randomised, placebo controlled parallel human clinical trial of heat-treated Lactobacillus paracasei (post-biotics) in healthy middle aged and older subjects is proposed, to assess the potential for clinically relevant benefits in terms of cognitive function.

Eligibility criteria: Inclusion Criteria:

* Subjects over 50 years of age
* Subjects with Mini-Mental State Exam (MMSE) of 25-30 inclusive (global cognitive function)
* Subjects who are able to undergo EEG and to commit to visits to WARU/P5.
* Subjects who are able to provide venous blood samples.
* Subjects able to provide written informed consent PRIOR to performing any study procedures.

Exclusion Criteria:

* Subjects with diagnosis of Alzheimer's disease or other dementia
* Subjects taking medication for the treatment of dementia (such as acetylcholinesterase inhibitors (Aricept, Excelon), memantine (Namenda) or other medications with similar mechanisms of action) or medical foods (such as Cerefolin, Souvenaid, Axona) for the treatment of dementia.
* Subjects who are already regularly taking probiotics, post-biotics, nutraceutical and/or vitamin supplements related to PoZibio ™ within 30 days of screening.
* Subjects with Geriatric Depression Scale \> 6
* Subjects with a Mini Mental State Exam score below 25
* Subjects who are pregnant or lactating
* Subjects with medical condition or disease that is life threatening
* Subjects who smoke cigarettes or use other products containing nicotine.
* Subjects diagnosed with diabetes.
* Subjects taking warfarin.
* Subjects who identify as being vegetarian or vegan
* Subjects who have a diagnosed or suspected mental health condition, or who have any concerns surrounding their mental health
* Subjects who have immediate family members with diagnosed mental health condition or suspected mental health concerns

Primary outcomes:
measure: Cognitive Control (Selective attention, processing speed, mental flexibility)
timeFrame: Improved score (faster response time and improved accuracy) from baseline score at 6 weeks after pozibio
measure: Cognitive Control (Selective attention, processing speed, mental flexibility)
timeFrame: Improved score (faster response time and improved accuracy) at 6 weeks after pozibio when compared with placebo after 6 weeks
measure: Response inhibition (core construct in cognitive control and self-regulation)
timeFrame: Improved (fewer commission errors) score from baseline score at 6 weeks after pozibio
measure: Response inhibition (core construct in cognitive control and self-regulation)
timeFrame: Improved (fewer commission errors ) score at 6 weeks after pozibio when compared with placebo after 6 weeks
measure: Selective attention and response inhibition (core constructs in cognitive control and self-regulation)
timeFrame: Improved score (faster response time and improved accuracy) from baseline score at 6 weeks after pozibio
measure: Selective attention and response inhibition (core constructs in cognitive control and self-regulation)
timeFrame: Improved score (faster response time and improved accuracy) at 6 weeks after pozibio when compared with placebo after 6 weeks
measure: Electroencephalogram (EEG) during the Stroop task
timeFrame: After 6 weeks of pozibio, no delay of the P3 component and more N2 components when compared with baseline
measure: Electroencephalogram (EEG) during the Stroop task
timeFrame: After 6 weeks of pozibio, no delay of the P3 component and more N2 components when compared with 6 weeks of placebo
measure: Electroencephalogram (EEG) during the Flanker task
timeFrame: After 6 weeks of pozibio, no delay of the P3 component and more N2 components when compared with baseline
measure: Electroencephalogram (EEG) during the Flanker task
timeFrame: After 6 weeks of pozibio, no delay of the P3 component and more N2 components when compared with 6 weeks of placebo
measure: Electroencephalogram (EEG) during the go/no-go task
timeFrame: After 6 weeks of pozibio, no delay of the P3 component and more N2 components when compared with baseline
measure: Electroencephalogram (EEG) during the go/no-go task
timeFrame: After 6 weeks of pozibio, no delay of the P3 component and more N2 components when compared with 6 weeks of placebo
measure: Electroencephalogram (EEG) during the stroop task
timeFrame: After 6 weeks of pozibio, increased alpha and delta activity when compared with baseline
measure: Electroencephalogram (EEG) during the Flanker task
timeFrame: After 6 weeks of pozibio, increased alpha and delta activity when compared with baseline
measure: Electroencephalogram (EEG) during the go/no-go task
timeFrame: After 6 weeks of pozibio, increased alpha and delta activity when compared with baseline
measure: Electroencephalogram (EEG) during the stroop task
timeFrame: After 6 weeks of pozibio, increased alpha and delta activity when compared with 6 weeks of placebo
measure: Electroencephalogram (EEG) during the Flanker task
timeFrame: After 6 weeks of pozibio, increased alpha and delta activity when compared with 6 weeks of placebo
measure: Electroencephalogram (EEG) during the go/no-go task
timeFrame: After 6 weeks of pozibio, increased alpha and delta activity when compared with 6 weeks of placebo
measure: EuroQol 5 Dimension 5L (combined score)
timeFrame: Reduced score from baseline EuroQol 5 Dimension 5 score at 6 weeks after pozibio
measure: EuroQol 5 Dimension 5L (combined score)
timeFrame: Reduced EuroQol 5 Dimension 5 score at 6 weeks after pozibio when compared with placebo after 6 weeks
Secondary outcomes:
measure: Changes in short chain fatty acids concentrations in plasma
timeFrame: Increased concentration of total short chain fatty acids after the pozibio at 6 weeks compared with the baseline
measure: Changes in short chain fatty acids concentrations in plasma
timeFrame: Increased concentration of total short chain fatty acids after the pozibio at 6 weeks compared with that after placebo at 6 weeks
Other outcomes:
Locations:
city: Aberystwyth
country: United Kingdom
facility: Well-being and Health Assessment Research Unit (WARU)
state: Ceredigion
Study officials:
affiliation: Aberystwyth University
name: Amanda J Lloyd, PhD, BSc
role: PRINCIPAL_INVESTIGATOR
References: