Synbiotic Approach to Immunity and Metabolism in the Elderly Study

Study Overview
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Brief Summary
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The aging process leads to a marked decline in immune function (immunosenescence), causing a significant reduction in immune response after vaccination or infections. Dietary intervention is an attractive, safe and non-invasive way to impact on gut bacteria and subsequently the functioning of the immune system. The ability of the dietary supplementation to alter these functions can be of particular importance in those groups that have an underdeveloped, poorly functioning immune system such as infants, immuno-compromised subjects or elderly. Research over the past two decades has provided evidence that administration of probiotics (live microorganisms which, when administered in adequate amounts, confer a health benefit on the host) could enhance immune function. Lactobacilli and bifidobacteria are the most common probiotics used in humans and various strains have been shown to have immunostimulatory properties in vitro and in experimental models, these properties include modulation of cytokine production. evidence exists of the immunostimulating effects of certain probiotics and the potential to use prebiotics to increase the levels of beneficial bacteria (which are known to be reduced in elderly population). Furthermore, by providing a probiotic at the same time as a prebiotic conditions for survival are enhanced. To date, only a small number of studies conducted have been randomised and/or placebo controlled to unequivocally demonstrate efficacies.

Detailed Description
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The aim of this study is to investigate the effect of probiotic Lactobacillus rhamnosus GG (commercialised as LGG), a pilus-less derivative L. rhamnosus GG (LGG-PB12)combined with a putative prebiotic PromitorTM (soluble corn fiber) i.e. a synbiotics and PromitorTM (SCF alone) on the faecal microbiota composition, metabolism and immunity in healthy individuals aged 60-80 years. It consists of a 3 week randomised intervention treatment periods with the synbiotics, prebiotic and placebo control. Any adverse medical events which occur during the trial (e.g. headache, gut symptoms) should be recorded in a diary along with medication taken.

Official Title
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Randomised, Double-blind, Placebo Controlled Cross-over Study to Determine the Beneficial Effects of Synbiotics and PromitorTM (Soluble Corn Flour)on Metabolism and Immunity in Healthy 60-80 Years Old Individuals

Conditions
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Healthy

Intervention / Treatment
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* Dietary Supplement: LGG+Promitor™
* Dietary Supplement: Promitor™
* Dietary Supplement: LGG-PB12+Promitor™
* Dietary Supplement: Maltodextrin


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: aged between 60 and 80 years of age. in good general health, defined as no comorbidities requiring regular medical follow up Ability to communicate well with the investigator and to comply with the requirements of the entire study Exclusion criteria: History or evidence of organic disease of the gastrointestinal tract; such as tumour, irritable bowel syndrome, etc., within the previous 5 years Consumed probiotic or prebiotic preparations on a regular basis (at least 3 times per week) in the last 2 weeks and during the trial period Former participation in another study involving prebiotic or probiotic preparations or investigational drugs within the previous 6 months, or intention to use such drugs during the course of the study Undergone surgical resection of any part of the bowel History of malignancy within the previous 5 years (with exception of well-treated basal cell carcinoma or in situ cervical carcinoma). Currently prescribed immunosuppressive drugs Intention to use regularly other medication which affects gastrointestinal motility and/or perception Current or recent history (within 12 months) of significant drug or alcohol abuse or dependence

Ages Eligible for Study
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Minimum Age: 60 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Crossover assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LGG+Promitor™<br>LGG:10^12 CFU/g Lactobacillus rhamnosus GG (commercialised as LGG) combined with Promitor™:12g fibres/delivered of Soluble Corn Fibre (SCF) as dry powders to be consumed as 250 ml beverages at breakfast. | Dietary Supplement: LGG+Promitor™<br>* synbiotic<br>|
| Experimental: Promitor™<br>Promitor™:12g fibres/delivered of Soluble Corn Fibre (SCF) as dry powders to be consumed as 250 ml beverages at breakfast. | Dietary Supplement: Promitor™<br>* Soluble Corn Fiber<br>|
| Experimental: LGG-PB12+Promitor™<br>LGG-PB12:10^12 CFU/g of a pilus-less derivative L. rhamnosus GG combined with Promitor™:12g fibres/delivered of Soluble Corn Fibre (SCF) as dry powders to be consumed as 250 ml beverages at breakfast. | Dietary Supplement: LGG-PB12+Promitor™<br>* synbiotic<br>|
| Placebo Comparator: Maltodextrin<br>Maltodextrin (an oligosaccharide without prebiotic effect) 12g delivered and served as dry powders to be consumed as 250 ml beverages at breakfast. | Dietary Supplement: Maltodextrin<br>* Control<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The modulation of the gut microbiota by synbiotics and PromitorTM inflammatory/immune biomarkers | Fecal16S rRNA amplicon sequencing to assess changes in fecal bacterial abundance and species diversity | Changes from baseline to 21 days synbiotics and PromitorTM treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The modulation of immune function by synbiotics and PromitorTM | Blood samples analysis to assess changes in cytokines production | Changes from baseline to 21 days synbiotics and PromitorTM treatment |