Prebiotic Supplementation and Intestinal Barrier Function in Elderly: a RCT

Study Overview
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Brief Summary
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The investigators aim was to assess whether 6 weeks of oral intake of the wheat-derived prebiotic fiber arabinoxylan or oat-derived beta-glucan could improve intestinal barrier function against drug-induced barrier disruption in a general population of elderly people, in a randomized double blinded placebo-controlled clinical trial.

Detailed Description
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The study consisted of a 9 week clinical trial to which the study participants orally ingested two different prebiotic compounds/one placebo for a total of 6 weeks. The primary outcome was intestinal permeability which was measured before/after indomethacin intake before starting with the prebiotic supplementation and repeated 6 weeks afterwards. Indomethacin is an NSAID known to artificially increase the intestinal permeability. The prebiotic fibers arabinoxylan and oat-derived beta-glucan have not been investigated for their effect on intestinal permeability in older adults. Intestinal permeability was investigated using the multi-sugar permeability test. Participants ingested a water solution containing 5 sugar probes that are taken up in different parts of the gut. These sugars are later recovered in the urine at two different time points, reflecting gastroduodenal, small intestinal and colonic permeability.

Official Title
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The Influence of Prebiotic Supplementation on Intestinal Barrier Function in Elderly: A Randomized Placebo Controlled Clinical Trial

Conditions
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Prebiotics, Aged

Intervention / Treatment
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* Dietary Supplement: Naxus
* Dietary Supplement: Oatwell
* Dietary Supplement: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Informed consent signed by study participant Age ≥ 55 years Mentally and physically fit to complete questionnaires during the study period Exclusion Criteria: Known or genic gastrointestinal disease, with strictures, malignance's and ischemia. Inflammatory bowel diseases (IBD) Participation in other clinical trials in the past three months. Intake of medications know to change the inflammatory status (i.e proton pump inhibitors, antibiotic, anti-inflammatory medication (including NSAIDs)

Ages Eligible for Study
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Minimum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: The study participants were allocated through block randomization into three different intervention arms that ran in parallell throughout the study
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Maltodextrin 12 gram used as placebo | Dietary Supplement: Placebo<br>* Maltodextrin as placebo<br>|
| Active Comparator: Naxus<br>Naxus contains the wheat-derived prebiotic fibre Arabinoxylan | Dietary Supplement: Naxus<br>* Non-digestible polysaccharides arabinoxylan (Naxus)<br>* Other names: Placebo;|
| Active Comparator: Oatwell<br>Oatwell contains an oat-derived prebiotic beta-glucan fibre | Dietary Supplement: Oatwell<br>* Non-digestible polysaccharides oat beta-glucan (Oatwell)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in delta indomethacin challenged permeability at end of intervention period | In vivo multi-sugar permeability test | 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in faecal microbiota composition at end of intervention period | 16S rRNA-based sequencing | 6 weeks | 
| Changes in cytokine levels at end of intervention period | Multiplex assay for IL-1β, IL-6, IL-8, IL-10, IL-2, IL-12p70, IFN-γ and TNF-α | 6 weeks | 
| Changes in reactive oxygen species levels at end of intervention period | FORT test for hydrogen peroxide | 6 weeks | 
| Changes in gastrointestinal symptom questionnaire scores at end of intervention period | The Gastrointestinal Symptoms Rating Scale (GSRS) evaluates gastrointestinal (GI) symptoms based on the 5 domains diarrhoea, constipation, reflux, indigestion and abdominal pain. The symptoms are assessed with 15 items, ranging in scores 1 to 7 depending on their severity. A score of 1 represents no problems and score 7 represents severe problems. The severity of symptoms may be defined as no problems (1 point), mild (1-2 points), moderate (2-4 points), and severe (4-7 points). The scores for each domain was calculated as the mean score of each corresponding item while the mean total GSRS score reflects the general severity of GI symptoms. | 6 weeks | 
| Changes in hospital and anxiety depression scores at end of intervention period | The Hospital Anxiety and Depression Scale (HADS) was used to evaluate the psychological distress of study participants.This questionnaire consists of 14 items subdivided in two subscales for the assessment of anxiety or depression. The total score is used as a measure of general psychological distress. The minimum score is 0 and the maximum score is 21. A score > 8 on respective subscales indicates a significant level of anxiety or depression. | 6 weeks | 
| Changes in perceived stress scale scores at end of intervention period | The perceived stress scale (PSS) consists of 10 items, including a number of direct questions about current levels of experienced stress. The respondent answers how often a certain emotion has been present during the past month. PSS scores are obtained by reversing responses (e.g., 0 = 4, 1 = 3, 2 = 2, 3 = 1 & 4 = 0) to the four positively stated items (items 4, 5, 7, & 8) and then summing across all scale items. Each item is rated on a 5-point scale ranging from never (0) to almost always (4). The questions in this scale ask about the responders feelings and thoughts during the last month. In each case the questionnaire requires the respondent to indicate by circling how often they felt or thought a certain way. | 6 weeks | 
| Changes in quality of life questionnaire scores at end of intervention period | The EuroQol 5D-5L (EQ-5D-5L) tool consists of two parts; 5Q-5D, which includes 5 items related to wellbeing and function (mobility, self-care, usual activities, pain/discomfort and anxiety/ depression) and the visual analogue scale, 5Q-5D-VAS, ranging from 0 to 100. | 6 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Older adults, Prebiotics, Intestinal permeability, NSAIDS