Effects of β-glucans on Gut Permeability and Microbiota in Elderly

Sponsor

Örebro University, Sweden (Other)

Overall Status

Completed

CT.gov ID

NCT05584254

Collaborator

KERRY GROUP P.L.C. (Other)

Enrollment

Location

Arms

28.5

Actual Duration (Months)

1.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The investigators aim was to compare healthy young adults, senior orienteers (model of healthy ageing) and elderly with gastrointestinal symptoms on intestinal permeability, microbiota compositions and well-being. In addition, assess whether 3 weeks of oral intake of soluble or dispersible forms yeast-dervied beta-glucan could improve intestinal barrier function against drug-induced barrier disruption vs placebo for a cohort of elderly people with gastrointestinal symptoms, in a randomized double blinded placebo-controlled cross-over clinical trial.

Condition or Disease	Intervention/Treatment	Phase
Elderly Bowel Symptoms Prebiotics	Dietary Supplement: yeast-beta glucan	N/A

Detailed Description

Baseline samples for measurements of intestinal permeability (multisugar test), microbiota composition (faecal samples) and well-being (questionnaires) were collected during the first week for:

Young healthy adults (healthy young controls) Senior orienteers (healthy elderly controls) Elderly with gastrointestinal (GI) symptoms

Thereafter only the elderly with GI symptoms continued into the randomized cross-over trial where they were blindly and randomly distributed one of the following: Soluble yeast-derived beta-glucan, dispersible (whole) yeast-derived beta-glucan and placebo. Each supplement was taken for 3 weeks with a 1 week washout until all participants had taken all supplements. Towards the end of each supplement period, samples for measurement of intestinal permeability and microbiota were collected, in addition to questionnaires being filled out.

Study Design

Study Type:

Interventional

Actual Enrollment :

43 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Intervention Model Description:

3 study products (2 different forms of yeast-beta glucan and a placebo) taken in a cross-over design.3 study products (2 different forms of yeast-beta glucan and a placebo) taken in a cross-over design.

Masking:

Triple (Participant, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

Effects of β-glucan Based Dietary Fibres on Indomethacin-induced Hyperpermeability and Gut Microbiota Composition in Elderly: A Randomized Placebo-controlled Crossover Clinical Trial

Actual Study Start Date :

Apr 1, 2015

Actual Primary Completion Date :

Aug 14, 2017

Actual Study Completion Date :

Aug 14, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Elderly with gastrointestinal symptoms The target group for the intervention and cohort of interest used for comparison of baseline characteristics between control groups. Went into a cross-over design with 2 yeast-derived beta-glucan supplements and a placebo.	Dietary Supplement: yeast-beta glucan
No Intervention: Senior orienteers A model of healthy aged elderly used as a control group for the baseline characteristics.
No Intervention: Young healthy adults A cohort of young healthy adults used as a control group for the baseline characteristics.

Arm

Intervention/Treatment

Experimental: Elderly with gastrointestinal symptoms

The target group for the intervention and cohort of interest used for comparison of baseline characteristics between control groups. Went into a cross-over design with 2 yeast-derived beta-glucan supplements and a placebo.

Dietary Supplement: yeast-beta glucan

No Intervention: Senior orienteers

A model of healthy aged elderly used as a control group for the baseline characteristics.

No Intervention: Young healthy adults

A cohort of young healthy adults used as a control group for the baseline characteristics.

Outcome Measures

Primary Outcome Measures

Intestinal permeability at baseline (before indomethacin) [Day 1]
In vivo gastrointestinal permeability measured by oral intake of multi-sugar test before intake of indomethacin. Urine collected over 24 hours for measurement of excreted sugars.
Intestinal permeability at baseline (after indomethacin) [Day 1]
In vivo gastrointestinal (GI) permeability measured by oral intake of multi-sugar test after intake of indomethacin (GI barrier disruption challenge). Urine collected over 24 hours for measurement of excreted sugars.
Changes in Intestinal permeability 3 weeks after study supplementation 1 (before indomethacin). [3 weeks]
Performed after study participants have orally taken study supplementation 1 for 3 weeks. In vivo gastrointestinal permeability measured by oral intake of multi-sugar test before intake of indomethacin. Urine collected over 24 hours for measurement of excreted sugars.
Changes in intestinal permeability 3 weeks after study supplementation 1 (after indomethacin). [3 weeks]
Performed after study participants have orally taken study supplementation 1 for 3 weeks. In vivo gastrointestinal (GI) permeability measured by oral intake of multi-sugar test after intake of indomethacin (GI barrier disruption challenge). Urine collected over 24 hours for measurement of excreted sugars.
Changes in intestinal permeability 3 weeks after study supplementation 2 (before indomethacin) [3 weeks]
Performed after study participants have orally taken study supplementation 2 for 3 weeks. In vivo gastrointestinal permeability measured by oral intake of multi-sugar test before intake of indomethacin. Urine collected over 24 hours for measurement of excreted sugars.
Changes in intestinal permeability 3 weeks after study supplementation 2 (after indomethacin) [3 weeks]
Performed after study participants have orally taken study supplementation 2 for 3 weeks. In vivo gastrointestinal (GI) permeability measured by oral intake of multi-sugar test after intake of indomethacin (GI barrier disruption challenge). Urine collected over 24 hours for measurement of excreted sugars.
Changes in intestinal permeability 3 weeks after study supplementation 3 (before indomethacin) [3 weeks]
Performed after study participants have orally taken study supplementation 3 for 3 weeks. In vivo gastrointestinal permeability measured by oral intake of multi-sugar test before intake of indomethacin. Urine collected over 24 hours for measurement of excreted sugars.
Changes in intestinal permeability 3 weeks after study supplementation 3 (after indomethacin) [3 weeks]
Performed after study participants have orally taken study supplementation 3 for 3 weeks. In vivo gastrointestinal (GI) permeability measured by oral intake of multi-sugar test after intake of indomethacin (GI barrier disruption challenge). Urine collected over 24 hours for measurement of excreted sugars.

Secondary Outcome Measures

Microbiota diversity - at baseline [Day 1]
Faecal samples will be used for next-generation sequencing and analysed for diversity
Bacterial species - at baseline [Day 1]
Faecal samples will be used for next-generation sequencing and analysed for bacterial species
Changes in microbiota diversity 3 weeks after study supplementation 1 [3 weeks]
Faecal samples will be used for next-generation sequencing and analysed for changes in microbiota diversity
Changes in bacterial species 3 weeks after study supplementation 1 [3 weeks]
Faecal samples will be used for next-generation sequencing and analysed for changes in bacterial species levels
Changes in microbiota diversity 3 weeks after study supplementation 2 [3 weeks]
Faecal samples will be used for next-generation sequencing and analysed for changes in microbiota diversity
Changes in bacterial species 3 weeks after study supplementation 2 [3 weeks]
Faecal samples will be used for next-generation sequencing and analysed for changes in bacterial species levels
Changes in microbiota diversity 3 weeks after study supplementation 3 [3 weeks]
Faecal samples will be used for next-generation sequencing and analysed for changes in microbiota diversity
Changes in bacterial species 3 weeks after study supplementation 3 [3 weeks]
Faecal samples will be used for next-generation sequencing and analysed for changes in bacterial species levels
Changes in microbiota diversity - Washout (1 week after ending supplementation 1, i.e. 4 weeks after baseline) [4 weeks]
Faecal samples will be used for next-generation sequencing and analysed for changes in microbiota diversity from 1 weeks washout, after ending study supplementation 1 (4 weeks after baseline)
Changes in bacterial species - Washout (1 week after ending study supplementation 1, i.e. 4 weeks after baseline) [4 weeks]
Faecal samples will be used for next-generation sequencing and analysed for changes in bacterial species from 1 weeks washout, after ending study supplementation 1 (4 weeks after baseline)
Changes in microbiota diversity - Washout (1 week after ending study supplementation 2, i.e. 4 weeks after baseline) [4 weeks]
Faecal samples will be used for next-generation sequencing and analysed for changes in microbiota diversity from 1 weeks washout, after ending study supplementation 2 (4 weeks after baseline)
Changes in bacterial species - Washout (1 week after ending study supplementation 2, i.e. 4 weeks after baseline) [4 weeks]
Faecal samples will be used for next-generation sequencing and analysed for changes in bacterial species from 1 weeks washout, after ending study supplementation 2 (4 weeks after baseline).
Changes in microbiota diversity - Washout (1 week after ending study supplementation 3, i.e. 4 weeks after baseline) [4 weeks]
Faecal samples will be used for next-generation sequencing and analysed for changes in microbiota diversity from 1 weeks washout, after ending study supplementation 3 (4 weeks after baseline)
Changes in bacterial species - Washout (1 week after ending study supplementation 3, i.e. 4 weeks after baseline) [4 weeks]
Faecal samples will be used for next-generation sequencing and analysed for changes in bacterial species from 1 weeks washout, after ending study supplementation 3 (4 weeks after baseline)
Changes in gastrointestinal symptom questionnaire scores [up to 13 weeks]
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.
Changes in hospital and anxiety depression scores [up to 13 weeks]
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.
Changes in perceived stress scale scores [Up to 13 weeks]
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.
Changes in quality of life questionnaire scores [Up to 13 weeks]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

55 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Elderly with gastrointestinal symptoms

Inclusion Criteria:

Informed consent signed by study participant
Age >55 years
Scoring above 2 on the dimensions for diarrhoea and constipation on the Gastrointestinal symptoms rating scale (GSRS)
Mentally and physically fit to complete questionnaires during the study period

Exclusion Criteria:

Known or genic gastrointestinal diseasewith 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-inflammtory medication (including NSAIDs)

Healthy controls

Inclusion Criteria:

Age ≥ 18 years
Informed consent signed by the study participant
Mentally and physically fit to complete questionnaires during the study period

Exclusion Criteria:

Previous abdominal surgery
A hypertonic condition demanding medical treatment
Diagnosed psychiatric disease
Lactose intolerance
Usage of medical prescribed medications, expect oral contraceptives, during the 14 days preceding study start
Premenstrual syndrome
Pregnant or breast feeding
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.