History of Changes for Study: NCT06333717

Impact of Whole Grain Rye Bread on Health (FBS)

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Version	A	B	Submitted Date	Changes
1			March 20, 2024	None (earliest Version on record)

Study Identification


Unique Protocol ID:	Dnr 2020-03709
Brief Title:	Impact of Whole Grain Rye Bread on Health (FBS)
Official Title:	Impact of Whole Grain Rye Bread on Modulating Microbiota-gut-brain Axis in Healthy Subjects
Secondary IDs:

Study Status


Record Verification:	March 2024
Overall Status:	Completed
Study Start:	March 3, 2021
Primary Completion:	March 3, 2021 [Actual]
Study Completion:	November 5, 2021 [Actual]

First Submitted:	February 28, 2024
First Submitted that Met QC Criteria:	March 20, 2024
First Posted:	March 27, 2024 [Actual]

Last Update Submitted that Met QC Criteria:	March 20, 2024
Last Update Posted:	March 27, 2024 [Actual]

Sponsor/Collaborators


Sponsor:	Örebro University, Sweden
Responsible Party:	Sponsor
Collaborators:

Oversight


U.S. FDA-regulated Drug:	No
U.S. FDA-regulated Device:	No
Data Monitoring:	No

Study Description

Brief Summary:

This randomized controlled trial aims to study how a high intake of a fibre-rich bread affects the composition and functioning of the gut microbiota in healthy subjects, and how this, in turn, impacts on the release of gut peptides, intestinal permeability, stress and cognitive performance.

Detailed Description:

Healthy subjects will be recruited for a 3-week, randomized, parallel-controlled study. Subjects that are eligible to take part in the study will be blinded and randomly allocated to consume a fibre-rich bread or a control bread daily for 3 weeks. Measurements of biomarkers related to the gut-brain axis, microbiota composition and functioning, intestinal permeability, stress and cognitive functioning will be conducted on two separate test days, at baseline and after the 3 weeks intervention. On both test days (day 0 and day 21) subjects will come to the study centre after a 10 hours overnight fast and will deliver faecal samples collected at home. At the study centre, blood samples will be collected and a device for continuous assessment of autonomic nervous system response (Biopac) will be placed. Subjects will drink a multisugar solution and urine samples will be collected for gut permeability analysis. Sugar solution intake will be followed by a baseline period during which participants will rest for 30 minutes to adapt to the laboratory setting. After the baseline period, subjects will conduct a stress test and cognitive tests. Visual analogue scales (VAS) to assess momentary perceived stress levels and saliva samples will be collected before and after the stress test. The study subjects will also complete questionnaires at both visits (food frequency questionnaire, food diary, physical activity, gastrointestinal symptom rating scale, Euro Quality of Life).

Conditions


Conditions:	Healthy Diet
Keywords:	dietary fibre microbiota gut-brain axis

Study Design


Study Type:	Interventional
Primary Purpose:	Prevention
Study Phase:	Not Applicable
Interventional Study Model:	Parallel Assignment
Number of Arms:	2
Masking:	Double (Participant, Investigator)
Allocation:	Randomized
Enrollment:	33 [Actual]

Arms and Interventions

Arms	Assigned Interventions
Experimental: High-fibre bread Six slices (180 g) of whole grain rye bread divided over the meals during the day for 3 weeks	Dietary Supplement: Whole grain bread Consumption of high-fibre bread as a dietary supplementation
Placebo Comparator: Control bread Six slices (180 g) of control bread containing refined wheat and oat flour divided over the meals during the day for 3 weeks	Dietary Supplement: Control bread Consumption of control bread as a dietary supplementation

Outcome Measures


Primary Outcome Measures:
1.	Microbiota composition baseline vs after intervention using 16S RNA gene sequencing [ Time Frame: faecal samples collected before and after intake of bread for 3 weeks ] Difference in gut microbiota composition in faecal samples before (baseline) and after intake of six slices of bread for 3 weeks (after intervention) using 16S RNA gene sequencing
Secondary Outcome Measures:
1.	Microbiota composition whole grain rye bread vs control bread using 16S RNA gene sequencing [ Time Frame: faecal samples collected before and after intake of bread for 3 weeks ] Difference in gut microbiota composition in faecal samples between the study arms using 16S RNA gene sequencing
2.	Concentrations of circulatory short-chain fatty acids SCFA [ Time Frame: blood samples collected before and after intake of bread for 3 weeks ] Difference in blood levels of SCFA between and within intervention groups after intake of bread for 3 weeks
3.	Concentrations of faecal SCFA [ Time Frame: faecal samples collected before and after intake of bread for 3 weeks ] Difference in faecal levels of SCFA between and within intervention groups after intake of bread for 3 weeks
4.	Concentrations of blood glucagon like peptide-1 (GLP-1) [ Time Frame: blood samples collected before and after intake of bread for 3 weeks ] Difference in blood levels of GLP-1 between and within intervention groups after intake of bread for 3 weeks
5.	Concentrations of blood glucagon like peptide-2 (GLP-2) [ Time Frame: blood samples collected before and after intake of bread for 3 weeks ] Difference in blood levels of GLP-2 between and within intervention groups after intake of bread for 3 weeks
6.	Concentrations of blood peptide YY (PYY) [ Time Frame: blood samples collected before and after intake of bread for 3 weeks ] Difference in blood levels of PYY between and within intervention groups after intake of bread for 3 weeks
7.	Concentrations of blood gastric inhibitory polypeptide (GIP) [ Time Frame: blood samples collected before and after intake of bread for 3 weeks ] Difference in blood levels of GIP between and within intervention groups after intake of bread for 3 weeks
8.	Concentrations of blood neuroactive peptide Y (NPY) [ Time Frame: blood samples collected before and after intake of bread for 3 weeks ] Difference in blood levels of NPY between and within intervention groups after intake of bread for 3 weeks
9.	Concentrations of blood brain-derived neurotrophic factor (BDNF) [ Time Frame: blood samples collected before and after intake of bread for 3 weeks ] Difference in blood levels of BDNF between and within intervention groups after intake of bread for 3 weeks
10.	Concentrations of blood cytokines [ Time Frame: blood samples collected before and after intake of bread for 3 weeks ] Difference in blood levels of cytokines between and within intervention groups after intake of bread for 3 weeks
11.	Concentrations of blood alkylresorcinols [ Time Frame: blood samples collected before and after intake of bread for 3 weeks ] Difference in blood levels of alkylresorcinols between and within intervention groups after intake of bread for 3 weeks
12.	Concentrations of blood lipopolysaccharide-binding protein (LBP) [ Time Frame: blood samples collected before and after intake of bread for 3 weeks ] Difference in blood levels of LBP between and within intervention groups after intake of bread for 3 weeks
13.	Concentrations of blood soluble CD-14 (sCD-14) [ Time Frame: blood samples collected before and after intake of bread for 3 weeks ] Difference in blood levels of sCD-14 between and within intervention groups after intake of bread for 3 weeks
14.	Concentrations of sugars in urine [ Time Frame: urine samples collected before and after intake of bread for 3 weeks ] Difference on intestinal permeability between and within intervention groups after intake of bread for 3 weeks measured by the excretion of sugars contained in a multi-sugar solution
15.	Concentrations of saliva cortisol during stress test [ Time Frame: Saliva samples collected before the stress test, after the introduction phase, directly after the acute stress phase, 5 minutes, 10-15 minutes, 60 minutes, and 75 minutes after the stress test ] Difference in saliva levels of cortisol produced during stress test between and within intervention groups after intake of bread for 3 weeks
16.	Concentrations of saliva alpha-amylase during stress test [ Time Frame: Saliva samples collected before the stress test, after the introduction phase, directly after the acute stress phase, 5 minutes, 10-15 minutes, 60 minutes, and 75 minutes after the stress test ] Difference in saliva levels of a-amylase produced during stress test between and within intervention groups after intake of bread for 3 weeks
Other Outcome Measures:
1.	Gastrointestinal symptoms measured by Gastrointestinal Symptom Rating Scale in Irritable Bowel Syndrome (GSRS-IBS) [ Time Frame: 3 weeks ] Difference in the frequency and severity of gastrointestinal symptoms between and within intervention groups after the intake of bread for 3 weeks. The GSRS-IBS contains 13 self-report items rated on a 6-point Likert scale ranging from 1 (no discomfort at all) to 7 (very severe discomfort). Total scores range from 0 to 78.
2.	Food habits measured by an electronic food frequency questionnaire Mealq [ Time Frame: 3 weeks ] Survey of participants' food habits before and during the intake of bread for 3 weeks
3.	Food habits measured by a Food diary [ Time Frame: 3 days ] Survey of participants' food habits before and during the intake of bread for 3 weeks
4.	Physical activity measured by the International Physical Activity Questionnaire (IPAQ) [ Time Frame: 3 days ] Survey of participants' physical activities before and during the intake of bread for 3 weeks. The IPAQ contains 7 self-report questions and the categorical score is divided into 3 levels: low (less than 600 metabolic equivalent-minutes/week), moderate (at least 600 metabolic equivalent-minutes/week) or high (at least 1500 metabolic equivalent-minutes/week).
5.	Quality of life measured by the Euro Quality of Life questionnaire [ Time Frame: once before and after intake of bread for 3 weeks ] Survey of participants' well-being before and during the intake of bread for 3 weeks. It records the patient's self-rated health on a vertical visual analogue scale where the endpoints are labelled from 0 (worst imaginable health state) to 100 (best imaginable health state).
6.	Perceived stress measured by a Visual analog scale questionnaire [ Time Frame: before the stress test, after the introduction phase, directly after the acute stress phase, 5 minutes, 10-15 minutes, 60 minutes, and 75 minutes after the stress test ] Difference in the perceived stress during a stress test between and within intervention groups after the intake of bread for 3 weeks
7.	Cognitive control using Eriksen flanker task (Flanker task) [ Time Frame: once before and after intake of bread for 3 weeks ] Difference in cognitive control between and within intervention groups after the intake of bread for 3 weeks
8.	Working memory performance using a modified N-back task combined with recent-probes item-recognition task (Sternberg task) [ Time Frame: once before and after intake of bread for 3 weeks ] Difference in working memory between and within intervention groups after the intake of bread for 3 weeks
9.	Electrocardiogram (ECG) using the Biopac system [ Time Frame: once before and after intake of bread for 3 weeks ] Difference in heart rate variability during a stress test between and within intervention groups after the intake of bread for 3 weeks
10.	Electrodermal activity (EDA) using the Biopac system [ Time Frame: once before and after intake of bread for 3 weeks ] Difference in skin conductivity during a stress test between and within intervention groups after the intake of bread for 3 weeks. Electrodes to measure EDA will be placed on the subjects' left palm. Skin conductivity measures will include skin conductivity level (SCL), the number of skin conductivity responses (SCR), and the amplitude of SCR.

Eligibility


Minimum Age:	18 Years
Maximum Age:	44 Years
Sex:	All
Gender Based:
Accepts Healthy Volunteers:	Yes
Criteria:	Inclusion Criteria: Age 18-44 years Body mass index (BMI) 18,5-30 kg/m2 (normal weight or overweight) Exclusion Criteria: Significant acute or chronic illness, including an inflammatory or a functional disease of gastrointestinal track and psychiatric and psychological disorders Anxiety or depression (according to Hospital Anxiety and Depression Scale (HADS score) and Depression Anxiety Stress Scale (DASS-21 score)) Use of a medication that may interfere with the study (e.g. cannabis, antipsychotics, anxiolytics, antidepressants, proton-pump inhibitors) Abuse of alcohol or drugs (according to AUDIT score) Use of antibiotic medication within the past 3 months before the study Use of laxative or anti-diarrhoea medication within the past 3 months before the study Regular consumption of probiotic or prebiotic product for the past 6 weeks before the study A diet that may interfere with the study (such as gluten free or low-carb diet) Smoking Pregnancy or breastfeeding Premenopausal female with irregular or short menstruation cycle and not using hormonal contraception Colour blindness, dyslexia or dyscalculia Unable to absent from caffeine, alcohol or intense exercise for 12 hours prior measurements.

Contacts/Locations


Study Officials:	Rebecca Wall, PhD Principal Investigator Örebro University, Sweden
Locations:	Sweden
	Örebro University Örebro, Sweden

IPDSharing


Plan to Share IPD:	No

References


Citations:
Links:
Available IPD/Information: