Effect of Colon Delivered Vitamin B2 on Gut Microbiota and Related Health Biomarkers in Healthy Older Adults

Study Overview
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Brief Summary
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The goal of this intervention study (clinical trial) is to investigate the effect of colon-delivered Riboflavin (vitamin B2) on the faecal microbial composition and diversity in older healthy subjects (50 -70 years of age)

Official Title
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Effect of Colon Delivered Vitamin B2 on Gut Microbiota and Related Health Biomarkers in Healthy Older Adults

Conditions
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Quality of Life

Intervention / Treatment
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* Dietary Supplement: Riboflavin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants must be willing and able to give written informed consent and to understand, to participate, and to comply with the clinical study requirements. Between 50 and 70 years of age. Has a BMI of between 18.5 - 30 Kg/m2. Participants have had a stable body weight (≤5 % change) over the past 3-months. Is in general good health, as determined by interview and vital signs (blood pressure, heart rate, pulse) by the investigator. Willing to avoid consuming gut microbiome modulating dietary supplements, prebiotic, probiotic, or fibre-rich supplements, and, within 4 weeks prior to the baseline visit, until the end of the study. Maintain current level of physical activity. Willing to consume the investigational product daily for the duration of the study. Female participants in menopause for at least the last one year. - Exclusion Criteria: Are hypersensitive to any of the components of the test product. Has taken antibiotics within the previous 3 months prior to Baseline (Visit2) Is currently using systemic steroids, systemic antibiotics, proton pump inhibitors, H2 blocker, antacid, metformin, or immunosuppressant medication. Participant has a history of drug and/or alcohol abuse at the time of enrolment (Drinks more than nationally recommended units per week (>11 units for women; >17 units for men); Is currently in treatment for alcohol/substance abuse; Has been diagnosed with alcohol/substance abuse disorder). Is a smoker or vaper. Vegetarian or vegan. Has made any major dietary changes in the past 3 months prior to Baseline (Visit 2). Planned major changes in the lifestyle (i.e., diet, dieting, exercise level, significant travel) during the duration of the study. Has a currently active eating disorder. Has food allergies or other issues with foods that would preclude the intake of the study products, as determined by the study investigator. Is having a typical fibre intake >30 g fibre/day. Has an active gastrointestinal disorder or previous gastrointestinal surgery, which in the opinion of the investigator would impact the study outcomes. If taking chronic medications (e.g., anti-hypertensive medications), they must have been taking the product for at least two months to screening and agree to maintain the same dosage throughout the study. Has severe or uncontrolled type 2 diabetes, psychiatric disorder, gastrointestinal disease (i.e., diarrhoea, Crohn's disease, ulcerative colitis, IBS, diverticulosis, stomach or duodenal ulcers respiratory or cardiac illness or any other condition which in the opinion of the investigator would impact the study outcomes. Has a current or history of any gastrointestinal cancer Are severely immunocompromised (HIV positive, transplant patient, on anti-rejection medications, on a steroid for >30 days, or chemotherapy or radiotherapy with the last year). Experiences alarm features such as weight loss, rectal bleeding, a recent change in bowel habit (<3 months). Have a current malignant disease or any concomitant end-stage organ disease. Individuals who, in the opinion of the investigator are considered to be poor attendees or unlikely for any reason to be able to comply with the trial. Participants may not be receiving treatment involving experimental drugs. If the participant has been in a recent experimental trial, these must have been completed not less than 60 days prior to this study. Participants who have undergone intensive skin treatments (e.g. laser treatment or skin related surgery) in the last 3 months. If taking any dietary supplements or medications known to affect skin health or other trial measures (resveratrol, ginkgo biloba, ginseng, fruit powder extracts and DHA). Has a skin condition likely to interfere with skin assessments (e.g., eczema, dermatitis, any open skin wounds, reactive and sensitive skin). -

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 70 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: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized, double-blind, placebo-controlled, parallel trial
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Low dose<br>Daily dose of 1.4 mg of Vitamin B2 (Riboflavin) once a day for 12 weeks | Dietary Supplement: Riboflavin<br>* Colon delivered vitamin B2 (Riboflavin) for 12 weeks<br>|
| Experimental: Mid dose<br>Daily dose of 10 mg of Vitamin B2 (Riboflavin) once a day for 12 weeks | Dietary Supplement: Riboflavin<br>* Colon delivered vitamin B2 (Riboflavin) for 12 weeks<br>|
| Experimental: high dose<br>Daily dose of 75 mg Vitamin B2 (Riboflavin) once a day for 12 weeks | Dietary Supplement: Riboflavin<br>* Colon delivered vitamin B2 (Riboflavin) for 12 weeks<br>|
| Placebo Comparator: Placebo<br>One capsule of 570 mg (consisting of microcrystalline cellulose) once a day for 12 weeks | Dietary Supplement: Riboflavin<br>* Colon delivered vitamin B2 (Riboflavin) for 12 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Faecal microbial composition and diversity | To assess the changes of faecal microbial composition and diversity from baseline to 12 weeks supplementation of three different doses of colon delivered vitamin B2 to compare the changes to placebo. levels, and alpha and beta diversity indices at the genus and species level as measured by metagenomic based profiles at baseline and at week 12 | from baseline to 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Faecal microbial metabolites fatty acid content at baseline and week 12 | Faecal microbial metabolites measured as short-chain fatty acid content at baseline and week 12 | Intestinal inflammation as assessed by faecal calprotectin at baseline and at week 12 | 
| Intestinal inflammation | Intestinal barrier integrity as assessed by sCD14 at baseline and at week 12 | from baseline to 12 weeks | 
| Intestinal barrier integrity | Oxidative stress level measured as free thiol content in blood at baseline and at week 12 | from baseline to 12 weeks | 
| Oxidative stress in blood | Oxidative stress level measured as free thiol content in blood at baseline and at week 12 | from baseline to 12 weeks | 
| Inflammatory status in blood | Systemic inflammation measured as high sensitive C reactive protein (hs-CRP) in blood at baseline and at week 12. | from baseline to 12 weeks | 
| Gastrointestinal symptoms | Gastrointestinal symptoms as assessed by Gastrointestinal Symptom Rating Scale (GSRS).The GSRS is a 15 items questionnaire combined into five symptom clusters i.e Reflux, Abdominal pain, Indigestion, Diarrhoea and Constipation. The GSRS has a seven-point graded Likert-type scale where 1 represents absence of troublesome symptoms and 7 represents very troublesome symptoms.(GSRS) at baseline and at week 12. | from baseline to 12 weeks | 
| health-related quality of life | Quality of life as assessed by short form survey-36 (SF-36) questionnaires at baseline and at week 12. The SF-36 is a self-administered questionnaire comprising 36-items measuring eight health domains: physical functioning (10 items), role limitation due to physical health problems (4 items), bodily pain (2 items), general health perceptions (5 items), vitality (4 items), social functioning (2 items), role limitations due to emotional problems (3 items), and general mental health (5 items). These outcomes will be grouped as a physical component summary and a mental component summary. The norm data is 0-100, and the health-related quality of life increases as the scores increase. | from baseline to 12 weeks | 
| Stool consistency | Stool consistency (Bristol Stool Scale), as reported in the daily eDiary app (at baseline and week 12). Participants will identify each bowel movement 'type' using the Bristol Stool Scale (Type 1 = hard stool difficult to pass [classified as severe constipation]; Type 7 = watery, entirely liquid stool [classified as severe diarrhea]). 'Normal' stool is considered to be Types 3 and 4; and Types 6 and 7 would be considered to suggest mild and severe diarrhea, respectively. | from baseline to 12 weeks | 
| Stool frequency | Stool frequency, as reported in the daily eDiary app (at baseline and week 12). | from baseline to 12 weeks | 
| Systemic vitamin status | The concentration of B vitamins in blood at baseline | from baseline to 12 weeks | 
| Faecal physiological pH | Faecal physiological parameters measured as pH potential at baseline and at week 12. | from baseline to 12 weeks | 
| Faecal microbial composition and diversity at week 4 | Faecal microbial composition at phylum, genus, and species levels, and alpha and beta diversity indices at the genus and species level as measured by metagenomic based profiles at baseline and at week 4. | from baseline to 4 weeks | 
| Microbial metabolites at week 4 | Faecal microbial metabolites measured as short-chain fatty acid content at baseline and week 4. | from baseline to 4 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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microbiota, Riboflavin, ShortChain fatty acids, vitaminB2