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

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)

Study Overview

• Status: Recruiting
• Conditions: Quality of Life
• Intervention / Treatment: Dietary supplement: Riboflavin

• Study Type: Interventional
• Enrollment (Estimated): 348
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Andrea Doolan; Phone Number: +353 21 430 7442; Email: adoolan@atlantiatrials.com
• Study Contact Backup: Name: Barry Skillngton; Phone Number: +353 21 430 7442; Email: bskillington@atlantiatrials.com

Study Locations

• Ireland
  • Cork, Ireland
    • Recruiting
    • Atlantia Food Clinical Trials, 1st Floor, Block C, Heron House, Blackpool Retail Park, Cork
    • Contact: Shauni Fitzgerald; Email: sfitzgerald@atlantiatrials.com
    • Contact: Aisling Harrington; Phone Number: aharrington@atlantiatrials.com; Email: aharrington@atlantiatrials.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Participants must be willing and able to give written informed consent and to understand, to participate, and to comply with the clinical study requirements.
2. Between 50 and 70 years of age.
3. Has a BMI of between 18.5 - 30 Kg/m2.
4. Participants have had a stable body weight (≤5 % change) over the past 3-months.
5. Is in general good health, as determined by interview and vital signs (blood pressure, heart rate, pulse) by the investigator.
6. 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.
7. Maintain current level of physical activity.
8. Willing to consume the investigational product daily for the duration of the study.
9. Female participants in menopause for at least the last one year. -

Exclusion Criteria:

1. Are hypersensitive to any of the components of the test product.
2. Has taken antibiotics within the previous 3 months prior to Baseline (Visit2)
3. Is currently using systemic steroids, systemic antibiotics, proton pump inhibitors, H2 blocker, antacid, metformin, or immunosuppressant medication.
4. 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).
5. Is a smoker or vaper.
6. Vegetarian or vegan.
7. Has made any major dietary changes in the past 3 months prior to Baseline (Visit 2).
8. Planned major changes in the lifestyle (i.e., diet, dieting, exercise level, significant travel) during the duration of the study.
9. Has a currently active eating disorder.
10. Has food allergies or other issues with foods that would preclude the intake of the study products, as determined by the study investigator.
11. Is having a typical fibre intake >30 g fibre/day.
12. Has an active gastrointestinal disorder or previous gastrointestinal surgery, which in the opinion of the investigator would impact the study outcomes.
13. 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.
14. 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.
15. Has a current or history of any gastrointestinal cancer
16. 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).
17. Experiences alarm features such as weight loss, rectal bleeding, a recent change in bowel habit (<3 months).
18. Have a current malignant disease or any concomitant end-stage organ disease.
19. 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.
20. 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.
21. Participants who have undergone intensive skin treatments (e.g. laser treatment or skin related surgery) in the last 3 months.
22. 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).

23. Has a skin condition likely to interfere with skin assessments (e.g., eczema, dermatitis, any open skin wounds, reactive and sensitive skin).

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Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

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

What is the study measuring?

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
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
Stool frequency	Stool frequency, as reported in the daily eDiary app (at baseline and week 12).	from baseline to 12 weeks
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
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
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
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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Skin barrier integrity	Skin barrier integrity measured as trans-epidermal water loss (TEWL) g/m²/h at baseline and at week 12.	from baseline to 12 weeks
Skin hydration	Skin hydration measured using corneometry from 0 (no water at all) to 120 (on water) at baseline and at week 12.	from baseline to 12 weeks
Objective skin-health	Objective skin-health assessment completed by the participant using Likert scale (from not at al to very much) at baseline and at week 12.	from baseline to 12 weeks

Collaborators and Investigators

• Sponsor: DSM Nutritional Products, Inc.
• Collaborators: Atlantia Food Clinical Trials
• Investigators: Principal Investigator: Prof Timothy Dinan, Cork University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): December 12, 2022
• Primary Completion (Estimated): May 29, 2024
• Study Completion (Estimated): May 29, 2024

Study Registration Dates

• First Submitted: February 16, 2023
• First Submitted That Met QC Criteria: March 27, 2023
• First Posted (Actual): April 7, 2023

Study Record Updates

• Last Update Posted (Actual): September 8, 2023
• Last Update Submitted That Met QC Criteria: September 6, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: microbiota; Riboflavin; vitaminB2; ShortChain fatty acids
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Photosensitizing Agents; Dermatologic Agents; Micronutrients; Vitamins; Vitamin B Complex; Riboflavin
• Other Study ID Numbers: 2020-11-11-VITB2

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No