Colon-delivered Riboflavin and Gut Microbiota Composition

Official title

The Benefit of Colon-delivered Riboflavin (Riboflavin-cd) vs. Conventional Riboflavin on Gut Microbiota Composition and Metabolic Output in Healthy Aging Subjects - a Pilot Proof of Concept Study

Overview

Recent studies suggest B-vitamins such as riboflavin to possess prebiotic-like effects. However, there is still a lack of understanding of the exact host health benefits vs. conventional systemically available vitamin forms. The present study explores the benefit of colon-delivered vitamin B2 vs. conventional vitamin B2 in comparison to placebo in an aging population on gut microbiota and metabolic activity as well as gut health.

Interventions

• Dietary supplement Colon-delivered riboflavin
  10 mg of colon-delivered riboflavin
• Dietary supplement Conventional riboflavin
  10 mg of conventional riboflavin
• Other Microcrystalline Cellulose
  10 mg microcrystalline cellulose

Primary outcome measures

• Microbial alpha diversity [Time frame: 4 weeks' daily consumption of 10 mg of colon delivered riboflavin (riboflavin-cd)]

Secondary outcome measures (12)

• Microbial alpha diversity [Time frame: 8 weeks' daily consumption of 10 mg of colon delivered riboflavin (riboflavin-cd) including 5 g of dietary fiber inulin per day as a standardised addition to the subjects daily diet from week 4 to week 8.]
• Microbial composition [Time frame: 8 weeks' daily consumption of 10 mg of colon delivered riboflavin (riboflavin-cd) including 5 g of dietary fiber inulin per day as a standardised addition to the subjects daily diet from week 4 to week 8.]
• Faecal organic acid [Time frame: 8 weeks' daily consumption of 10 mg of colon delivered riboflavin (riboflavin-cd) including 5 g of dietary fiber inulin per day as a standardised addition to the subjects daily diet from week 4 to week 8.]
• Faecal riboflavin [Time frame: 8 weeks' daily consumption of 10 mg of colon delivered riboflavin (riboflavin-cd) including 5 g of dietary fiber inulin per day as a standardised addition to the subjects daily diet from week 4 to week 8.]
• Fecal redox potential [Time frame: 8 weeks' daily consumption of 10 mg of colon delivered riboflavin (riboflavin-cd) including 5 g of dietary fiber inulin per day as a standardised addition to the subjects daily diet from week 4 to week 8.]
• fecal pH [Time frame: 8 weeks' daily consumption of 10 mg of colon delivered riboflavin (riboflavin-cd) including 5 g of dietary fiber inulin per day as a standardised addition to the subjects daily diet from week 4 to week 8.]
• Fecal calprotectin [Time frame: 8 weeks' daily consumption of 10 mg of colon delivered riboflavin (riboflavin-cd) including 5 g of dietary fiber inulin per day as a standardised addition to the subjects daily diet from week 4 to week 8.]
• Plasma Intestinal barrier markers [Time frame: 8 weeks' daily consumption of 10 mg of colon delivered riboflavin (riboflavin-cd) including 5 g of dietary fiber inulin per day as a standardised addition to the subjects daily diet from week 4 to week 8.]
• Gastrointestinal complaints [Time frame: 8 weeks' daily consumption of 10 mg of colon delivered riboflavin (riboflavin-cd) including 5 g of dietary fiber inulin per day as a standardised addition to the subjects daily diet from week 4 to week 8.]
• Stool consistency and frequency [Time frame: 8 weeks' daily consumption of 10 mg of colon delivered riboflavin (riboflavin-cd) including 5 g of dietary fiber inulin per day as a standardised addition to the subjects daily diet from week 4 to week 8.]
• Quality of life (Short-Form Health Survey (SF-36)) [Time frame: 8 weeks' daily consumption of 10 mg of colon delivered riboflavin (riboflavin-cd) including 5 g of dietary fiber inulin per day as a standardised addition to the subjects daily diet from week 4 to week 8.]
• Investigational product (IP) perceived benefit [Time frame: 8 weeks' daily consumption of 10 mg of colon delivered riboflavin (riboflavin-cd) including 5 g of dietary fiber inulin per day as a standardised addition to the subjects daily diet from week 4 to week 8.]

Eligibility criteria

Inclusion criteria

• Individuals providing written informed consent for participation in the study and data processing
• Female and males between 50 and 70 years of age
• For females only: Menopausal as marked by at least 1 year since the last menstrual bleeding
• Individuals with a BMI between 18.5 - 29.9 Kg/m2
• Individuals with stable body weight (≤5% change) over the past 3 months prior to V1
• Individuals with self-reported moderate bowel complaints in at least last 3 months prior to V1
• Individuals with GSRS score suggestive of moderate bowel complaints, as assessed at V1, for the average condition over the 4 last weeks (all GSRS items have to be answered at V1): • indigestion score 3-5 or constipation score 3-5 or diarrhoea score 3-5
• Individuals with a general good health, as determined by questioning, clinical examination and vital signs (blood pressure, pulse rate) by the investigator at V1
• Individuals willing to avoid consuming gut microbiome modulating dietary supplements, prebiotic, probiotic, synbiotic or fibre-rich supplements during the entire study duration
• Individuals willing to maintain current level of physical activity throughout the entire study duration
• If individuals are taking chronic medications (e.g., antihypertensive medications), they must be willing and expected to maintain the same dosage throughout the study

Exclusion criteria

• Individuals who are hypersensitive/intolerant to any of the components of the Investigational product or the standardised diet addition (inulin)
• Individuals who have taken systemic antibiotics within the previous 3 months prior to Baseline (V2) or are expected to be taking any during the study
• Individuals who consumed microbiome modulating dietary supplements, prebiotic, probiotic, or fibre-rich supplements within 4 weeks prior to the baseline (V2)
• Individuals who are currently regularly using systemic steroids, proton pump inhibitors, H2 blocker, antacids (however, sporadic use during the study if needed is allowed, but not within 8 hours before each visit), metformin if started less than 6 months prior to V1, or immunosuppressant medication.
• Individuals who have a history of drug abuse in the previous 5 years and/or alcohol abuse at the time of enrolment (>11 units/week for women; >17 units/week for men; unit: approx. 125 mL of wine or similar / approx. 30 mL of spirits

/ approx. 280 mL beer or similar); Is currently in treatment for alcohol/substance abuse; Has been diagnosed with alcohol/substance abuse disorder)

• Individuals who are a smoker or vaper
• Individuals who are vegetarian or vegan
• Individuals who have made any major dietary changes in the past 3 months prior to Baseline (V2)
• Individuals who have planned major changes in the lifestyle (i.e., diet, dieting, exercise level, significant travel) during the duration of the study.
• Individuals who have a currently present active eating disorder
• Individuals with self-reported food allergy / intolerance (e.g., lactose, gluten, fructose), as determined by the study investigator
• Clinical significance for any of screening laboratory test results from the blood draw at V1, as per investigator's judgement
• Individuals with a self-reported fibre-rich regular diet, as per investigator's judgement
• Individuals who have a (self-reported) gastrointestinal disorder/disease (e.g., chronic/recurrent diarrhoea, inflammatory bowel disorder, irritable bowel syndrome, diverticulosis, stomach or duodenal ulcers, bile acid malabsorption) or previous gastrointestinal surgery (such as bariatric surgery, colon specific surgical interventions etc.), which in the opinion of the investigator would impact the study outcomes
• Individuals with GSRS assessed at V1 for the average condition over the 4 last weeks prior to V1 for any score (abdominal pain, reflux score, indigestion, constipation, diarrhoea) >5 (all GSRS items have to be answered at V1)
• Individuals who have severe or uncontrolled conditions such as type 2 diabetes (FBG ≥ 150 mg/dl from blood draw at V1), psychiatric disorder, respiratory or cardiac illness or any other condition which in the opinion of the investigator would impact the study outcomes
• Individuals who have a history of any gastrointestinal cancer
• Individuals who are severely immunocompromised
• Individuals with alarm features in the past 3 months prior to V1 such as unintentional weight loss (≤5% change), fever, anorectal problems, blood in stool, vomiting
• 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 study requirements
• If Individuals have been in a recent experimental study, this must have been completed not less than 30 days prior to this study

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Basic science

Study locations

Germany · 1 center

• analyze & realize GmbH — Berlin

Identifiers

NCT: NCT07093463 · DSM/230702 · DSM/011224

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗