Clinical trial NCT02929459: Effects of Riboflavin on Faecalibacterium Prausnitzii and the Gut Microbiota
Official title: Effects of Oral Riboflavin Supplementation on the Growth of Faecalibacterium Prausnitzii and the Impact on the Gut Microbiota: A Randomized, Double-blind, Placebo-controlled Human Intervention Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Gut Microbiota
Keywords: Gut Microbiota
Riboflavin
Vitamin B2
oGTT
Faecalibacterium prausnitzii
Lead sponsor: DSM Nutritional Products, Inc.
Sponsor class: INDUSTRY
First posted: 2016-10-11
Enrollment: 105
Sex: ALL
Minimum age (years): 20
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The purpose of this trial is to investigate comprehensively the effect of riboflavin supplementation on the abundance of F. prausnitzii and on other members of the gut microbiota in faeces of healthy volunteers. Additionally it will be assessed whether riboflavin supplementation affects the abundance of potentially pathogenic bacteria such as adherent invasive E. coli (AIEC). Finally, the effect of riboflavin supplementation on the production of Short Chain Fatty Acids, the release of gut hormones and potential changes in glucose homeostasis and appetite perception will be assessed.


Eligibility criteria: Inclusion Criteria:

* Males or Females, age 20 - 60 years
* Participant is willing to stick to his/her normal habitual diet excluding consumption of any unusual high energy-rich or fat-rich meals or prolonged fasting, etc. throughout the study period
* Participant is willing to maintain his/her habitual physical activity patterns throughout the study period
* Participant has been stable in body-weight within the last 6 months
* Participant has no health conditions that would prevent him/her from fulfilling the study requirements as judged by the investigator on the basis of medical history and routine laboratory test results
* Participant has a body mass index (BMI) of ≥18.5 and ≤ 24.9 kg/m2 at screening
* Participant is willing to refrain from consuming alcoholic drinks 24 h prior to test days (V2 - V3)
* Participant is not smoking
* Participant is able and motivated to comply with protocol requirements like for instance take the investigational product the way it is prescribed and to do the tests
* Participant understands the study procedures and signs forms providing informed consent to participate in the study

Exclusion Criteria:

* Participant has abnormal clinical chemistry and haematology laboratory test results of clinical significance that in the judgment of the investigator would interfere with the participant's ability to comply with the study protocol (which might confound the interpretation of the study results), or put the participant at undue risk
* Participants with a history of GI disorders that are likely to interfere with the mode of action of the test product
* Participant has donated more than 300 mL of blood during the three months prior to screening
* Participant has a history, in the judgment of the investigator, of a psychological illness or condition such as to interfere with the participant's ability to understand the requirements of the study
* Use of antibiotics or signs of active systemic infection in the last 6 months
* Participants who are on hypocaloric/hypercaloric diet aiming for weight loss/gain
* Participant has a history or presence of cancer in the prior two years, except for non-melanoma skin cancer
* Participant is pregnant, planning to be pregnant during the study period, lactating, or women of childbearing potential who are unwilling to commit to the use of a medically approved form of contraception throughout the study period. The method of contraception must be recorded in the source documentation
* Regular use of dietary supplements e.g. riboflavin, fish oil, 1 month prior to study inclusion
* Participant has had exposure to any non-registered drug product within 30 days prior to the screening visit
* Recent history of (within 12 months of screening visit) or strong potential for alcohol or substance abuse. Alcohol abuse is defined as \>60g (men) / 40g (women) pure alcohol per day (1.5 l / 1 l beer resp. 0.75 l / 0.5 l wine)
* Participant has a known allergy or sensitivity to study product or any ingredients of the study product or meals provided
* Use of commercially available probiotic, prebiotic and other supplements that may affect the gut microbiota

Primary outcomes:
measure: Number of F. prausnitzii per gram faeces
timeFrame: 2 weeks
Secondary outcomes:
measure: Bacterial composition (diversity and quantity of anaerobic microbiota) per gram faeces
timeFrame: 2 weeks
measure: Production of short chain fatty acids (SCFA) in faeces
timeFrame: 2 weeks
measure: Gastrointestinal (GI) comfort (bloating, flatulence)
timeFrame: 2 weeks
measure: Oral Glucose Tolerance Test: blood glucose
timeFrame: 2 weeks
measure: Oral Glucose Tolerance Test: plasma insulin
timeFrame: 2 weeks
measure: Oral Glucose Tolerance Test: Glucagon-like Peptide 1 (GLP-1)
timeFrame: 2 weeks
measure: Oral Glucose Tolerance Test: Glucagon-like Peptide 2 (GLP-2)
timeFrame: 2 weeks
measure: Oral Glucose Tolerance Test: ghrelin
timeFrame: 2 weeks
measure: Oral Glucose Tolerance Test: Appetite feelings during the test
timeFrame: 2 weeks
measure: Changes in stool characteristics: faeces pH
timeFrame: 2 weeks
measure: Changes in stool characteristics: dry weight
timeFrame: 2 weeks
measure: Changes in gut permeability related biomarkers: fatty-acid-binding proteins (I-FABP (plasma))
timeFrame: 2 weeks
measure: Changes in gut permeability related biomarkers: SM-22 (serum)
timeFrame: 2 weeks
measure: Riboflavin concentration in faeces
timeFrame: 2 weeks
measure: Riboflavin concentration in plasma
timeFrame: 2 weeks
Other outcomes:
Locations:
city: Groningen
country: Netherlands
facility: Medical Microbiology, UMCG Groningen
Study officials:
affiliation: Medical Microbiology UMCG Groningen
name: Hermie J.M. Harmsen, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Liu L, Sadaghian Sadabad M, Gabarrini G, Lisotto P, von Martels JZH, Wardill HR, Dijkstra G, Steinert RE, Harmsen HJM. Riboflavin Supplementation Promotes Butyrate Production in the Absence of Gross Compositional Changes in the Gut Microbiota. Antioxid Redox Signal. 2023 Feb;38(4-6):282-297. doi: 10.1089/ars.2022.0033. Epub 2022 Oct 10.