Gut MicrobiotaPhase 2NCT02929459
Effects of Riboflavin on Faecalibacterium Prausnitzii and the Gut Microbiota
A Phase 2 study testing Riboflavin Dose 1 and Riboflavin Dose 2 in people with Gut Microbiota, run by dsm-firmenich Switzerland AG at 1 site in Netherlands.
Trial 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. Read more about this study
- Who is it for?
- Ages 20 to 60 yearsHealthy volunteers can take part
- Conditions the study is for
- Gut Microbiota
- What is being tested?
- Riboflavin Dose 1 and Riboflavin Dose 2
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 105 participants
- Where
- 1 siteNetherlands
- Study dates
- 1 Nov 2016to 1 Dec 2019
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 to 60 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
1 site in 1 country.
About this study
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
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.
- Conditions
- Gut Microbiota
- Being tested
- Riboflavin Dose 1, Riboflavin Dose 2, Placebo
- Keywords
- Gut Microbiota, Riboflavin, Vitamin B2, oGTT, Faecalibacterium prausnitzii
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Riboflavin Dose 1Dietary supplement
Also called Vitamin B2
Riboflavin Dose 2Dietary supplement
Also called Vitamin B2
PlaceboOther
| Study group | Role | What they receive |
|---|---|---|
| Riboflavin Dose 1 | Experimental | 100 mg Riboflavin (one capsule) per day for 2 weeks Receives: Dietary Supplement: Riboflavin Dose 1 |
| Riboflavin Dose 2 | Experimental | 50 mg Riboflavin (one capsule) per day for 2 weeks Receives: Dietary Supplement: Riboflavin Dose 2 |
| Placebo | Placebo comparator | 100 mg starch plus 0,5% silica (one capsule) per day for 2 weeks Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of F. prausnitzii per gram faeces
To determine the effect of 2 weeks oral riboflavin supplementation (50 and 100 mg/day) on the number of F. prausnitzii per gram faeces in comparison with placebo
Measured: 2 weeks
Secondary outcomes (15)
Bacterial composition (diversity and quantity of anaerobic microbiota) per gram faeces
To determine the effects of 2 weeks oral riboflavin supplementation (50 and 100 mg/day) on bacterial composition (diversity and quantity of anaerobic microbiota) in comparison with placebo
Measured: 2 weeks
Production of short chain fatty acids (SCFA) in faeces
To determine the effects of 2 weeks oral riboflavin supplementation (50 and 100 mg/day) on the production of short chain fatty acids (SCFA) in faeces in comparison with placebo
Measured: 2 weeks
Gastrointestinal (GI) comfort (bloating, flatulence)
To determine the effects of 2 weeks oral riboflavin supplementation (50 and 100 mg/day) on gastrointestinal (GI) comfort (bloating, flatulence) in comparison with placebo using validated visual analogue scale (VAS) questionnaires
Measured: 2 weeks
Oral Glucose Tolerance Test: blood glucose
In a subgroup of participants, to determine the effects of 2 weeks oral riboflavin supplementation (50 and 100 mg/day) on blood glucose, and plasma insulin, GLP-1, GLP-2 and ghrelin as well as appetite feelings during an oral glucose tolerance test (oGTT) in comparison with placebo
Measured: 2 weeks
Oral Glucose Tolerance Test: plasma insulin
In a subgroup of participants, to determine the effects of 2 weeks oral riboflavin supplementation (50 and 100 mg/day) on blood glucose, and plasma insulin, GLP-1, GLP-2 and ghrelin as well as appetite feelings during an oral glucose tolerance test (oGTT) in comparison with placebo
Measured: 2 weeks
Oral Glucose Tolerance Test: Glucagon-like Peptide 1 (GLP-1)
In a subgroup of participants, to determine the effects of 2 weeks oral riboflavin supplementation (50 and 100 mg/day) on blood glucose, and plasma insulin, GLP-1, GLP-2 and ghrelin as well as appetite feelings during an oral glucose tolerance test (oGTT) in comparison with placebo
Measured: 2 weeks
Oral Glucose Tolerance Test: Glucagon-like Peptide 2 (GLP-2)
In a subgroup of participants, to determine the effects of 2 weeks oral riboflavin supplementation (50 and 100 mg/day) on blood glucose, and plasma insulin, GLP-1, GLP-2 and ghrelin as well as appetite feelings during an oral glucose tolerance test (oGTT) in comparison with placebo
Measured: 2 weeks
Oral Glucose Tolerance Test: ghrelin
In a subgroup of participants, to determine the effects of 2 weeks oral riboflavin supplementation (50 and 100 mg/day) on blood glucose, and plasma insulin, GLP-1, GLP-2 and ghrelin as well as appetite feelings during an oral glucose tolerance test (oGTT) in comparison with placebo
Measured: 2 weeks
Oral Glucose Tolerance Test: Appetite feelings during the test
In a subgroup of participants, to determine the effects of 2 weeks oral riboflavin supplementation (50 and 100 mg/day) on blood glucose, and plasma insulin, GLP-1, GLP-2 and ghrelin as well as appetite feelings during an oral glucose tolerance test (oGTT) in comparison with placebo
Measured: 2 weeks
Changes in stool characteristics: faeces pH
To determine the possible changes in stool characteristics such as faeces pH upon riboflavin supplementation
Measured: 2 weeks
Changes in stool characteristics: dry weight
To determine the possible changes in stool characteristics such as dry weight upon riboflavin supplementation
Measured: 2 weeks
Changes in gut permeability related biomarkers: fatty-acid-binding proteins (I-FABP (plasma))
To determine any possible effect on gut permeability, assessment of permeability related biomarkers: fatty-acid-binding proteins (I-FABP (plasma)) and SM-22 (serum) upon riboflavin supplementation
Measured: 2 weeks
Changes in gut permeability related biomarkers: SM-22 (serum)
To determine any possible effect on gut permeability, assessment of permeability related biomarkers: fatty-acid-binding proteins (I-FABP (plasma)) and SM-22 (serum) upon riboflavin supplementation
Measured: 2 weeks
Riboflavin concentration in faeces
To determine the effects of 2 weeks oral riboflavin supplementation on riboflavin concentration in faeces and plasma
Measured: 2 weeks
Riboflavin concentration in plasma
To determine the effects of 2 weeks oral riboflavin supplementation on riboflavin concentration in faeces and plasma
Measured: 2 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Oct 2016 (estimated)
- Study start1 Nov 2016
- Primary completion1 Oct 2018
- Study completion1 Dec 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Gut MicrobiotaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 105 participants (estimated)
Sponsor and investigators
- Lead sponsor
- dsm-firmenich Switzerland AG
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Hermie J.M. Harmsen, PhD, Principal investigator, Medical Microbiology UMCG Groningen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02929459
- Sponsor's protocol ID
- RiboGut2015
- Status last verified
- Jan 2020
- First submitted
- 6 Oct 2016
- Last updated
- 22 Jan 2020
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
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.
PubMed 35943883
Study at a glance
From the registry record, last updated by the sponsor on 22 Jan 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02929459
- Acronym / sponsor ID
- RiboGut2015
- Conditions
- Gut Microbiota
- Keywords
- Gut Microbiota, Riboflavin, Vitamin B2, oGTT, Faecalibacterium prausnitzii
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 105 participants (estimated)
- Lead sponsor
- dsm-firmenich Switzerland AGIndustry (pharma, biotech, devices)
- Study start
- 1 Nov 2016 (actual)
- Primary completion
- 1 Oct 2018 (actual)
- Study completion
- 1 Dec 2019 (actual)
- First posted
- 11 Oct 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Riboflavin Dose 1 | Experimental | Dietary Supplement: Riboflavin Dose 1100 mg Riboflavin (one capsule) per day for 2 weeks |
| Riboflavin Dose 2 | Experimental | Dietary Supplement: Riboflavin Dose 250 mg Riboflavin (one capsule) per day for 2 weeks |
| Placebo | Placebo comparator | Other: Placebo100 mg starch plus 0,5% silica (one capsule) per day for 2 weeks |
Who may qualify
- Ages
- 20 to 60 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (10 listed)
- 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
Key exclusion criteria (13 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Riboflavin Dose 1Also: Vitamin B2 | Dietary supplement | Riboflavin Dose 1 |
| Riboflavin Dose 2Also: Vitamin B2 | Dietary supplement | Riboflavin Dose 2 |
| Placebo | Other | Placebo |
Primary outcome
Number of F. prausnitzii per gram faeces
Time frame: 2 weeks
To determine the effect of 2 weeks oral riboflavin supplementation (50 and 100 mg/day) on the number of F. prausnitzii per gram faeces in comparison with placebo
15 secondary outcomes
Bacterial composition (diversity and quantity of anaerobic microbiota) per gram faeces
Time frame: 2 weeks
Production of short chain fatty acids (SCFA) in faeces
Time frame: 2 weeks
Gastrointestinal (GI) comfort (bloating, flatulence)
Time frame: 2 weeks
Oral Glucose Tolerance Test: blood glucose
Time frame: 2 weeks
Oral Glucose Tolerance Test: plasma insulin
Time frame: 2 weeks
Oral Glucose Tolerance Test: Glucagon-like Peptide 1 (GLP-1)
Time frame: 2 weeks
Oral Glucose Tolerance Test: Glucagon-like Peptide 2 (GLP-2)
Time frame: 2 weeks
Oral Glucose Tolerance Test: ghrelin
Time frame: 2 weeks
Oral Glucose Tolerance Test: Appetite feelings during the test
Time frame: 2 weeks
Changes in stool characteristics: faeces pH
Time frame: 2 weeks
Changes in stool characteristics: dry weight
Time frame: 2 weeks
Changes in gut permeability related biomarkers: fatty-acid-binding proteins (I-FABP (plasma))
Time frame: 2 weeks
Changes in gut permeability related biomarkers: SM-22 (serum)
Time frame: 2 weeks
Riboflavin concentration in faeces
Time frame: 2 weeks
Riboflavin concentration in plasma
Time frame: 2 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jan 2020.
- Derived from this study: PubMed 35943883Liu 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Hermie J.M. Harmsen, PhD principal investigator
Medical Microbiology UMCG Groningen
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Riboflavin Dose 1 and Riboflavin Dose 2 in people with Gut Microbiota, run by dsm-firmenich Switzerland AG at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Jan 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of F. prausnitzii per gram faeces (time frame: 2 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02929459, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jan 2020.