Crohn DiseaseRISE-UPNCT02538354
The Effect of Riboflavin in Crohn's Disease
A study testing Riboflavin supplementation in people with Crohn Disease, run by University Medical Center Groningen at 1 site in Netherlands.
Trial summary
This study will evaluate if suppelementation of the diet with riboflavin in Crohn's disease patients will result in an increase in the amount of F. prausnitzii. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Crohn Disease
- What is being tested?
- Riboflavin supplementation
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 70 participants
- Where
- 1 siteNetherlands
- Study dates
- Mar 2016to Apr 2017
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Crohn's disease patients
- Age 18-65 years
- Concomitant medication for Crohn's disease is allowed in all groups
Who cannot join
- Swallowing disorders
- Pregnancy and lactation
- Use of antibiotic drugs, probiotics (i.e.Yakult, Vifit, Activia etc) or specific prebiotic supplements in the 3 weeks prior to the riboflavin intervention
- Use of Methotrexate drugs
- Colonoscopy and colon cleansing in last 3 months
- Use of a vitamin B2 supplement, or multivitamin complexes containing vitamin B (i.e. vitamin B-complex) in the 3 weeks prior to the riboflavin intervention
- Severe Crohn's disease (HBI > 12)
Trial locations and contacts
1 site in 1 country.
About this study
Official title: The Effect of Riboflavin Supplementation on Faecalibacterium Prausnitzii in Crohn's Disease
This study will evaluate if suppelementation of the diet with riboflavin in Crohn's disease patients will result in an increase in the amount of F. prausnitzii.
Read the detailed description
Rationale Recent studies show that in patients with Inflammatory Bowel Disease (IBD) a dysbiosis exists in the composition of the intestinal microbiota. In particular, the potentially pathogenic bacterium Escherichia coli (E. coli) is often more abundant in the bowel of IBD patients, and the anaerobic commensal Faecalibacterium prausnitzii (F. prausnitzii) is often reduced. This last mentioned bacteria is known to be abundant in the intestine of healthy individuals. It is known to produce butyrate, which stimulates the intestinal epithelium, and to secrete anti-inflammatory substances.
Riboflavin - also known as vitamin B2 - is required for a wide variety of cellular processes and has an important role in maintaining health in humans. In a pilot intervention with healthy volunteers it is shown that a riboflavin supplement increases the number of F. prausnitzii and results in a higher production of butyrate. In Crohn's disease patients, it is known that the amount of F. prausnitzii in the intestine is generally low. Furthermore, it is known that there is an association between the number of F. prausnitzii bacteria and the length of disease in remission.
This study will evaluate if supplementation of the diet with riboflavin in Crohn's disease patients will result in a similar increase in the amount of F. prausnitzii as in healthy volunteers. In this patient group, an increase in the number of F. prausnitzii bacteria in the bowel may result in a more favourable disease course. This will be assessed with faeces calprotectin and two questionnaires. Additionally the investigators will assess if there is any modulation by riboflavin on the other intestinal bacteria, short chain fatty acids (SCFAs) (such as butyrate), and the pH of the faeces. Finally, the effect of the riboflavin on the permeability of the gut will be evaluated with a Chroom-EDTA test, and a number of different biomarkers of permeability.
Hypothesis The hypothesis is that in Crohn's disease patients, supplementation of the diet with riboflavin results in an increase in the amount of F. prausnitzii, changes in microbial composition, increased fatty acid production, an increase in pH and a reduction of intestinal permeability. These changes might result in a more favourable disease course with less exacerbations.
Study design Prospective clinical study.
Study population and sample size In total 84 Crohn's disease patients will be included in this study, divided into two groups. Group 1 (n=42) will consist of patients with disease in remission (quiescent disease); group 2 (n=42) will consist of patients with active disease. In this study an adaptive design will be used. First 12 patients in the disease in remission group will be analysed. The methods of analysis and safety aspects will be taken into account.
Intervention Supplementation of the normal diet with 1 capsule of 100 mg riboflavin (vitamin B2) during three weeks.
- Conditions
- Crohn Disease
- Being tested
- Riboflavin supplementation
- Keywords
- Riboflavin (vitamin B2), Faecalibacterium prausnitzii
- Medical subject headings
- Crohn Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Riboflavin supplementationDietary supplement
Also called vitamin B2 supplementation
Supplementation of the normal diet with 1 capsule of 100 mg riboflavin (vitamin B2) during three weeks
| Study group | Role | What they receive |
|---|---|---|
| Riboflavin supplementation in quiescent disease | Experimental | Group 1 (n=42) will consist of patients with disease in remission (quiescent disease). Receives: Dietary Supplement: Riboflavin supplementation |
| Riboflavin supplementation in active disease | Experimental | Group 2 (n=42) will consist of patients with active disease. Receives: Dietary Supplement: Riboflavin supplementation |
What is being measured
The primary outcome is the main question the study is designed to answer.
F. Prausnitzii (FISH Analysis).
The faeces is collected at different time points before and after riboflavin supplementation. To investigate the effect of a riboflavin supplement on the number of F. prausnitzii bacteria in the faeces of active and quiescent Crohn's disease patients.
Measured: Different time points up to 6 weeks from start study: Day0, Day7, Day28
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Sep 2015 (estimated)
- Study startMar 2016
- Primary completionApr 2017
- Study completionApr 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (10)Papers the sponsor has linked to this study.
- Other trials for Crohn DiseaseStudies of the same condition, open and under way.
- More trials run by University Medical Center GroningenThe sponsor's other registered studies.
- 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 N/A
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 70 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Medical Center Groningen
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Prof. dr. G. Dijkstra, University Medical Center Groningen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02538354
- Sponsor's protocol ID
- METc 2014/291
- Other IDs
- Protocol ID
- Acronym
- RISE-UP
- Status last verified
- Mar 2020
- First submitted
- 20 Aug 2015
- Last updated
- 3 Apr 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Sartor RB. Microbial influences in inflammatory bowel diseases. Gastroenterology. 2008 Feb;134(2):577-94. doi: 10.1053/j.gastro.2007.11.059.
PubMed 18242222Sokol H, Pigneur B, Watterlot L, Lakhdari O, Bermudez-Humaran LG, Gratadoux JJ, Blugeon S, Bridonneau C, Furet JP, Corthier G, Grangette C, Vasquez N, Pochart P, Trugnan G, Thomas G, Blottiere HM, Dore J, Marteau P, Seksik P, Langella P. Faecalibacterium prausnitzii is an anti-inflammatory commensal bacterium identified by gut microbiota analysis of Crohn disease patients. Proc Natl Acad Sci U S A. 2008 Oct 28;105(43):16731-6. doi: 10.1073/pnas.0804812105. Epub 2008 Oct 20.
PubMed 18936492Fujimoto T, Imaeda H, Takahashi K, Kasumi E, Bamba S, Fujiyama Y, Andoh A. Decreased abundance of Faecalibacterium prausnitzii in the gut microbiota of Crohn's disease. J Gastroenterol Hepatol. 2013 Apr;28(4):613-9. doi: 10.1111/jgh.12073.
PubMed 23216550Willing B, Halfvarson J, Dicksved J, Rosenquist M, Jarnerot G, Engstrand L, Tysk C, Jansson JK. Twin studies reveal specific imbalances in the mucosa-associated microbiota of patients with ileal Crohn's disease. Inflamm Bowel Dis. 2009 May;15(5):653-60. doi: 10.1002/ibd.20783.
PubMed 19023901Sokol H, Seksik P, Furet JP, Firmesse O, Nion-Larmurier I, Beaugerie L, Cosnes J, Corthier G, Marteau P, Dore J. Low counts of Faecalibacterium prausnitzii in colitis microbiota. Inflamm Bowel Dis. 2009 Aug;15(8):1183-9. doi: 10.1002/ibd.20903.
PubMed 19235886Miquel S, Martin R, Rossi O, Bermudez-Humaran LG, Chatel JM, Sokol H, Thomas M, Wells JM, Langella P. Faecalibacterium prausnitzii and human intestinal health. Curr Opin Microbiol. 2013 Jun;16(3):255-61. doi: 10.1016/j.mib.2013.06.003. Epub 2013 Jul 3.
PubMed 23831042Louis P, Flint HJ. Diversity, metabolism and microbial ecology of butyrate-producing bacteria from the human large intestine. FEMS Microbiol Lett. 2009 May;294(1):1-8. doi: 10.1111/j.1574-6968.2009.01514.x. Epub 2009 Feb 13.
PubMed 19222573Khan MT, Duncan SH, Stams AJ, van Dijl JM, Flint HJ, Harmsen HJ. The gut anaerobe Faecalibacterium prausnitzii uses an extracellular electron shuttle to grow at oxic-anoxic interphases. ISME J. 2012 Aug;6(8):1578-85. doi: 10.1038/ismej.2012.5. Epub 2012 Feb 23.
PubMed 22357539Swidsinski A, Loening-Baucke V, Vaneechoutte M, Doerffel Y. Active Crohn's disease and ulcerative colitis can be specifically diagnosed and monitored based on the biostructure of the fecal flora. Inflamm Bowel Dis. 2008 Feb;14(2):147-61. doi: 10.1002/ibd.20330.
PubMed 18050295Plomp N, Gacesa R, Slager J, Samsom JN, Faber KN, Jonkers IH, Withoff S, Wijmenga C, Weersma RK, Harmsen HJM. Synergy between culturomics and metagenomics of health status-associated gut bacteria originating from non-IBD and IBD populations. Sci Rep. 2025 Nov 27;15(1):45469. doi: 10.1038/s41598-025-29138-4.
PubMed 41310063
Study at a glance
From the registry record, last updated by the sponsor on 3 Apr 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Riboflavin Supplementation on Faecalibacterium Prausnitzii in Crohn's Disease
- ClinicalTrials.gov ID
- NCT02538354
- Acronym / sponsor ID
- RISE-UP / METc 2014/291
- Conditions
- Crohn Disease
- Keywords
- Riboflavin (vitamin B2), Faecalibacterium prausnitzii
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 70 participants (actual)
- Lead sponsor
- University Medical Center GroningenUniversity, hospital or other
- Study start
- Mar 2016 (actual)
- Primary completion
- Apr 2017 (actual)
- Study completion
- Apr 2017 (actual)
- First posted
- 2 Sep 2015 (estimated)
- Results
- Posted 3 Apr 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will evaluate if suppelementation of the diet with riboflavin in Crohn's disease patients will result in an increase in the amount of F. prausnitzii.
Detailed description
Rationale Recent studies show that in patients with Inflammatory Bowel Disease (IBD) a dysbiosis exists in the composition of the intestinal microbiota. In particular, the potentially pathogenic bacterium Escherichia coli (E. coli) is often more abundant in the bowel of IBD patients, and the anaerobic commensal Faecalibacterium prausnitzii (F. prausnitzii) is often reduced. This last mentioned bacteria is known to be abundant in the intestine of healthy individuals. It is known to produce butyrate, which stimulates the intestinal epithelium, and to secrete anti-inflammatory substances.
Riboflavin - also known as vitamin B2 - is required for a wide variety of cellular processes and has an important role in maintaining health in humans. In a pilot intervention with healthy volunteers it is shown that a riboflavin supplement increases the number of F. prausnitzii and results in a higher production of butyrate. In Crohn's disease patients, it is known that the amount of F. prausnitzii in the intestine is generally low. Furthermore, it is known that there is an association between the number of F. prausnitzii bacteria and the length of disease in remission.
This study will evaluate if supplementation of the diet with riboflavin in Crohn's disease patients will result in a similar increase in the amount of F. prausnitzii as in healthy volunteers. In this patient group, an increase in the number of F. prausnitzii bacteria in the bowel may result in a more favourable disease course. This will be assessed with faeces calprotectin and two questionnaires. Additionally the investigators will assess if there is any modulation by riboflavin on the other intestinal bacteria, short chain fatty acids (SCFAs) (such as butyrate), and the pH of the faeces. Finally, the effect of the riboflavin on the permeability of the gut will be evaluated with a Chroom-EDTA test, and a number of different biomarkers of permeability.
Hypothesis The hypothesis is that in Crohn's disease patients, supplementation of the diet with riboflavin results in an increase in the amount of F. prausnitzii, changes in microbial composition, increased fatty acid production, an increase in pH and a reduction of intestinal permeability. These changes might result in a more favourable disease course with less exacerbations.
Study design Prospective clinical study.
Study population and sample size In total 84 Crohn's disease patients will be included in this study, divided into two groups. Group 1 (n=42) will consist of patients with disease in remission (quiescent disease); group 2 (n=42) will consist of patients with active disease. In this study an adaptive design will be used. First 12 patients in the disease in remission group will be analysed. The methods of analysis and safety aspects will be taken into account.
Intervention Supplementation of the normal diet with 1 capsule of 100 mg riboflavin (vitamin B2) during three weeks.
Study design
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Riboflavin supplementation in quiescent disease | Experimental | Dietary Supplement: Riboflavin supplementationGroup 1 (n=42) will consist of patients with disease in remission (quiescent disease). |
| Riboflavin supplementation in active disease | Experimental | Dietary Supplement: Riboflavin supplementationGroup 2 (n=42) will consist of patients with active disease. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Crohn's disease patients
- Age 18-65 years
- Concomitant medication for Crohn's disease is allowed in all groups
Key exclusion criteria (7 listed)
- Swallowing disorders
- Pregnancy and lactation
- Use of antibiotic drugs, probiotics (i.e.Yakult, Vifit, Activia etc) or specific prebiotic supplements in the 3 weeks prior to the riboflavin intervention
- Use of Methotrexate drugs
- Colonoscopy and colon cleansing in last 3 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 supplementationAlso: vitamin B2 supplementationSupplementation of the normal diet with 1 capsule of 100 mg riboflavin (vitamin B2) during three weeks | Dietary supplement | Riboflavin supplementation in active disease, Riboflavin supplementation in quiescent disease |
Primary outcome
F. Prausnitzii (FISH Analysis).
Time frame: Different time points up to 6 weeks from start study: Day0, Day7, Day28
The faeces is collected at different time points before and after riboflavin supplementation. To investigate the effect of a riboflavin supplement on the number of F. prausnitzii bacteria in the faeces of active and quiescent Crohn's disease patients.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Apr 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 18242222Sartor RB. Microbial influences in inflammatory bowel diseases. Gastroenterology. 2008 Feb;134(2):577-94. doi: 10.1053/j.gastro.2007.11.059.
- Background: PubMed 18936492Sokol H, Pigneur B, Watterlot L, Lakhdari O, Bermudez-Humaran LG, Gratadoux JJ, Blugeon S, Bridonneau C, Furet JP, Corthier G, Grangette C, Vasquez N, Pochart P, Trugnan G, Thomas G, Blottiere HM, Dore J, Marteau P, Seksik P, Langella P. Faecalibacterium prausnitzii is an anti-inflammatory commensal bacterium identified by gut microbiota analysis of Crohn disease patients. Proc Natl Acad Sci U S A. 2008 Oct 28;105(43):16731-6. doi: 10.1073/pnas.0804812105. Epub 2008 Oct 20.
- Background: PubMed 23216550Fujimoto T, Imaeda H, Takahashi K, Kasumi E, Bamba S, Fujiyama Y, Andoh A. Decreased abundance of Faecalibacterium prausnitzii in the gut microbiota of Crohn's disease. J Gastroenterol Hepatol. 2013 Apr;28(4):613-9. doi: 10.1111/jgh.12073.
- Background: PubMed 19023901Willing B, Halfvarson J, Dicksved J, Rosenquist M, Jarnerot G, Engstrand L, Tysk C, Jansson JK. Twin studies reveal specific imbalances in the mucosa-associated microbiota of patients with ileal Crohn's disease. Inflamm Bowel Dis. 2009 May;15(5):653-60. doi: 10.1002/ibd.20783.
- Background: PubMed 19235886Sokol H, Seksik P, Furet JP, Firmesse O, Nion-Larmurier I, Beaugerie L, Cosnes J, Corthier G, Marteau P, Dore J. Low counts of Faecalibacterium prausnitzii in colitis microbiota. Inflamm Bowel Dis. 2009 Aug;15(8):1183-9. doi: 10.1002/ibd.20903.
- Background: PubMed 23831042Miquel S, Martin R, Rossi O, Bermudez-Humaran LG, Chatel JM, Sokol H, Thomas M, Wells JM, Langella P. Faecalibacterium prausnitzii and human intestinal health. Curr Opin Microbiol. 2013 Jun;16(3):255-61. doi: 10.1016/j.mib.2013.06.003. Epub 2013 Jul 3.
- Background: PubMed 19222573Louis P, Flint HJ. Diversity, metabolism and microbial ecology of butyrate-producing bacteria from the human large intestine. FEMS Microbiol Lett. 2009 May;294(1):1-8. doi: 10.1111/j.1574-6968.2009.01514.x. Epub 2009 Feb 13.
- Background: PubMed 22357539Khan MT, Duncan SH, Stams AJ, van Dijl JM, Flint HJ, Harmsen HJ. The gut anaerobe Faecalibacterium prausnitzii uses an extracellular electron shuttle to grow at oxic-anoxic interphases. ISME J. 2012 Aug;6(8):1578-85. doi: 10.1038/ismej.2012.5. Epub 2012 Feb 23.
- Background: PubMed 18050295Swidsinski A, Loening-Baucke V, Vaneechoutte M, Doerffel Y. Active Crohn's disease and ulcerative colitis can be specifically diagnosed and monitored based on the biostructure of the fecal flora. Inflamm Bowel Dis. 2008 Feb;14(2):147-61. doi: 10.1002/ibd.20330.
- Derived from this study: PubMed 41310063Plomp N, Gacesa R, Slager J, Samsom JN, Faber KN, Jonkers IH, Withoff S, Wijmenga C, Weersma RK, Harmsen HJM. Synergy between culturomics and metagenomics of health status-associated gut bacteria originating from non-IBD and IBD populations. Sci Rep. 2025 Nov 27;15(1):45469. doi: 10.1038/s41598-025-29138-4.
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Riboflavin supplementation in people with Crohn Disease, run by University Medical Center Groningen 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 3 inclusion and 7 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 3 Apr 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 3 Apr 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
F. Prausnitzii (FISH Analysis). (time frame: Different time points up to 6 weeks from start study: Day0, Day7, Day28). 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 NCT02538354, which also lists 10 linked publications.
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 3 Apr 2020.