The Effect of Riboflavin in Crohn's Disease

Crohn Disease Clinical Trial

— RISE-UP  

Official title:

The Effect of Riboflavin Supplementation on Faecalibacterium Prausnitzii in Crohn's Disease

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02538354
• Other study ID #: METc 2014/291
• Secondary ID: Protocol ID
• Status: Completed
• Phase: N/A
• Start date: March 2016
• Est. completion date: April 2017

Study information

• Verified date: March 2020
• Source: University Medical Center Groningen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 70
• Est. completion date: April 2017
• Est. primary completion date: April 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• Crohn's disease patients

• Age 18-65 years

• Concomitant medication for Crohn's disease is allowed in all groups

Exclusion Criteria:

• 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)

Related Conditions & MeSH terms

• Crohn Disease

Intervention

Dietary Supplement:
• Riboflavin supplementation
Supplementation of the normal diet with 1 capsule of 100 mg riboflavin (vitamin B2) during three weeks

Locations

Country	Name	City	State
Netherlands	University Medical Center Groningen	Groningen

Sponsors (1)

Lead Sponsor	Collaborator
University Medical Center Groningen

Country where clinical trial is conducted

Netherlands, 

References & Publications (9)

Fujimoto 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. — View Citation

Khan 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. — View Citation

Louis 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. Review. — View Citation

Miquel S, Martín R, Rossi O, Bermúdez-Humarán 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. Review. — View Citation

Sartor RB. Microbial influences in inflammatory bowel diseases. Gastroenterology. 2008 Feb;134(2):577-94. doi: 10.1053/j.gastro.2007.11.059. Review. — View Citation

Sokol H, Pigneur B, Watterlot L, Lakhdari O, Bermúdez-Humarán LG, Gratadoux JJ, Blugeon S, Bridonneau C, Furet JP, Corthier G, Grangette C, Vasquez N, Pochart P, Trugnan G, Thomas G, Blottière HM, Doré 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. — View Citation

Sokol H, Seksik P, Furet JP, Firmesse O, Nion-Larmurier I, Beaugerie L, Cosnes J, Corthier G, Marteau P, Doré J. Low counts of Faecalibacterium prausnitzii in colitis microbiota. Inflamm Bowel Dis. 2009 Aug;15(8):1183-9. doi: 10.1002/ibd.20903. — View Citation

Swidsinski 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. — View Citation

Willing B, Halfvarson J, Dicksved J, Rosenquist M, Järnerot 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Different time points up to 6 weeks from start study: Day0, Day7, Day28