A Prospective Longitudinal Study of Fecal Microbiome and Calprotectin to Predict Relapse in Patients With IBD

Ulcerative Colitis Clinical Trial

Official title:

A Prospective Longitudinal Study of Fecal Microbiome and Calprotectin to Predict Relapse in Patients With Inflammatory Bowel Disease

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04079335
• Other study ID #: IBD MiREL
• Status: Recruiting
• Start date: January 28, 2019
• Est. completion date: January 28, 2021

Study information

• Verified date: September 2019
• Source: Chinese University of Hong Kong
• Contact: Jessica Ching
• Phone: +852 35053524
• Email: jessicaching[@]cuhk.edu.hk
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Inflammatory bowel disease (IBD) is a chronic idiopathic inflammatory condition of the intestine, which results in diarrhea, rectal bleeding, urgency, weight loss and abdominal pain. The natural course of IBD is characterized by activity outbreaks and periods of remission. In most cases, relapses in Crohn's disease (CD) and in ulcerative colitis (UC) are unpredictable and despite effective medical treatment, a degree of subclinical inflammation may persist in the bowel wall, contributing to a significant risk of relapse.

In IBD, altered fecal microbiota signatures have been consistently reported which included a reduction in biodiversity with lower proportions of Firmicutes and increases in Proteobacteria and Bacteroidetes phylum members.

It is however unclear whether changes in microbial profile including diversity and composition can predict disease relapse in IBD. We hypothesize that fecal microbial signatures in conjunction with fecal calprotectin may play a role in predicting relapse in IBD patients.

Description:

Inflammatory bowel disease (IBD) is a chronic idiopathic inflammatory condition of the intestine, which results in diarrhea, rectal bleeding, urgency, weight loss and abdominal pain. The natural course of IBD is characterized by activity outbreaks and periods of remission. In most cases, relapses in Crohn's disease (CD) and in ulcerative colitis (UC) are unpredictable and despite effective medical treatment, a degree of subclinical inflammation may persist in the bowel wall, contributing to a significant risk of relapse.

Endoscopy has been used to monitor a disease but it is time-consuming, costly, invasive, and associated with certain risks of morbidity. Many patients are reluctant to undergo repeated endoscopic examinations, particularly when their disease is quiescent. Acute phase reactants have been used but their sensitivity and specificity in correlating to intestinal inflammatory activity are very low, and their capacity to predict disease relapse is poor and controversial. A number of fecal biomarkers have been evaluated for their utility for monitoring and predicting relapse in IBD but some of these biomarkers are also not specific.

In IBD, altered fecal microbiota signatures have been consistently reported which included a reduction in biodiversity with lower proportions of Firmicutes and increases in Proteobacteria and Bacteroidetes phylum members. In addition, disease remission and relapse are associated with microbial changes in both mucosal and fecal samples. In particular, a loss of species richness in Crohn's disease has been widely observed. Recently microbial biomarkers may differentiate between CD and UC. Furthermore, different microbial groups are associated with smoking habit and localization of the disease in CD and UC. It is however unclear whether changes in microbial profile including diversity and composition can predict disease relapse in IBD. We hypothesize that fecal microbial signatures in conjunction with fecal calprotectin may play a role in predicting relapse in IBD patients.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: January 28, 2021
• Est. primary completion date: January 28, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

Patient with Crohn's Disease

1. Aged =18 years old

2. Confirmed diagnosis of ileo-colonic Crohn's disease according to established clinical, endoscopic and histologic criteria

3. History of at least one flare with symptoms that required intervention within 24 months before screening

4. Stable doses of immunosuppressive agents for at least 3 months if these agents are required

5. In clinical remission for at least 3 months, defined as Harvey Bradshaw Index (HBI) score < 4

6. Written informed consent obtained

Patient with Ulcerative Colitis

1. Aged =18 years old

2. Have a confirmed diagnosis of ulcerative colitis according to established clinical, endoscopic and histologic criteria

3. History of at least one flare with symptoms that required intervention within 24 months before screening

4. On stable regimen of 5-ASA for at least 3 months

5. In clinical remission for at least 3 months defined as partial Mayo score = 1

6. Written informed consent obtained

Exclusion Criteria:

1. Previous bowel surgery /stoma

2. On anti-TNF therapy

3. Malignant disease within 5 years

4. Use of probiotics, prebiotics or antibiotics in past 3 months

5. Terminal illness

Related Conditions & MeSH terms

• Colitis, Ulcerative
• Crohn Disease
• Inflammatory Bowel Diseases
• Intestinal Diseases
• Ulcerative Colitis

Locations

Country	Name	City	State
Hong Kong	Chinese University of Hong Kong	Hong Kong

Sponsors (1)

Lead Sponsor	Collaborator
Chinese University of Hong Kong

Country where clinical trial is conducted

Hong Kong, 

References & Publications (6)

D'Haens G, Ferrante M, Vermeire S, Baert F, Noman M, Moortgat L, Geens P, Iwens D, Aerden I, Van Assche G, Van Olmen G, Rutgeerts P. Fecal calprotectin is a surrogate marker for endoscopic lesions in inflammatory bowel disease. Inflamm Bowel Dis. 2012 Dec;18(12):2218-24. doi: 10.1002/ibd.22917. Epub 2012 Feb 16. — View Citation

García-Sánchez V, Iglesias-Flores E, González R, Gisbert JP, Gallardo-Valverde JM, González-Galilea A, Naranjo-Rodríguez A, de Dios-Vega JF, Muntané J, Gómez-Camacho F. Does fecal calprotectin predict relapse in patients with Crohn's disease and ulcerative colitis? J Crohns Colitis. 2010 Jun;4(2):144-52. doi: 10.1016/j.crohns.2009.09.008. Epub 2009 Dec 2. — View Citation

Hanaway P, Roseth A. Inflammatory biomarkers predict relapse in IBD. Gut. 2005 Sep;54(9):1346-7. — View Citation

McIlroy J, Ianiro G, Mukhopadhya I, Hansen R, Hold GL. Review article: the gut microbiome in inflammatory bowel disease-avenues for microbial management. Aliment Pharmacol Ther. 2018 Jan;47(1):26-42. doi: 10.1111/apt.14384. Epub 2017 Oct 16. Review. — View Citation

Pascal V, Pozuelo M, Borruel N, Casellas F, Campos D, Santiago A, Martinez X, Varela E, Sarrabayrouse G, Machiels K, Vermeire S, Sokol H, Guarner F, Manichanh C. A microbial signature for Crohn's disease. Gut. 2017 May;66(5):813-822. doi: 10.1136/gutjnl-2016-313235. Epub 2017 Feb 7. — View Citation

Sartor RB, Wu GD. Roles for Intestinal Bacteria, Viruses, and Fungi in Pathogenesis of Inflammatory Bowel Diseases and Therapeutic Approaches. Gastroenterology. 2017 Feb;152(2):327-339.e4. doi: 10.1053/j.gastro.2016.10.012. Epub 2016 Oct 18. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Clinical relapse for CD patients	Defined as worsening of the symptoms, accompanied by HBI score of = 8 points for CD and require a change in therapy.	2 years
Primary	Clinical relapse for UC patients	Defined as partial Mayo score of = 5 points for UC and require a change in therapy.	2 years