Significance of Ficolin 2 in the Determination of Serological Activity in Chronic Inflammatory Bowel Disease

Crohn Disease Clinical Trial

Official title:

Significance of Ficolin 2 in the Determination of Serological Activity in Chronic Inflammatory Bowel Disease

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01473927
• Other study ID #: 110/06
• Status: Completed
• Phase: N/A
• First received: November 3, 2011
• Last updated: March 11, 2014
• Start date: October 2011
• Est. completion date: June 2013

Study information

• Verified date: March 2014
• Source: University of Bern
• Contact: n/a
• Is FDA regulated: No
• Health authority: Switzerland: Ethikkommission
• Study type: Observational

Clinical Trial Summary

Background Determining disease activity in IBD is sometimes difficult and, to be accurate, requires endoscopy. The serum marker CRP has not proven sufficiently valuable as a marker for IBD specific inflammation. As an alternative, so far fecal calprotectin appears to be more reliable and has shown a certain value as predictive marker. Our preliminary data now show, that the serum concentrations of ficolin-2 are significantly higher in CD patients with a HBI >3. Ficolin-2 is a lectin and acute phase protein produced in the liver and, like MBL, can activate the lectin pathway of complement. Unlike MBL, deficiency for ficolin-2 was not detected in our patient cohort, nor could we find functional deficiencies for ficolin-2 (paper submitted).

Study Aims The study is aimed to substantiate the data from our pilot study which shows that ficolin-2 is significantly increased in CD patients during inflammation. Therefore, the study will measure ficolin-2 concentrations in a sufficiently large patient group to obtain enough statistical power and to compare these results with the endoscopic disease score (SES-CD) and CRP and calprotectin values. Statistical analysis of the data will show us if ficolin-2 is a reliable and easy to obtain new marker for active inflammation in CD.

Study Design Based on a power analysis 112 CD patients and 112 UC patients need to be analyzed. They will be recruited from Bern, Basel and Lausanne. Only patients with routine endoscopy will be included in the study and will be scored by SES-CD. Blood samples will be collected at the day of endoscopy. Stool sample will be collected within the same week of endoscopy. Calprotectin and CRP concentrations will be determined by routine diagnostics, ficolin-2 concentrations will be determined by ELISA in our laboratory. Finally, all data will be statistically analyzed.

Description:

Background

Background Like mannan-binding lectin (MBL), ficolins are important soluble receptors for microbial associated molecular patterns leading to the activation of the lectin pathway complement. Ficolins are structurally related to MBL, but due to their different carbohydrate recognition domain represent an own family of lectins (1). The single polypeptide chains of ficolins form trimers and the trimers finally form higher order structures (tetramers up to hexamers) which constitute the functional protein. Humans have three ficolins: Ficolin-1 (M-ficolin), -2 (L-ficolin) and -3 (H-ficolin), whereas ficolin-2 and -3 are present in the serum, ficolin-1 is found on the surface of monocytes. Both, ficolin-2 and -3 are produced in the liver with an additional source for ficolin-3 in the lung. Like MBL, ficolins have to assemble with the MBL-associated serin proteases (MASPs) in order to activate the complement pathway (1). In our study on a possible role for the influence of the complement system in the development of CD-associated anti-Saccharomyces cerevisiae antibodies (ASCAs), we noticed that chronic inflammatory bowel disease (CIBD) patients, specifically Crohn's disease (CD) patients, exhibited high serum ficolin 2 concentrations.

Our research group is interested in the interaction of the innate immune system with microorganisms of the intestinal flora, focusing on possible defects in innate immune mechanisms. We have more than ten years experience in the field, with a special focus on ASCA and MBL. We have been able to continuously publish our work about these theories.

Our earlier and present studies on the role of MBL and the lectin pathway of complement in CD led to the finding of increased ficolin-2 concentration in the sera of CD patients. Moreover, we found that CD patients with a Harvey-Bradshaw index >3 had significantly higher ficolin 2 concentrations than those with a Harvey-Bradshaw index of ≤ 3.

Study Hypotheses

The following hypotheses are to be tested:

1. The ficolin 2 concentration is higher in Crohn's patients with active disease than in CD patients in remission.

2. Ficolin 2 correlates with endoscopic activity.

3. Ficolin 2 correlates with calprotectin.

Objective

The findings from the first part of the study are to be confirmed in a prospective and more detailed study with a larger patient cohort, testing our (new) working hypothesis that ficolin 2 represents a serum marker for disease activity in CD.

Since it is currently difficult to reliably determine disease activity in CD patients using serum and stool markers without simultaneous endoscopic examination, another specific and easy to obtain disease marker which correlates well with disease activity would be highly welcome. Particularly because the current standard marker, to monitor disease activity (faecal calprotectin), is much less accepted than testing for parameters in the blood.

Therefore, the study aims at answering the question of whether ficolin 2 is present in greater concentrations in the blood of Crohn's patients with active inflammation compared to CD patients in remission or to ulcerative colitis (UC) patients.

Methods

For the purposes of the study, the endoscopic activity index will be recorded using the SES-CD (simplified endoscopic score for CD) for Crohn's patients and the Mayo score for colitis patients.

Approximately 5 ml blood will be taken to prepare serum. (5.5 ml or 4.9 ml S Monovette or 4.7 ml or 4.9 ml serum gel Monovette).

A second test tube of blood will be taken for CRP determination. In order to measure calprotectin, the patient will be asked to provide a stool sample shortly before or shortly after the endoscopic examination (within one week).

Serum ficolin values are measured by enzyme-linked immune sorbent assay (ELISA) in the laboratory at the Department of Clinical Research, University of Bern; all other values are determined in routine diagnostic laboratories.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 136
• Est. completion date: June 2013
• Est. primary completion date: February 2013
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

• known IBD

• endoscopy for clinical reasons

• enrolled in the Swiss IBD cohort study

Exclusion Criteria

Study Design

Observational Model: Case-Only, Time Perspective: Cross-Sectional

Related Conditions & MeSH terms

• Crohn Disease
• Inflammatory Bowel Diseases
• Intestinal Diseases

Intervention

Other:
• Endoscopy
Only patients undergoing endoscopy for clinical reasons will be included in the study, i.e. no endoscopies will be performed solely for study reasons. For the purposes of our study, endoscopy serves to determine the degree of inflammation and no additional biopsies are taken. Blood for CRP and ficolin-2 analysis will be taken through the Venflon® installed for endoscopy.
• Endoscopy
Only patients undergoing endoscopy for clinical reasons will be included in the study, i.e. no endoscopies will be performed solely for study reasons. For the purposes of our study, endoscopy serves to determine the degree of inflammation and no additional biopsies are taken. Blood for CRP and ficolin-2 analysis will be taken through the Venflon® installed for endoscopy.

Locations

Country	Name	City	State
Switzerland	Gastroenterology and Hepatology, Basel University Hospital	Basel	Basel Stadt
Switzerland	DCR, Gastroenterology, Bern, University of Bern	Bern
Switzerland	Service de gastro-entérologie et hépatologie, CHUV Lausanne	Lausanne	Vaud

Sponsors (5)

Lead Sponsor	Collaborator
University of Bern	MSD Merck Sharp & Dohme AG, Swiss IBD Cohort Study, University Hospital, Basel, Switzerland, University of Lausanne Hospitals

Country where clinical trial is conducted

Switzerland, 

References & Publications (1)

Holmskov U, Thiel S, Jensenius JC. Collections and ficolins: humoral lectins of the innate immune defense. Annu Rev Immunol. 2003;21:547-78. Epub 2001 Dec 19. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Ficolin-2 concentration in serum		During endoscopy	No
Secondary	CRP concentration in serum		During endoscopy	No
Secondary	Calprotectin in stool sample		One week before endoscopy up to one week after endoscopy	No