The Contact Activation System and Ulcerative Colitis

February 24, 2025 updated by: Morten Lee Halling, Esbjerg Hospital - University Hospital of Southern Denmark

The study aims to describe alterations in the contact activation system during active and inactive ulcerative colitis.

Contact activation system measures are compared in a cross sectional (healthy controls vs. active disease) and longitudinal (active diasese vs. inactive disease) fashion.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

We include and follow up on 102 adults with active ulcerative colitis. Visits are week 0 (inclusion), 6, 12 and 26 (end of study). We obtain plasma and fecal samples at each visit. Whereas we obtain colonic tissue samples only at inclusion and end of study.

Registered data are:

  • Demographics realate to UC and general wellbeing.
  • Clinical parametres used for UC evaluation are PRO2, SCCAI, CRP, fecal calprotectin, Mayo endoscopic subscore and Nancy index.
  • The contact activation system is characterised by FXII, prekallikrein, kallikrein generation, HK, cHK (specific to plasma kallikrein), cHK (specific to tissue kallikrein), C1 inhibitor and Kallistatin.
  • Polymerized alpha-1-antitrypsin is characterised by the degree of polymerization and the capacity to activate the contact activation system.

Study Type

Observational

Enrollment (Actual)

102

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Denmark
      • Esbjerg, Denmark, 6700
        • Department of Medical Gastroenterology, University Hospital of Southern Denmark

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Sampling Method

Probability Sample

Study Population

Patients are enrolled from the Department of Medical Gastroenterology at the Hospital of Southwest Jutland, Region of Southern Denmark, Denmark

Description

Inclusion Criteria:

  • Fulfill diagnostic criteria of ulcerative colitis
  • SCCAI score ≥ 5
  • Mayo Endoscopic Subscore ≥ 1
  • Age ≥ 18 years
  • Most understand written and oral information in Danish
  • Informed consent must be given

Exclusion Criteria:

  • Pregnancy
  • Infection at inclusion

  • Any existing disease at inclusion:

    • liver disease or defect in CAS
    • inflammatory rheumatologic or dermatologic disease
    • cardiovascular or renal disease
    • immunodeficiency or hematologic diseases
    • malignancies

  • Medication with

    • Systemic corticosteroids at inclusion
    • ACE-inhibitor
    • Acetylsalicylic acid/NSAID
    • Warfarin, Phenprocoumon, NOAC and heparins

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
UC group
Patients with active ulcerative colitis
Diagnostic test: Continuously assessment of disease activity
Continuous measures of disease activity and activity in the contact activation system.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Clinical disease activity.
Time Frame: End of study (August 28th, 2024)
PRO2 score, 0-6 points. A score of one or more defines active disease.
End of study (August 28th, 2024)
Endoscopic disease activity.
Time Frame: End of study (August 28th, 2024)
Mayo endoscopic score, 0-3 points. A score of one or more defines active disease.
End of study (August 28th, 2024)
Kallikrein generation
Time Frame: End of study (August 28th, 2024)
The assay reflects the downstream activation of the contact activation system which allows us to determine the amount of kallikrein generated in each sample.
End of study (August 28th, 2024)
Polymerised alpha-1-antitrypsin in participants
Time Frame: End of study (August 28th, 2024)
A Western blot verifies the present of polymerised alpha-1-antitrypsin.
End of study (August 28th, 2024)
Polymerised alpha-1-antitrypsin as an activator of the contact activation system
Time Frame: End of study (August 28th, 2024)
We add polymerised alpha-1-antitrypsin to our kallikrein generation. If kallikrein is generated the polymers activated the system.
End of study (August 28th, 2024)
Localisation of contact activation system components in tissue samples
Time Frame: End of study (August 28th, 2024)
Immunhistochemical methods locate FXII, PK, cHK (specific to plasma kallikrein and tissue kallikrein), C1 Inhibitor, and Kallistatin in biopsies.
End of study (August 28th, 2024)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Simple Clinical Colitis Activity Index questionnaire (SCCAI)
Time Frame: 26 weeks
SCCAI score range: 0-21. Score >5 indicate disease activity. The higher score the more disease activity.
26 weeks
Patient Reported Outcome 2 questionnaire (PRO2)
Time Frame: 26 weeks
PRO2 score range: 0-6. The higher score the more disease activity.
26 weeks
Short Inflammatory Bowel Disease Questionnaire (SIBDQ)
Time Frame: 26 weeks
Quality of life assessed in relation to disease activity. Score range: The higher score, the worse quality of life.
26 weeks
Mayo score
Time Frame: 26 weeks
Endoscopic assessment of disease severity. Score range: 0-3. The higher score the worse severity.
26 weeks
Nancy Index
Time Frame: 26 weeks
Histologic assessment of disease severity in colonic biopsies. Score range: Grad 0-4. The higher score the worse severity.
26 weeks
C reactive peptide (CRP)
Time Frame: 26 weeks
The concentration of CRP in plasma.
26 weeks
Calprotectin
Time Frame: 26 weeks
The concentration of calprotectin in stool.
26 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Esbjerg Hospital - University Hospital of Southern Denmark

Collaborators

UMC Utrecht
University of Southern Denmark

Investigators

  • Principal Investigator: Morten L Halling, M.D., Department of Medical Gastroenterology, University Hospital of Southern Denmark - Esbjerg

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 1, 2021

Primary Completion (Actual)

November 30, 2023

Study Completion (Actual)

November 30, 2023

Study Registration Dates

First Submitted

November 3, 2020

First Submitted That Met QC Criteria

November 3, 2020

First Posted (Actual)

November 9, 2020

Study Record Updates

Last Update Posted (Actual)

March 25, 2025

Last Update Submitted That Met QC Criteria

February 24, 2025

Last Verified

February 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CAS UC

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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