The Contact Activation System and Ulcerative Colitis

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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The Contact Activation System and Ulcerative Colitis

Conditions
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Ulcerative Colitis

Intervention / Treatment
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* Diagnostic Test: Continuously assessment of disease activity


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| UC group<br>Patients with active ulcerative colitis | Diagnostic Test: Continuously assessment of disease activity<br>* Continuous measures of disease activity and activity in the contact activation system.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical disease activity. | PRO2 score, 0-6 points. A score of one or more defines active disease. | End of study (August 28th, 2024) | 
| Endoscopic disease activity. | Mayo endoscopic score, 0-3 points. A score of one or more defines active disease. | End of study (August 28th, 2024) | 
| Kallikrein generation | 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 | 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 | 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 | 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) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Misfolded protein, Coagulation Factor XII, Kallikrein, High Molecular Weight Kininogen, The contact activation system, Endoplasmatic reticulum stress, Misfolded alpha-1-antitrypsin, Inflammatory bowel disease, Inflammation