Ulcerative Colitis
Conditions
Keywords
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
Brief summary
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
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.
Interventions
DIAGNOSTIC_TESTContinuously assessment of disease activity
Continuous measures of disease activity and activity in the contact activation system.
Sponsors
UMC Utrecht
University of Southern Denmark
Esbjerg Hospital - University Hospital of Southern Denmark
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinical disease activity. | End of study (August 28th, 2024) | PRO2 score, 0-6 points. A score of one or more defines active disease. |
| Endoscopic disease activity. | End of study (August 28th, 2024) | Mayo endoscopic score, 0-3 points. A score of one or more defines active disease. |
| Kallikrein generation | 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. |
| Polymerised alpha-1-antitrypsin in participants | End of study (August 28th, 2024) | A Western blot verifies the present of polymerised alpha-1-antitrypsin. |
| Polymerised alpha-1-antitrypsin as an activator of the contact activation system | 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. |
| Localisation of contact activation system components in tissue samples | 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. |
Countries
Denmark
Outcome results
None listed