Clinical trial NCT04621006: The Contact Activation System and Ulcerative Colitis
Official title: The Contact Activation System and Ulcerative Colitis
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Ulcerative Colitis
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
Lead sponsor: Esbjerg Hospital - University Hospital of Southern Denmark
Sponsor class: OTHER
Collaborators: name: UMC Utrecht
name: University of Southern Denmark
First posted: 2020-11-09
Enrollment: 102
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
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

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.

Eligibility criteria: 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

Primary outcomes:
measure: Clinical disease activity.
timeFrame: End of study (August 28th, 2024)
measure: Endoscopic disease activity.
timeFrame: End of study (August 28th, 2024)
measure: Kallikrein generation
timeFrame: End of study (August 28th, 2024)
measure: Polymerised alpha-1-antitrypsin in participants
timeFrame: End of study (August 28th, 2024)
measure: Polymerised alpha-1-antitrypsin as an activator of the contact activation system
timeFrame: End of study (August 28th, 2024)
measure: Localisation of contact activation system components in tissue samples
timeFrame: End of study (August 28th, 2024)
Secondary outcomes:
Other outcomes:
Locations:
city: Esbjerg
country: Denmark
facility: Department of Medical Gastroenterology, University Hospital of Southern Denmark
Study officials:
affiliation: Department of Medical Gastroenterology, University Hospital of Southern Denmark - Esbjerg
name: Morten L Halling, M.D.
role: PRINCIPAL_INVESTIGATOR
References: