Local and Systemic Immunoprofiling of Patients Diagnosed With Ulcerative Colitis

Ulcerative Colitis Flare Clinical Trial

— ImmUniverse  

Official title:

Better Control and Treatment of Ulcerative Colitis by Exploring the Universe of Microenvironment Imposed Tissue Signatures and Their Correlates in Liquid Biopsies

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05680883
• Other study ID #: NL78552.091.21
• Status: Recruiting
• Start date: May 5, 2022
• Est. completion date: November 5, 2023

Study information

• Verified date: November 2022
• Source: Radboud University Medical Center
• Contact: Hans Koenen
• Phone: +31 243693478
• Email: Hans.Koenen[@]radboudumc.nl
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Immune-mediated diseases are extremely diverse - patients with the same diagnosis may see the disease progress in very different ways, and respond differently to treatments. This is because the course of the disease is influenced by multiple factors, including the patient's genes, immune system, environment, and the microbes living in their gut. Furthermore, all of these factors interact with and impact on one another. As a result, it is very hard to predict how the disease will develop in a specific patient, and which treatments will be effective. Hence, mechanistic understanding of this heterogeneity and biomarkers predictive for disease control and therapy response over time are important prerequisites of a future precision medicine in IMIDs. ImmUniverse has been formed as a European transdisciplinary consortium to tackle these unmet needs and to understand the role of the crosstalk between tissue microenvironment and immune cells in disease progression and response to therapy of ulcerative colitis (UC) and atopic dermatitis (AD).

The consortium will combine analysis of tissue-derived signatures with "circulating signatures" detectable in liquid biopsies, employing state-of-the-art profiling technologies to provide new validated diagnostics in IMID that are expected to improve patient management, lead to increased patient well-being and will significantly reduce the socioeconomic burden of these diseases. This study, being Immuniverse work package 5 (WP5), will verify the disease pathway -and mechanism signatures identified in the multi omic discovery WP2 in immune cells in affected tissue and peripheral blood. WP5 aims to further substantiate our understanding of the immune-mediated intestinal disease ulcerative colitis (UC). It will use liquid biopsies (peripheral blood) and affected UC gut inflamed and non-inflamed biopsies to generate transcriptome, proteome, DNA-methylome and miRNA signatures of immune cell subsets and analyse the association between immune cells circulating in peripheral blood and the microenvironment of affected colonic tissue.

Also this WP aims to develop a protocol to analyse and sort living immune cells from cryopreserved tissue. Ultimately, the project's findings should contribute to a better, more precise diagnosis for patients; and better information on how severe the disease is likely to be for each individual patient and how it will progress over time. Finally, the project will make it easier for doctors and patients to monitor how well a treatment is working in the future.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: November 5, 2023
• Est. primary completion date: November 5, 2023
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Diagnosis of Ulcerative Colitis

• Age = 18 years

• Present in the hospital for a regular outpatient visit

• Willing and able to comply with the study related procedures

• Provide signed informed consent

Exclusion Criteria:

• Age = 18 years

• Unable to give informed consent

• Unable or unwilling to comply with study-related procedures

• Crohn's Disease or IBD undiagnosed

Related Conditions & MeSH terms

• Colitis
• Colitis, Ulcerative
• Ulcer
• Ulcerative Colitis Flare

Locations

Country	Name	City	State
Netherlands	RadboudUMC	Nijmegen	Gelderland

Sponsors (1)

Lead Sponsor	Collaborator
Radboud University Medical Center

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Comparing immune cells in blood, inflamed and uninflamed colonic biopsies by means of flow cytometry	Assessed by differences in Mean Fluorescent Intensity in whole blood sampels vs. inflamed and uninflamed biopsies	Through study completion, an average of 1.5 years
Primary	Comparing immune cells in blood, inflamed and uninflamed colonic biopsies by means of flow cytometry	Assessed by differences in percentages of cell populations in whole blood sampels vs. inflamed and uninflamed biopsies	Through study completion, an average of 1.5 years
Primary	Comparing gene expression profiles in blood, inflamed and uninflamed colonic biopsies	Assessment of mean expression of genes in blood vs. inflamed and uninflamed biopsies by means of single cell RNA sequencing	Through study completion, an average of 1.5 years
Primary	Localizing immune cells of interest of inflamed and uninflamed biopsies	By using immunohistochemistry: quantified by cells per field	Through study completion, an average of 1.5 years
Secondary	For 40 patients: height	Height in centimeter, combined with weight to get to BMI (kg/m^2)	Through study completion, an average of 1.5 years
Secondary	For 40 patients: weight	Weight in kilograms, combined with height to get to BMI (kg/m^2)	Through study completion, an average of 1.5 years
Secondary	For 40 patients: smoking status	Current/active smoker; Previous smoker; Never smoked; Not described	Through study completion, an average of 1.5 years
Secondary	For 40 patients: montreal classification	E1: ulcerative proctitis; E2: left-sided UC (distal to splenic flexure); E3: Entensive UC (pancolitis)	Through study completion, an average of 1.5 years
Secondary	For 40 patients: SCCAI-score	Based on 6 variables: Bowel frequency (day); Bowel frequency (night); Urgency of defecation; Blood in stool; General well-being; Extracolonic features	Through study completion, an average of 1.5 years
Secondary	For 40 patients: Mayo score (based on physician rating of endoscopic disease activity)	0: normal or inactive disease; 1: mild disease (erythema, decreased vascular pattern, mild friability) 2. Moderate disease (marked erythema, absent vascular pattern, friability, erosions) 3. Severe disease (spontaneous bleeding, ulcerations)	Through study completion, an average of 1.5 years
Secondary	For 40 patients: Medication history and current medication	anti-TNF, Vedolizumab, Janus kinase inhibitors, thiopurine, methotrexate, aminosalicylates, corticosteroids (grams of medication/day)	Through study completion, an average of 1.5 years
Secondary	For 40 patients: Feacel calprotectin	mg/kg feces	Through study completion, an average of 1.5 years
Secondary	For 40 patients: Albumin	g/L	Through study completion, an average of 1.5 years
Secondary	For 40 patients: infections in stool	yes/no	Through study completion, an average of 1.5 years
Secondary	Blood parameters	WBC count (*10^9/L), RBC count (*10^12/L), PLT (*10^9/L), Lymphocytes (*10^9/L), Monocytes (*10^9/L), Neutrophils (*10^9/L), Eosinophils (*10^9/L), Basiphils (*10^9/L)	Through study completion, an average of 1.5 years