Crohn's Disease of Both Small and Large Intestine
Conditions
Keywords
Stricture
Brief summary
The goal of this observational study is to evaluate the response of guselkumab in adult patients with Crohn's disease (CD) as measured on intestinal ultrasound (IUS), the relative quantities of CD64 in endoscopic tissue biopsies, and the protein signature in the blood of patients with and without therapy response. The main question it aims to answer is: * What is the proportion of ileal Crohn's disease patients with and without strictures who achieve an intestinal ultrasound response? * What is the quantity of CD64 in tissue in CD patients at baseline and at week 52 with and without IUS response? * Are there proteomic signatures in blood of CD patients that respond to GUS?
Detailed description
This is a prospective, single-centre observational study conducted at conducted at the University of Calgary and the University of Alberta. All patients with histologically confirmed distal ileal CD with or without colonic involvement initiating guselkumab (GUS) will be consecutively enrolled. Patients will be sub-divided into the following phenotypes: 1) Stricture: Bowe wall thickness \> 3 mm, luminal apposition \< 1cm and prestenotic dilation of distal ileum, or 2) Non-Stricture (inflammatory): ileal CD with no evidence of stricture on intestinal ultrasound (IUS) or prior cross-sectional imaging. Recruited patients providing informed consent will undergo IUS within 14 days of GUS start with blood collection prior to GUS start. Blood collection and IUS will be performed at weeks 0, 12, 24, and 52. Length of visit windows will be within 14 days of study visit due date. Gastroenterologists with bowel sonography expertise will perform standard of care IUS on all consented CD patients meeting inclusion criteria in clinic at baseline, weeks 12, 24, and 52. Colonoscopy will be performed in all patients at baseline and between week 48 and 52 with segmental biopsies for proteomic and CD64 analysis. For tissue CD64 quantification, a single-cell suspension will be obtained using collagenase type 4 and deoxyribonuclease I for enzymatic digestion followed by mechanical dissociation. CD64 will be tagged using the same markers as described for serum, and samples will be submitted to flow cytometry at the local university facility (Calgary or Alberta). Serum will be collected for proteomic analysis at baseline and week 52.
Interventions
Guselkumab will be prescribed by the patient's primary physician according to approved doses by Health Canada for moderate to severe Crohn's disease. Dosing includes: Induction: 200 mg IV or 400mg sc at Weeks 0, 4, and 8 Maintenance: 100 mg SC every 8 weeks or 200 mg SC every 4 weeks
Sponsors
University of Calgary
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
No minimum to 80 Years
Healthy volunteers
No
Inclusion criteria
Male or female, 18 to 80 years old BWT on IUS \> 3.0mm in the ileum and colonic disease permitted. Patients naïve to guselkumab. Stricture phenotype - BWT \> 3 mm, luminal apposition \< 1cm or \< 50% of adjacent normal bowel diameter, and prestenotic dilation of distal ileum. Naïve or anastomotic strictures permitted. Non-stricture phenotype- ileal CD with no evidence of stricture on IUS, computed tomography enterography (CTE), or magnetic resonance enterography (MRE), ever or fistulizing phenotype.
Exclusion criteria
Pregnancy Ileostomy or colostomy Significant obesity (BMI \> 35) Contraindications to initiating GUS such as active infection. Active malignancy within five years. Conditions with fibrosis involving other organs such as lungs, kidneys, brain, or skin.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of patients with IUS response in patients with and without Crohn's disease strictures on Guselkumab therapy over 1 year | 52 weeks | IUS response: decreased bowel wall thickness of \> 25%, or \> 2.0mm, or \> 1.0mm and one colour Doppler signal reduction. Transmural remission: Bowel wall thickness \< 3mm, colour Doppler signal (modified Limberg grade 0), normal stratification, normal inflammatory fat, and no complications (abscess, phlegmon, fistulas). |
Countries
Canada
Contacts
Primary ContactCathy Lu, MD
Backup ContactMaureen O'Brien
Outcome results
None listed