Investigation of the Faecal Loss of Vedolizumab and Its Role in Influencing Serum Drug Levels, Outcomes and Response in Ulcerative Colitis
- Conditions
- Ulcerative Colitis
- Interventions
- Biological: Vedolizumab
- Registration Number
- NCT04006080
- Lead Sponsor
- Guy's and St Thomas' NHS Foundation Trust
- Brief Summary
The purpose of this study is to study the loss of vedolizumab in stool in patients with active ulcerative colitis (UC).
Patients with moderate-to-severe UC who are commencing induction therapy with vedolizumab will be enrolled into a prospective study and stool will be collected for faecal vedolizumab measurement at days 1, 4 and 7; and again at weeks 2, 6 and 14. They will also be evaluated at three time-points (weeks 2, 6 and 14) for clinical and biochemical UC disease activity as well as serum vedolizumab concentrations and anti-vedolizumab antibodies.
- Detailed Description
Primary objective
- To determine whether vedolizumab is present in significant quantities in the stool of patients receiving induction therapy with vedolizumab for active UC.
Secondary objective (s)
* To evaluate whether the presence and quantity of vedolizumab in stool can be used to predict primary non-response to vedolizumab.
* To explore whether a correlation exists between stool vedolizumab concentrations, serum vedolizumab concentrations and UC disease activity and extent.
* To determine whether there is a correlation between stool and serum vedolizumab levels and trafficking of Th1/Th17 effector memory CD4+ T-cells (the key pathogenic subset in IBD) to the colon in UC.
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 30
-
Aged 18 years or over, either male or female
-
Moderate-to-severe UC, defined as:
- SCCAI > 5 and, i. A raised fecal calprotectin (> 59 μg/g) or, ii. A raised CRP (> 5 mg/L) or, iii. Endoscopic disease activity Mayo 2 or above, Evaluated within 6 weeks of study enrollment
-
Commencing vedolizumab treatment
-
Sufficient English language skills to understand the patient information sheet and consent form
- Contra-indication to vedolizumab (i.e. known serious or severe hypersensitivity reaction to vedolizumab or any of its excipients)
- Imminent need for colectomy (i.e. colectomy is being planned)
- Previous ileoanal pouch formation
- Active severe infections such as tuberculosis, sepsis, cytomegalovirus, listeriosis, and opportunistic infections
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Vedolizumab Vedolizumab -
- Primary Outcome Measures
Name Time Method Change in vedolizumab concentrations in stool Days 1, 4 and 7; and weeks 2, 6 and 14 Evaluated using an enzyme-linked immunosorbent assay (ELISA)
- Secondary Outcome Measures
Name Time Method Vedolizumab serum concentrations Weeks 2, 6 and 14 Evaluated using a drug-sensitive enzyme-linked immunosorbent assay (ELISA)
Serum CRP (mg/L) Day 0, weeks 2, 6 and 14 UC histological activity Day 0 and week 14 Evaluated using Nancy Histological Index
Faecal calprotectin Day 0, weeks 2, 6 and 14 Evaluated using a drug-sensitive enzyme-linked immunosorbent assay (ELISA)
Quality of life questionnaire Day 0, weeks 2, 6 and 14 IBD-Control questionnaire
UC endoscopic activity Baseline and week 14 Evaluated using the Ulcerative Colitis Endoscopic Index of Severity (UCEIS) score: Vascular pattern= Normal (0), patchy loss (1), obliterated (2); Bleeding = None (0), mucosal (1), luminal mild (2), luminal moderate (3); Erosions/ulcers = None (0), erosions (1), superfical ulcer (2), deep ulcer (3)
Clinical UC disease activity Day 0, weeks 2, 6 and 14 Evaluated using the Simple Clinical Colitis Activity Index score: Bowel frequency day= 0-3 (0), 4-6 (1), 7-9 (2), \>9 (3); Bowel frequency night= 0 (0), 1-3 (1), 4-6 (2); Urgency of defectation= None(0), Hurry (1), immediately (2), incontinence (3); Blood in stool = None (0), trace (1), occasional frank (2), usually frank (3); General well being= very well (0), slightly below par (1), poor (2), very poor (3), terrible (4); Extracolonic features (1 point for each) = arthritis, uveitis, erythema nodosum, pyoderma gangrenosum. Remission SCCAI ≤ 2; Response SCCAI ≤ 5, with a decrease by ≥ 2; Relapse SCCAI ≥ 5 (following a response)
Vedolizumab anti-drug antibody levels Weeks 2, 6 and 14 Evaluated using a drug-sensitive enzyme-linked immunosorbent assay (ELISA)
Serum albumin (g/L) [40-52g/L] Day 0, weeks 2, 6 and 14
Trial Locations
- Locations (1)
Guy's and St Thomas' NHS Foundation Trust
🇬🇧London, United Kingdom