Ulcerative Colitis
Conditions
Brief summary
An imbalance in the gut microbiota and mucosal immune dysfunction leading to intestinal inflammation are central to the pathogenesis of ulcerative colitis (UC). Both international and domestic inflammatory bowel disease (IBD) guidelines consistently recommend the use of the probiotic VSL#3 for inducing or maintaining remission in cases of mild-to-moderate UC. While the development of biologic therapies in recent years has provided new directions for IBD treatment, classic biologics such as infliximab may increase the risk of opportunistic infections and malignancies. Vedolizumab, when used for the induction therapy of UC, has a response rate of less than 80%, a slightly slower onset of action, and a slight increase in Clostridioides difficile infection (CDI) incidence. Currently, there is a lack of clinical data on the adjunctive use of VSL#3 with biologic agents in the treatment of UC globally. Therefore, this project aims to design a multi-center, randomized, placebo-controlled, double-blind study. The primary objective is to compare the changes in clinical response in patients with moderately active UC treated with either VSL#3 or placebo in combination with vedolizumab (VDZ) for six weeks.
Detailed description
This study enrolled patients aged 18-85 years with moderate ulcerative colitis and randomly assigned them in a 1:1 ratio to an experimental group and a control group. Patients in the experimental group received two packets of VSL#3 (450 billion CFU/packet) daily for 14 weeks, along with Vedolizumab (300 mg once weekly at weeks 0, 2, 6, and 14). The control group received placebo packets and Vedolizumab on the same schedule. The primary outcome was the proportion of patients with a decrease of ≥3 points in the SCCAI score at week 6, along with improvement in fecal calprotectin (FC) levels (decrease of ≥50% from baseline) at weeks 6 and 14. Secondary outcomes included clinical response, clinical remission, corticosteroid-free clinical remission, and changes in quality of life scores at week 14.
Interventions
DIETARY_SUPPLEMENTVSL#3
VSL#3 450 billion CFU/sachet
DIETARY_SUPPLEMENTPlacebo
Placebo sachets with maltose, cornstarch and dioxide
DRUGVedolizumab
Patients will start combined therapy with vedolizumab and VSL#3 or placebo at the same time. Vedolizumab will be administered according to clinical practice with the following schedule: 300 mg intravenously on Baseline (Day 1 / Week 0) and Weeks 2, 6, and 14, with a flexibility of ±3 days relative to the start of VSL#3 administration.
Sponsors
Second Affiliated Hospital, School of Medicine, Zhejiang University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Intervention model description
A Multicenter, Randomized, Double-blind, Placebo-controlled trial in adult subjects with moderate active ulcerative colitis
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* Subject must be a man or woman aged 18-85 years, inclusive. * Diagnosed with ulcerative colitis (UC) at least 90 days prior to baseline, supported by comprehensive colonoscopy findings and histopathological evidence obtained within the past year. Participants must provide full colonoscopy or sigmoidoscopy reports along with pathology results conducted within the last 3 months, as well as blood indicators (within 1 week) at baseline screening. Individuals currently experiencing infection, dysplasia, or malignancy will be excluded from participation. * Subject has moderate active UC and had a Mayo score of 6-10 at screening. * Planned treatment with Vedolizumab as initial therapy or reinduction, with reinduction defined as no vedolizumab treatment within 1 year. * Confirmed by the investigator that despite receiving at least one of the following treatments, the subject has shown an inadequate response, loss of response, or intolerance: 1. Oral aminosalicylates (e.g., mesalamine, sulfasalazine, olsalazine, balsalazide), where the subject exhibits ongoing signs and symptoms of active disease during at least 4 weeks of treatment with mesalamine 2.4 g/day, sulfasalazine 4 g/day, olsalazine 1 g/day, or balsalazide 6.75 g/day. 2. Immunosuppressants: failure to respond after receiving at least 42 consecutive days of treatment with azathioprine, 6-mercaptopurine, or methotrexate (MTX) injections prior to baseline (Week 0), with minimum doses of azathioprine ≥ 0.75 mg/kg/day or 6-MP ≥ 0.5 mg/kg/day (rounded to the nearest tablet dose) or MTX ≥ 15 mg/week (SC/IM), or the highest tolerated dose due to adverse effects such as leukopenia, elevated liver enzymes, or nausea. * No increase in dose of oral 5-ASA and Immunosuppressants could be allowed if it is maintained stable at least 2 weeks before screening. * Subject must be willing and able to adhere to the prohibitions and restrictions specified in this protocol. * Willing and able to complete the required Subject Diary. * Willing and able to meet all study requirements, including attending all assessment visits and phone calls.
Exclusion criteria
* Diagnosis of Crohn's disease, undetermined IBD or other colitis. * UC disease limited to the rectum (\<15 cm from the anal verge) * Steroid therapy initiation within 2 weeks before screening visit. * Used antibiotics for intestinal or other infections within 2 weeks of the screening * Use of other probiotics preparations within the last 2 weeks before study entry (screening) * Used rectal 5-ASA within the past week before study entry (screening) * Adjustment of oral 5-ASA and immunosuppressant dosages due to disease progression after colonoscopy screening until enrollment. * Within 1 week prior to screening, the participant has taken nonsteroidal anti-inflammatory drugs (NSAIDs) or anti-diarrheal medications for 5 consecutive days. * Positive Clostridioides difficile detection toxin results within the past month prior to screening. * Pregnancy and breastfeeding women * Other biologics/advanced therapies are used as concomitant therapy and Previous use of other biologics * History of allergy to maltose and/or cornstarch and/or silica * Subjects with severe primary heart, liver, lung, kidney, hematologic, or serious diseases that affect their survival, such as cancer, AIDS, asthma, kidney stones, renal dysfunction; urine protein \>+, microscopic hematuria, ALT \>2N (N is the upper limit of normal), Cr \> normal upper limit, platelet count \<50x10\^9/L, white blood cell count \<3.0x10\^9/L.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Response rate at week 6 | At week 6 | The proportion of participants with a SCCAI score reduction of ≥3 points from baseline in the experimental group compared to the control group at week 6 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Remission rate at week 14 | At Week 14 | The proportion of participants in the experimental group compared to the control group at week 14 with: * A modified Mayo score ≤2 points and no single item score \>1 point. * Or a PRO2 score with a rating of 0 for rectal bleeding and stool frequency. * Or a SCCAI score ≤2 points. |
| Steroid-free Clinical Remission rate at week 14 | At Week 14 | The proportion of participants in the experimental group compared to the control group at week 14 with a modified Mayo score ≤2 points and no single item score \>1 point, and who have completely tapered off steroids. |
| At week 2 on PRO2 and Urgency NRS through dairy daily | At Week 2 | At Week 2, assess the proportion of participants achieving a decrease in the PRO2 (Patient-Reported Outcome) scores for rectal bleeding and stool frequency, and the mean value of the Urgency Numeric Rating Scale (UNRS) for bowel movements. |
| Clinical Response rate at week 14 | At Week 14 | The proportion of participants in the experimental group compared to the control group at week 14 with: * A reduction in modified Mayo score of ≥30% and ≥3 points from baseline, along with a decrease of ≥1 point in the rectal bleeding subscore or a subscore of 0 or 1. * Or a PRO2 score showing at least a 50% reduction in rectal bleeding and stool frequency. * Or a reduction in SCCAI score of ≥3 points. |
| The proportion of patients with a ≥50% decrease in fecal calprotectin (FC) and the changes in the Urgency Numeric Rating Scale (UNRS) | At the end of treatment weeks 6 and 14 | At Week 14 and Week 6, assess the proportion of participants achieving a decrease in fecal calprotectin (FC) levels of ≥50% from baseline, and the changes in the mean value of the Urgency Numeric Rating Scale (UNRS) from baseline. |
| Adverse Events | Through Week 14 | Compare the incidence of adverse events between the experimental group and the control group at weeks 2, 6, and 14. |
| Inflammatory Bowel Disease Questionnaire (IBDQ) variation | At the end of treatment weeks 6 and 14 | The difference between the IBDQ scores obtained at Week 14 and Week 6, compared to the baseline (initial) IBDQ scores taken before the start of the intervention or treatment. |
Countries
China
Contacts
Primary ContactYan Chen, PhD
Backup ContactQiao Yu, PhD
Outcome results
None listed