Clinical trial NCT06609447: The Efficacy and Safety of Combining Probiotic VSL#3 With Vedolizumab for the Treatment of Moderate Ulcerative Colitis
Official title: A Multicenter Randomized, Double-blind, Placebo-controlled Study on the Efficacy and Safety of Combining Probiotic VSL#3 With Vedolizumab for the Treatment of Moderate Ulcerative Colitis
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Ulcerative Colitis
Lead sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University
Sponsor class: OTHER
First posted: 2024-09-24
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: A Multicenter, Randomized, Double-blind, Placebo-controlled trial in adult subjects with moderate active ulcerative colitis
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Clinical Response rate at week 6
timeFrame: At week 6
Secondary outcomes:
measure: Clinical Response rate at week 14
timeFrame: At Week 14
measure: Clinical Remission rate at week 14
timeFrame: At Week 14
measure: Steroid-free Clinical Remission rate at week 14
timeFrame: At Week 14
measure: At week 2 on PRO2 and Urgency NRS through dairy daily
timeFrame: At Week 2
measure: Inflammatory Bowel Disease Questionnaire (IBDQ) variation
timeFrame: At the end of treatment weeks 6 and 14
measure: The proportion of patients with a ≥50% decrease in fecal calprotectin (FC) and the changes in the Urgency Numeric Rating Scale (UNRS)
timeFrame: At the end of treatment weeks 6 and 14
measure: Adverse Events
timeFrame: Through Week 14
Other outcomes:
Locations:
city: Beijing
country: China
facility: The Seventh Medical Center, PLA General Hospital
state: Beijing
city: Chongqing
country: China
facility: Chongqing General Hospital
state: Chongqing
city: Guangzhou
country: China
facility: The Sixth Affiliated Hospital, Sun Yat-sen University
state: Guangdong
city: Wuhan
country: China
facility: Renmin Hospital of Wuhan University
state: Hubei
city: Xi'an
country: China
facility: The Second Affiliated Hospital of Xi&#39;an Jiaotong University
state: Shanxi
city: Chengdu
country: China
facility: West China Hospital of Sichuan University
state: Sichuan
city: Hangzhou
country: China
facility: Zhejiang Provincial Hospital of Traditional Chinese Medicine
state: Zhejiang
city: Hangzhou
country: China
facility: 2nd Affiliated Hospital, Zhejiang University School of Medicine
state: Zhejiang
city: Huzhou
country: China
facility: Huzhou City Central Hospital
state: Zhejiang
city: Jinhua
country: China
facility: Jinhua City Central Hospital
state: Zhejiang
city: Quzhou
country: China
facility: Quzhou City People's Hospital
state: Zhejiang
city: Wenzhou
country: China
facility: The Second Affiliated Hospital, Wenzhou Medical University
state: Zhejiang
Study officials:
References: