The Efficacy and Safety of Combining Probiotic VSL#3 With Vedolizumab for the Treatment of Moderate Ulcerative Colitis

September 22, 2024 updated by: Second Affiliated Hospital, School of Medicine, Zhejiang University

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

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Estimated)

100

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • China
    • Beijing
      • Beijing, Beijing, China, 100000
        • Not yet recruiting
        • The Seventh Medical Center, PLA General Hospital
        • Contact:
    • Chongqing
      • Chongqing, Chongqing, China, 401147
    • Guangdong
      • Guangzhou, Guangdong, China, 510655
        • Not yet recruiting
        • The Sixth Affiliated Hospital, Sun Yat-sen University
        • Contact:
    • Hubei
      • Wuhan, Hubei, China, 430060
        • Recruiting
        • Renmin Hospital of Wuhan University
        • Contact:
          • Ping An, PhD
    • Shanxi
      • Xi'an, Shanxi, China, 710004
        • Not yet recruiting
        • The Second Affiliated Hospital of Xi'an Jiaotong University
        • Contact:
    • Sichuan
      • Chengdu, Sichuan, China, 610041
        • Not yet recruiting
        • West China Hospital of Sichuan University
        • Contact:
    • Zhejiang
      • Hangzhou, Zhejiang, China, 310006
        • Recruiting
        • Zhejiang Provincial Hospital of Traditional Chinese Medicine
        • Contact:
      • Hangzhou, Zhejiang, China, 310009
        • Not yet recruiting
        • 2nd Affiliated Hospital, Zhejiang University School of Medicine
        • Contact:
      • Huzhou, Zhejiang, China, 313000
        • Not yet recruiting
        • Huzhou City Central Hospital
        • Contact:
          • ChunYan Liu, MD
      • Jinhua, Zhejiang, China, 321000
        • Not yet recruiting
        • Jinhua City Central Hospital
        • Contact:
          • Qunying Wang
      • Quzhou, Zhejiang, China, 324000
        • Not yet recruiting
        • Quzhou City People's Hospital
        • Contact:
          • Quanzhong Ye
      • Wenzhou, Zhejiang, China, 325000
        • Not yet recruiting
        • The Second Affiliated Hospital, Wenzhou Medical University
        • Contact:
          • Yi Jiang, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: VSL#3 combine with Vedolizumab Arm

Treatment with probiotic VSL#3 combined with vedolizumab; Subjects will receive two sachets daily of VSL#3, each containing 450 billion bacteria (totaling 900 billion bacteria per day), for 14 weeks.

Vedolizumab will be administere as per clinical practice with the following schedule: 300 mg ev at 0, 2 and 6, 14 weeks.
Dietary supplement: VSL#3
VSL#3 450 billion CFU/sachet
Drug: Vedolizumab
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.
Other Names:
  • Vedolizumab 300 mg Injection
Placebo Comparator: Placebo combine with Vedolizumab Arm
Treatment with placebo combined with vedolizumab; Subjects will receive two sachets daily of Placebo for 14 weeks. Vedolizumab will be administere as per clinical practice with the following schedule: 300 mg ev at 0, 2 and 6, 14 weeks.
Dietary supplement: Placebo
Placebo sachets with maltose, cornstarch and dioxide
Other Names:
  • Placebo (for VSL#3)
Drug: Vedolizumab
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.
Other Names:
  • Vedolizumab 300 mg Injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Clinical Response rate at week 6
Time Frame: 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
At week 6

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Clinical Response rate at week 14
Time Frame: 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.
At Week 14
Clinical Remission rate at week 14
Time Frame: 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.
At Week 14
Steroid-free Clinical Remission rate at week 14
Time Frame: 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 14
At week 2 on PRO2 and Urgency NRS through dairy daily
Time Frame: 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.
At Week 2
Inflammatory Bowel Disease Questionnaire (IBDQ) variation
Time Frame: 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.
At the end of treatment weeks 6 and 14
The proportion of patients with a ≥50% decrease in fecal calprotectin (FC) and the changes in the Urgency Numeric Rating Scale (UNRS)
Time Frame: 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.
At the end of treatment weeks 6 and 14
Adverse Events
Time Frame: Through Week 14
Compare the incidence of adverse events between the experimental group and the control group at weeks 2, 6, and 14.
Through Week 14

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Second Affiliated Hospital, School of Medicine, Zhejiang University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

September 21, 2024

Primary Completion (Estimated)

December 31, 2027

Study Completion (Estimated)

December 31, 2027

Study Registration Dates

First Submitted

September 22, 2024

First Submitted That Met QC Criteria

September 22, 2024

First Posted (Actual)

September 24, 2024

Study Record Updates

Last Update Posted (Actual)

September 24, 2024

Last Update Submitted That Met QC Criteria

September 22, 2024

Last Verified

September 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2024-0602

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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