Ulcerative ColitisPhase 4NCT06609447
The Efficacy and Safety of Combining Probiotic VSL#3 With Vedolizumab for the Treatment of Moderate Ulcerative Colitis
A Phase 4 study testing VSL#3 and Vedolizumab in people with Ulcerative Colitis, run by Second Affiliated Hospital, Zhejiang University, School of Medicine at 12 sites in China.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Ulcerative Colitis
- What is being tested?
- VSL#3 and Vedolizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 100 participants
- Where
- 12 sitesChina
- Study dates
- 21 Sep 2024to 31 Dec 2027
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
- 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.
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- 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.
Who cannot join
- 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)
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- 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.
Trial locations and contacts
12 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Yan Chen, PhD contact
12 sites in 1 country
China12 sites, 12 recruiting
- Not yet recruiting
The Seventh Medical Center, PLA General Hospital
Beijing, Beijing Municipality, 100000
Yan Jia, MD, jiayan328@163.com
- Not yet recruiting
West China Hospital of Sichuan University
Chengdu, Sichuan, 610041
Yufang Wang, PhD, Wangyufang04@163.com
- Recruiting
Chongqing General Hospital
Chongqing, Chongqing Municipality, 401147
Hong Guo, PhD, Hguo_CGH2021@163.com
- Not yet recruiting
The Sixth Affiliated Hospital, Sun Yat-sen University
Guangzhou, Guangdong, 510655
Min Zhi, PhD, zhimin@mail.sysu.edu.cn
- Recruiting
Zhejiang Provincial Hospital of Traditional Chinese Medicine
Hangzhou, Zhejiang, 310006
Yihong Fan, MD, yhfansjn@163.com
- Not yet recruiting
2nd Affiliated Hospital, Zhejiang University School of Medicine
Hangzhou, Zhejiang, 310009
Yu Qiao, PhD, yuqiao@zju.edu.cn
- Not yet recruiting
Huzhou City Central Hospital
Huzhou, Zhejiang, 313000
ChunYan Liu, MD
- Not yet recruiting
Jinhua City Central Hospital
Jinhua, Zhejiang, 321000
Qunying Wang
- Not yet recruiting
Quzhou City People's Hospital
Quzhou, Zhejiang, 324000
Quanzhong Ye
- Not yet recruiting
The Second Affiliated Hospital, Wenzhou Medical University
Wenzhou, Zhejiang, 325000
Yi Jiang, MD
- Recruiting
Renmin Hospital of Wuhan University
Wuhan, Hubei, 430060
Ping An, PhD
- Not yet recruiting
The Second Affiliated Hospital of Xi'an Jiaotong University
Xi’an, Shanxi, 710004
Xin Liu, MD, docliuxin@126.com
About this study
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
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.
Read the 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.
- Conditions
- Ulcerative Colitis
- Being tested
- VSL#3, Placebo, Vedolizumab
- Medical subject headings
- Colitis, Ulcerative
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VSL#3Dietary supplement
VSL#3 450 billion CFU/sachet
PlaceboDietary supplement
Also called Placebo (for VSL#3)
Placebo sachets with maltose, cornstarch and dioxide
VedolizumabDrug
Also called Vedolizumab 300 mg Injection
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.
| Study group | Role | What they receive |
|---|---|---|
| VSL#3 combine with Vedolizumab Arm | Experimental | 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. Receives: Dietary Supplement: VSL#3; Drug: Vedolizumab |
| Placebo combine with Vedolizumab Arm | Placebo comparator | 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. Receives: Dietary Supplement: Placebo; Drug: Vedolizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Clinical Response rate 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
Measured: At week 6
Secondary outcomes (7)
Clinical Response rate 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.
Measured: At Week 14
Clinical Remission rate 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.
Measured: At Week 14
Steroid-free Clinical Remission rate 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.
Measured: At Week 14
At week 2 on PRO2 and Urgency NRS through dairy daily
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.
Measured: At Week 2
Inflammatory Bowel Disease Questionnaire (IBDQ) variation
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.
Measured: 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)
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.
Measured: At the end of treatment weeks 6 and 14
Adverse Events
Compare the incidence of adverse events between the experimental group and the control group at weeks 2, 6, and 14.
Measured: Through Week 14
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Sep 2024
- Study start21 Sep 2024 (estimated)
- Primary completion31 Dec 2027 (estimated)
- Study completion31 Dec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Ulcerative ColitisStudies of the same condition, open and under way.
- More trials run by Second Affiliated Hospital, Zhejiang University, School of MedicineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- A Multicenter, Randomized, Double-blind, Placebo-controlled trial in adult subjects with moderate active ulcerative colitis
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06609447
- Sponsor's protocol ID
- 2024-0602
- Status last verified
- Sep 2024
- First submitted
- 22 Sep 2024
- Last updated
- 24 Sep 2024
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Sep 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT06609447
- Acronym / sponsor ID
- 2024-0602
- Conditions
- Ulcerative Colitis
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- Second Affiliated Hospital, Zhejiang University, School of MedicineUniversity, hospital or other
- Study start
- 21 Sep 2024 (estimated)
- Primary completion
- 31 Dec 2027 (estimated)
- Study completion
- 31 Dec 2027 (estimated)
- First posted
- 24 Sep 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
- Model description
- A Multicenter, Randomized, Double-blind, Placebo-controlled trial in adult subjects with moderate active ulcerative colitis
| Arm | Type | Receives |
|---|---|---|
| VSL#3 combine with Vedolizumab Arm | Experimental | Dietary Supplement: VSL#3, Drug: VedolizumabTreatment 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. |
| Placebo combine with Vedolizumab Arm | Placebo comparator | Dietary Supplement: Placebo, Drug: VedolizumabTreatment 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. |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 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:
Key exclusion criteria (13 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| VSL#3VSL#3 450 billion CFU/sachet | Dietary supplement | VSL#3 combine with Vedolizumab Arm |
| PlaceboAlso: Placebo (for VSL#3)Placebo sachets with maltose, cornstarch and dioxide | Dietary supplement | Placebo combine with Vedolizumab Arm |
| VedolizumabAlso: Vedolizumab 300 mg InjectionPatients 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. | Drug | Placebo combine with Vedolizumab Arm, VSL#3 combine with Vedolizumab Arm |
Primary outcome
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
7 secondary outcomes
Clinical Response rate at week 14
Time frame: At Week 14
Clinical Remission rate at week 14
Time frame: At Week 14
Steroid-free Clinical Remission rate at week 14
Time frame: At Week 14
At week 2 on PRO2 and Urgency NRS through dairy daily
Time frame: At Week 2
Inflammatory Bowel Disease Questionnaire (IBDQ) variation
Time frame: 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
Adverse Events
Time frame: Through Week 14
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Sep 2024.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Yan Chen, PhD contact
12 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing VSL#3 and Vedolizumab in people with Ulcerative Colitis, run by Second Affiliated Hospital, Zhejiang University, School of Medicine at 12 sites in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 24 Sep 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 12 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Yan Chen, PhD (chenyan72_72@zju.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Clinical Response rate at week 6 (time frame: At week 6). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Sep 2024.