Probiotics for Ulcerative Colitis

Overseen By Zhi-Dong Jiang, Dr.PH

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: The University of Texas Health Science Center, Houston

Must not be taking: Antibiotics, Immunosuppressants

Disqualifiers: Pregnancy, HIV, Hepatitis, Cancer, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

58 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines the effectiveness of a new probiotic capsule, PRIM-DJ2727, for individuals with ulcerative colitis (UC) in remission. The aim is to determine if these capsules can maintain UC symptom relief and identify any changes in gut bacteria associated with the treatment. Participants will receive either the probiotic or a placebo (a look-alike pill with no active ingredients). This trial suits those who experienced active UC in the past year but are currently in remission and managing their condition with stable treatment. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop your current medications, but it mentions that you should be on stable maintenance therapy for ulcerative colitis. It's best to discuss your specific medications with the study team.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that treatments like PRIM-DJ2727, which use fecal microbiota transplantation (FMT), offer potential benefits for people with ulcerative colitis (UC). Studies indicate that FMT can lead to higher remission rates, meaning symptoms improve or disappear, compared to those who do not receive the treatment.

For safety, the treatment involves taking capsules with healthy gut bacteria, which are generally well-tolerated. Some individuals might experience mild stomach discomfort, but serious side effects are rare. As this study is in an early phase, it continues to gather more detailed safety information. However, reaching this stage suggests that earlier tests did not reveal major safety concerns. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for ulcerative colitis?

Unlike the standard treatments for ulcerative colitis, which typically include anti-inflammatory medications, immunosuppressants, or biologics, PRIM-DJ2727 is unique because it involves fecal microbiota transplantation (FMT) delivered through capsules. This approach uses beneficial bacteria from healthy donors to restore the gut microbiome balance in patients with ulcerative colitis. Researchers are excited about this treatment because it offers a potential new way to manage the condition by addressing the gut's bacterial environment directly, which could lead to improved outcomes and fewer side effects compared to traditional drugs.

What evidence suggests that PRIM-DJ2727 might be an effective treatment for ulcerative colitis?

Research has shown that fecal microbiota transplantation (FMT) can help treat ulcerative colitis (UC). Studies have found that FMT provides better symptom relief and visible healing compared to other treatments for individuals with active UC. In this trial, participants with UC will receive either PRIM-DJ2727, a type of FMT in capsule form, or a placebo to determine if PRIM-DJ2727 helps maintain remission, meaning their symptoms remain controlled. Previous users of similar treatments have reported good results in managing their symptoms. This suggests that PRIM-DJ2727 could help individuals with UC remain symptom-free for longer. ^{1 2 3 4 5}

Are You a Good Fit for This Trial?

Adults over 18 with Ulcerative Colitis in remission can join this trial. They must have had active UC within the last year, be on stable therapy, and agree to use birth control if applicable. Exclusions include other GI conditions, certain infections like HIV or Hepatitis B/C, compromised immune systems, recent FMT or investigational drugs, inability to take oral capsules, pregnancy/breastfeeding intentions during the study.

Inclusion Criteria

I have had active ulcerative colitis in the last year.

I agree to use effective birth control during the study.

Female subjects of childbearing potential must have a negative urine Qualitative HCG pregnancy test at enrolment and on the Week 1, Day 1 of the Treatment prior to administration of study drug

Exclusion Criteria

In the opinion of investigator, subject for any reason, should be excluded from the study

I haven't taken any antibiotics in the last 14 days.

I am not pregnant, breastfeeding, nor planning to become pregnant during the study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive lyophilized PRIM-DJ2727 capsules or placebo orally for 12 weeks

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

9 months

What Are the Treatments Tested in This Trial?

Interventions

• PRIM-DJ2727

Trial Overview The trial tests lyophilized PRIM-DJ2727 capsules against placebos for preventing Ulcerative Colitis relapse. It involves taking these orally and monitoring gut microbiota changes over time to see how they relate to clinical outcomes compared with a placebo.

How Is the Trial Designed?

Group I: Patients with UC will receive FMT capsules Experimental Treatment 1 Intervention

Patients with ulcerative colitis will receive fecal microbiota capsules from 3 healthy donors

Group II: Patients with UC will receive placebo Placebo Group 1 Intervention

Patients with ulcerative colitis will receive matching placebo capsules. Placebo capsule will be identical to PRIM-DJ2727 but will not contain intestinal bacteria.

Who Is Running the Clinical Trial?

The University of Texas Health Science Center, Houston

Lead Sponsor

Trials

974

Recruited

361,000+

Published Research Related to This Trial

In a pilot study of 20 patients with active ulcerative colitis, 35% achieved a clinical response and 15% reached remission after a single fecal microbiota transplantation (FMT) using a high-diversity, 2-donor fecal microbiota preparation, indicating its potential efficacy.

The study found that FMT significantly increased the diversity of the gut microbiome in patients, and the composition of the donor microbiota was linked to clinical outcomes, suggesting that donor selection may play a crucial role in treatment success.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single Delivery of High-Diversity Fecal Microbiota Preparation by Colonoscopy Is Safe and Effective in Increasing Microbial Diversity in Active Ulcerative Colitis. Jacob, V., Crawford, C., Cohen-Mekelburg, S., et al.[2022]

In a 52-week double-blind placebo-controlled study involving 32 patients with left-sided ulcerative colitis, the probiotic treatment Probio-Tec AB-25 did not show a significant advantage over placebo in maintaining clinical remission, with only 25% of the treatment group remaining in remission compared to 8% in the placebo group.

The median time to relapse was similar between the two groups, indicating that while Probio-Tec AB-25 was well tolerated, it did not provide a meaningful clinical benefit in preventing relapses of ulcerative colitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomised double-blind placebo-controlled trial with Lactobacillus acidophilus La-5 and Bifidobacterium animalis subsp. lactis BB-12 for maintenance of remission in ulcerative colitis. Wildt, S., Nordgaard, I., Hansen, U., et al.[2022]

Fecal microbiota transplantation (FMT) is significantly more effective than placebo in treating ulcerative colitis (UC), with a pooled odds ratio of 3.392 based on a systematic review of 37 studies involving 959 patients.

Administering FMT via the lower gastrointestinal tract and using a stool dosage over 275 grams were associated with higher remission rates, indicating these factors enhance the efficacy and safety of the treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of fecal microbiota transplantation for treating patients with ulcerative colitis: A systematic review and meta-analysis. Zhao, HL., Chen, SZ., Xu, HM., et al.[2021]

Fecal microbiota transplantation (FMT) was found to be as effective as glucocorticoids in inducing remission in patients with active mild to moderate ulcerative colitis, with 54.8% of FMT patients achieving remission compared to 48.3% in the glucocorticoid group.

The safety profile of FMT was superior, with significantly fewer adverse events reported (22.6% in the FMT group vs. 58.3% in the glucocorticoid group), suggesting that FMT may be a safer alternative for treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fecal microbiota transplantation versus glucocorticoids for the induction of remission in mild to moderate ulcerative colitis. Huang, C., Huang, Z., Ding, L., et al.[2022]

In a trial involving 85 patients with active ulcerative colitis, faecal microbiota transplantation (FMT) resulted in clinical remission in 27% of patients compared to only 8% in the placebo group, indicating its potential efficacy as a treatment.

The study found that FMT led to increased microbial diversity and specific bacterial changes associated with clinical outcomes, suggesting that FMT not only improves symptoms but also alters the gut microbiome in beneficial ways.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multidonor intensive faecal microbiota transplantation for active ulcerative colitis: a randomised placebo-controlled trial. Paramsothy, S., Kamm, MA., Kaakoush, NO., et al.[2022]

Probiotic therapy significantly reduces mucosal levels of proinflammatory cytokines like interleukin-1beta and interleukin-8 in patients with ulcerative colitis, suggesting a beneficial effect on the immune response.

Patients treated with probiotics also showed a lower presence of polymorphonuclear cells in their mucosal tissue compared to those receiving a placebo, indicating that probiotics may help prevent pouchitis by controlling inflammation and immune cell influx.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Probiotic therapy in the prevention of pouchitis onset: decreased interleukin-1beta, interleukin-8, and interferon-gamma gene expression. Lammers, KM., Vergopoulos, A., Babel, N., et al.[2019]

This phase Ib pilot study will be the first randomized, single-blinded, placebo-controlled trial assessing the feasibility and outcomes of fecal microbiota transplantation (FMT) in 50 pediatric patients with ulcerative colitis, with treatments administered twice a week for 6 weeks.

The study aims to evaluate the efficacy of FMT by monitoring improvements in disease symptoms using the Pediatric Ulcerative Colitis Activity Index (PUCAI) and analyzing inflammatory markers and microbiome changes, which could lead to novel therapeutic options with fewer side effects for young patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Protocol for a randomised, placebo-controlled pilot study for assessing feasibility and efficacy of faecal microbiota transplantation in a paediatric ulcerative colitis population: PediFETCh trial. Pai, N., Popov, J.[2022]

Probiotics containing bifidobacteria have shown significant efficacy in inducing remission in patients with active ulcerative colitis (UC), with a relative risk of 1.73 when using FDA-recommended assessment scales.

No significant effects were found for maintaining remission in UC patients when comparing probiotics to placebo or mesalazine, highlighting the need for validated scales to accurately assess treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Efficacy of Probiotics, Prebiotic Inulin-Type Fructans, and Synbiotics in Human Ulcerative Colitis: A Systematic Review and Meta-Analysis. Astó, E., Méndez, I., Audivert, S., et al.[2020]

Combining mesalamine with probiotics significantly improves clinical efficacy in treating ulcerative colitis compared to mesalamine alone, with better outcomes observed in both short-term (≤8 weeks) and long-term (>8 weeks) treatments.

The combination treatment does not increase the risk of adverse events, indicating that it is both effective and safe for patients with ulcerative colitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Efficacy and Safety of Mesalamine and Probiotics in Mild-to-Moderate Ulcerative Colitis: A Systematic Review and Meta-Analysis. Tian, C., Huang, Y., Wu, X., et al.[2022]

Fecal microbiota transplantation (FMT) via colonoscopy in 19 patients with mild-to-moderate ulcerative colitis showed promising results, with clinical response observed in 9 patients by week 12 and maintained in 8 patients at week 24, indicating its potential effectiveness.

The study found that specific bacteria in the gut microbiota could predict the response to FMT, with higher richness in responders compared to non-responders, suggesting a mechanism for how FMT may work in treating ulcerative colitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Serial Fecal Microbiota Infusions via Colonoscopy for Active Ulcerative Colitis: A Feasibility, Safety, and Translational Monocentric Italian Study. Lopetuso, LR., Laterza, L., Petito, V., et al.[2023]

Fecal microbiota transplantation (FMT) in 47 patients with mild to moderate ulcerative colitis (UC) led to significant clinical improvements, with 84.1% of patients showing steroid-free clinical responses and 70.5% achieving clinical remission at 4 weeks post-treatment.

The treatment was safe, with no adverse events reported in 93.2% of patients, and it resulted in increased levels of the beneficial gut bacteria Faecalibacterium prausnitzii, suggesting its potential as a biomarker for both diagnosis and therapy in UC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fecal microbiota transplantation ameliorates active ulcerative colitis. Chen, HT., Huang, HL., Xu, HM., et al.[2020]

Fecal microbiota transplantation (FMT) and mixed probiotics (VSL#3) were both found to be effective in achieving clinical remission and response in patients with active ulcerative colitis, significantly outperforming placebo treatments in a systematic review of seven randomized trials.

Both FMT and VSL#3 showed no significant increase in adverse events compared to placebo, indicating they are safe treatment options; however, VSL#3 appeared to be safer as it did not report any serious adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessing the efficacy and safety of fecal microbiota transplantation and probiotic VSL#3 for active ulcerative colitis: A systematic review and meta-analysis. Dang, X., Xu, M., Liu, D., et al.[2020]

A study involving 50 ulcerative colitis patients assessed the safety and effectiveness of a probiotic combination, showing no adverse reactions and a high adherence rate of 99.3% to the treatment.

Probiotic treatment led to significant improvements in disease activity, as indicated by a greater reduction in the Clinical Activity Index and Erythro-sedimentation rate compared to the control group, along with positive changes in stool quality and body composition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Influence of a combination of lactobacilli and bifidobacteria upon disease activity, stool pattern and nutritional status of ulcerative colitis patients]. Santana Porbén, S.[2014]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04373473

Evaluation the Safety and Efficacy of Lyophilized Fecal ... The purpose of the study is to evaluate the efficacy and safety of lyophilized PRIM-DJ2727 capsules given orally in subjects with ulcerative colitis at ...

2. centerwatch.com centerwatch.com/clinical-trials/listings/NCT04373473/evaluation-the-safety-and-efficacy-of-lyophilized-fecal-microbiota-transplantation-administered-orally-for-prevention-of-relapse-or-intestinal-inflammation-in-adults-with-ulcerative-colitis

Evaluation the Safety and Efficacy of Lyophilized Fecal ... The purpose of the study is to evaluate the efficacy and safety of lyophilized PRIM-DJ2727 capsules given orally in subjects with ulcerative ...

3. connect.careboxhealth.com connect.careboxhealth.com/en-US/trial/listing/343279

Evaluation the Safety and Efficacy of Lyophilized Fecal ... The purpose of the study is to evaluate the efficacy and safety of lyophilized PRIM-DJ2727 capsules given orally in subjects with ulcerative ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9372650/

Efficacy and safety of fecal microbiota transplantation for ... FMT is an effective treatment for patients with active UC. Significantly higher clinical and endoscopic remission rates are observed with FMT than with control ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S2468125321004003

Lyophilised oral faecal microbiota transplantation for ... Antibiotics followed by orally administered FMT was associated with the induction of remission in patients with active ulcerative colitis.