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

Trial Summary

What is the purpose of this trial?

This trial is testing freeze-dried PRIM-DJ2727 capsules taken by mouth in people with ulcerative colitis who are not currently experiencing symptoms. The treatment might work by changing gut bacteria to help keep the disease from coming back.

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.

What data supports the effectiveness of the treatment PRIM-DJ2727, Lyophilized Fecal Microbiota Transplantation, for ulcerative colitis?

Research shows that fecal microbiota transplantation (FMT) can increase microbial diversity and help induce remission in ulcerative colitis. Additionally, probiotics have been found to help maintain remission in patients with this condition. ^{1 2 3 4 5}

Is the treatment safe for humans?

Research on probiotics and fecal microbiota transplantation (FMT) for ulcerative colitis shows that these treatments are generally safe, with most studies reporting no significant adverse events. In one study, 93.2% of patients experienced no adverse events after FMT, and another study found no adverse reactions after probiotic treatment. ^{5 6 7 8 9}

How is the treatment PRIM-DJ2727 different from other treatments for ulcerative colitis?

PRIM-DJ2727 is unique because it involves lyophilized fecal microbiota transplantation, which is a novel way to change the gut bacteria to help treat ulcerative colitis, unlike traditional treatments that may use drugs or probiotics alone. ^{5 10 11 12 13}

Eligibility Criteria

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.

I am 18 years old or older.

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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) 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]

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]

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]

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]

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]

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]

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]

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]

References

1. England 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. [2022]

2. England 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. [2022]

3. Australia pubmed.ncbi.nlm.nih.gov

Efficacy and safety of fecal microbiota transplantation for treating patients with ulcerative colitis: A systematic review and meta-analysis. [2021]

4. England pubmed.ncbi.nlm.nih.gov

Fecal microbiota transplantation versus glucocorticoids for the induction of remission in mild to moderate ulcerative colitis. [2022]

5. United States 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. [2022]

6. Greece pubmed.ncbi.nlm.nih.gov

Fecal microbiota transplantation ameliorates active ulcerative colitis. [2020]

7. Spain 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]. [2014]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Serial Fecal Microbiota Infusions via Colonoscopy for Active Ulcerative Colitis: A Feasibility, Safety, and Translational Monocentric Italian Study. [2023]

9. England 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. [2022]

10. England pubmed.ncbi.nlm.nih.gov

Multidonor intensive faecal microbiota transplantation for active ulcerative colitis: a randomised placebo-controlled trial. [2022]

11. Switzerland 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. [2020]

12. United States 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. [2020]

13. England pubmed.ncbi.nlm.nih.gov

Probiotic therapy in the prevention of pouchitis onset: decreased interleukin-1beta, interleukin-8, and interferon-gamma gene expression. [2019]