Probiotic R-3750 for Ulcerative Colitis

Recruiting at 4 trial locations

Overseen By Christian Freguia, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Rise Therapeutics LLC

Must be taking: Aminosalicylates

Must not be taking: Immunosuppressants, Anti-cancer drugs, Steroids, Probiotics

Disqualifiers: Severe UC, Active infection, Autoimmune, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 6 weeks

36 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if a new probiotic treatment, R-3750, is safe and tolerable for individuals with mild to moderate ulcerative colitis, a condition that causes inflammation in the colon. Participants will take the probiotic orally and report their symptoms, while doctors assess inflammation levels through blood and stool tests. Suitable candidates will have a confirmed diagnosis of mild to moderate ulcerative colitis and remain stable on their current medication without plans for imminent changes. As a Phase 1 trial, participants will be among the first to receive this new treatment, aiding researchers in understanding its effects in people.

Will I have to stop taking my current medications?

If you are currently taking aminosalicylates and have been on a stable dose for at least 4 weeks, you can continue taking them during the trial. However, you cannot start any new medications other than the study drug, and you must stop using probiotics one week before and during the trial.

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

Research has shown that R-3750, a new probiotic treatment, is safe for people with mild to moderate ulcerative colitis. Studies have found that patients tolerate it well, with no major safety issues reported. Specifically, results demonstrated both safety and positive effects in patients. Probiotics like R-3750, which contain helpful bacteria, are generally considered safe for ulcerative colitis. This treatment appears to support the body's immune system beneficially, without causing serious side effects. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for ulcerative colitis, which often involve anti-inflammatory drugs or immunosuppressants, R-3750 is a probiotic. Researchers are excited about R-3750 because it introduces live beneficial bacteria that could help restore a healthy balance in the gut microbiome. This approach is different because it aims to naturally support gut health rather than just suppress symptoms. If successful, R-3750 could offer a gentler, potentially side-effect-free alternative for managing ulcerative colitis.

What evidence suggests that this treatment might be an effective treatment for ulcerative colitis?

Research shows that R-3750, a new synthetic probiotic, could help treat mild to moderate ulcerative colitis. Studies have found that it improves the body's handling of inflammation, crucial for managing this condition. R-3750 might also help maintain symptom remission and prevent recurrence. It balances gut bacteria and boosts immune function. Early evidence suggests that R-3750 is safe for patients. ^{1 2 4 6 7}

Are You a Good Fit for This Trial?

Adults aged 18-65 with mild to moderate ulcerative colitis can join this trial. They must use birth control, avoid vaccinations during the study, and be able to consent. Those with recent drug abuse, probiotic use, chronic infections including COVID-19, major autoimmune diseases besides UC, high-dose steroid treatment for UC, severe allergies to probiotics or a history of stroke are excluded.

Inclusion Criteria

I agree to use effective birth control during and 30 days after the study.

I will not get any vaccines during the study, including flu or COVID shots.

Ability to provide written informed consent

Exclusion Criteria

I haven't had chest infections, sinusitis, or COVID-19 in the last 3 months.

Major active systemic autoimmune disease other than UC

History of alcohol or drug abuse within the past 2 years

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive an oral dosage of probiotic (R-3750) and provide patient-reported and physician-scored measures of their colitis. Blood and fecal evaluations of inflammation and assessment of probiotic (R-3750) on fecal levels will also be measured.

6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• R-3750

Trial Overview The trial is testing the safety and effects of R-3750—a probiotic taken orally—on patients with ulcerative colitis. Participants will report their symptoms and undergo blood and stool tests to measure inflammation and how R-3750 affects fecal levels.

Who Is Running the Clinical Trial?

Rise Therapeutics LLC

Lead Sponsor

Trials

5

Recruited

180+

Mayo Clinic

Collaborator

Trials

3,427

Recruited

3,221,000+

University of Colorado, Denver

Collaborator

Trials

1,842

Recruited

3,028,000+

Published Research Related to This Trial

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]

In a study of 30 patients with mild-to-moderate ulcerative colitis, those receiving probiotic supplementation showed significant improvements in disease activity, as indicated by a reduction in the Partial Mayo score and stool frequency compared to the placebo group.

Probiotic therapy also led to beneficial changes in biochemical markers, including increased hemoglobin and hematocrit levels, and decreased C-reactive protein, suggesting an overall positive impact on inflammation and blood health in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Probiotic supplementation induces remission and changes in the immunoglobulins and inflammatory response in active ulcerative colitis patients: A pilot, randomized, double-blind, placebo-controlled study. Agraib, LM., Yamani, MI., Tayyem, R., et al.[2022]

A pediatric patient with ulcerative colitis experienced a longer remission period, symptom resolution, and improved quality of life after receiving synbiotic therapy, which combines prebiotics and probiotics.

The review of existing literature indicates that prebiotic, probiotic, and synbiotic therapies may enhance clinical outcomes in adults with ulcerative colitis, suggesting potential benefits across different age groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Synbiotic therapy: a promising new adjunctive therapy for ulcerative colitis. Haskey, N., Dahl, WJ.[2019]

In a study of 30 patients with mild to moderate ulcerative colitis, adding probiotics to standard sulfasalazine treatment significantly reduced inflammation markers, such as interleukin-6 and TNF-alpha, after 8 weeks.

Probiotics not only improved inflammatory responses but also showed potential in maintaining remission and preventing relapse in ulcerative colitis patients, suggesting they could be a beneficial adjunct therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of probiotics on pro-inflammatory cytokines and NF-kappaB activation in ulcerative colitis. Hegazy, SK., El-Bedewy, MM.[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]

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]

Lactobacillus rhamnosus GG (LGG) was found to be safe and effective in inducing remission in patients with mild to moderate ulcerative colitis, with 37% of participants achieving disease remission after one month of treatment.

In a study involving 76 patients, LGG showed no significant difference in efficacy or safety between two different doses, and no serious adverse events were reported, indicating its potential as a monotherapy option for ulcerative colitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Potential Role of Lactobacillus rhamnosus GG Administration as Monotherapy in Ulcerative Colitis Patients with Mild-Moderate Clinical Activity. Pagnini, C., Di Paolo, MC., Urgesi, R., et al.[2023]

A review of 46 clinical trials on the use of probiotics and prebiotics for treating Inflammatory Bowel Diseases (IBD) found that while many trials showed positive outcomes, particularly in ulcerative colitis, there was no clear superiority among different probiotic strains.

Specifically, 12 out of 16 randomized controlled trials for ulcerative colitis were successful, suggesting that multi-agent mixtures like VSL#3 may be more effective, while Lactobacillus rhamnosus GG showed limited benefit, especially in Crohn's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Manipulation of intestinal microbial flora for therapeutic benefit in inflammatory bowel diseases: review of clinical trials of probiotics, pre-biotics and synbiotics. Heilpern, D., Szilagyi, A.[2019]

In a multicenter trial involving 147 adult patients with mild-to-moderate ulcerative colitis, the high-potency probiotic VSL#3 significantly improved disease activity scores at 6 weeks compared to placebo, with 32.5% of patients showing over 50% improvement.

By 12 weeks, VSL#3 led to remission in 42.9% of patients, compared to only 15.7% in the placebo group, demonstrating its efficacy in inducing remission and reducing symptoms in ulcerative colitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The probiotic preparation, VSL#3 induces remission in patients with mild-to-moderately active ulcerative colitis. Sood, A., Midha, V., Makharia, GK., 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]

In a study involving 327 patients with ulcerative colitis over 12 months, the probiotic Escherichia coli Nissle 1917 was found to be as effective as the standard treatment mesalazine in preventing relapses, with similar rates of relapse in both groups (36.4% for E. coli Nissle 1917 and 33.9% for mesalazine).

Both treatments demonstrated a very good safety profile and tolerability, indicating that E. coli Nissle 1917 is a viable alternative to mesalazine for maintaining remission in ulcerative colitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Maintaining remission of ulcerative colitis with the probiotic Escherichia coli Nissle 1917 is as effective as with standard mesalazine. Kruis, W., Fric, P., Pokrotnieks, J., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05666960

R-3750 in Patients With Mild to Moderate Ulcerative Colitis There are three types of violations: Failure to submit required clinical trial information; Submission of false or misleading clinical trial information ...

2. journals.lww.com journals.lww.com/ajg/fulltext/2025/10002/s1633_clinical_evaluation_of_r_3750__a_novel.1633.aspx

S1633 Clinical Evaluation of R-3750: A Novel Synthetic... R-3750 demonstrates a favorable safety and efficacy profile with supportive mechanistic data. By engaging the mucosal immune axis and remodeling the microbiome, ...

3. withpower.com withpower.com/trial/phase-1-colitis-2023-e9789

Probiotic R-3750 for Ulcerative Colitis Probiotics not only improved inflammatory responses but also showed potential in maintaining remission and preventing relapse in ulcerative colitis patients, ...

4. risetherapeutics.com risetherapeutics.com/news/71-rise-therapeutics-reports-ulcerative-colitis-dose-escalation-clinical-results-for-r-3750-at-the-digestive-disease-week-ddw-conference-in-san-diego-may-3-6

Rise Therapeutics Reports Ulcerative Colitis Dose ... R-3750, a novel oral immunotherapy, is a synthetic biology-based medicine in development for the treatment of Inflammatory Bowel Disease (IBD).

5. reporter.nih.gov reporter.nih.gov/search/bAeZ8SYzo0Oo2Q4X4xlw6w/project-details/11193481

Project Details New data from our Phase 1 clinical trial in patients suffering from ulcerative colitis (NCT05666960) showed that R-3750 was safe and yielded promising ...

6. mayo.edu mayo.edu/research/clinical-trials/cls-20545888

R-3750 in Patients With Mild to Moderate Ulcerative Colitis The purpose of this study is to determine safety and tolerability of orally delivered R-3750 in mild to moderate patients with ulcerative colitis.

7. prnewswire.com prnewswire.com/news-releases/rise-therapeutics-reports-ulcerative-colitis-dose-escalation-clinical-results-for-r-3750-at-the-digestive-disease-week-ddw-conference-in-san-diego-may-3-6-302421697.html

Rise Therapeutics Reports Ulcerative Colitis Dose ... Results highlight safety and promising clinical responses of R-3750, along with biomarker results demonstrating a differentiated immune mechanism.