Probiotic R-3750 for Ulcerative Colitis

Recruiting in Palo Alto (17 mi)

+4 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

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

Trial Summary

What is the purpose of this trial?

The goal of this study is to determine the safety and tolerability of orally taken probiotic (R-3750) in patients with mild to moderate ulcerative colitis. Patients will take 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.

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.

What data supports the effectiveness of the treatment R-3750 for ulcerative colitis?

Research shows that probiotics, especially those containing bifidobacteria, can help treat active ulcerative colitis by reducing inflammation and improving symptoms. This suggests that similar probiotic treatments like R-3750 might also be effective. ^{1 2 3 4 5}

Is Probiotic R-3750 safe for humans?

Probiotic treatments, including combinations of lactobacilli and bifidobacteria, have been studied in ulcerative colitis patients and found to be generally safe, with no adverse reactions reported in one study. Another study on Lactobacillus rhamnosus GG, a similar probiotic, also reported no severe adverse events, indicating that probiotics are generally safe for human use. ^{3 6 7 8 9}

How is the treatment R-3750 different from other treatments for ulcerative colitis?

R-3750 is a probiotic treatment, which means it uses live microorganisms to help improve gut health, potentially offering a natural alternative to traditional medications. Unlike standard drugs, probiotics like R-3750 may help maintain remission and improve symptoms by positively influencing the gut flora, which is thought to play a role in ulcerative colitis. ^{1 3 4 10 11}

Research Team

Eligibility Criteria

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 am between 18 and 65 years old.

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.

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

Trial Timeline

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

Treatment Details

Interventions

• R-3750 (Probiotic)

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+

Dr. Gianrico Farrugia

Mayo Clinic

Chief Executive Officer since 2019

MD from University of Malta Medical School

Dr. Richard Afable

Mayo Clinic

Chief Medical Officer

MD from Loyola Stritch School of Medicine

University of Colorado, Denver

Collaborator

Trials

1,842

Recruited

3,028,000+

Aviva Abosch

University of Colorado, Denver

Chief Medical Officer since 2019

MD

Uday B. Kompella

University of Colorado, Denver

Chief Executive Officer since 2015

PhD in Pharmaceutical Sciences

Findings from Research

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]

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]

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 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]

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]

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]

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 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]

References

1. 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]

2. United States pubmed.ncbi.nlm.nih.gov

Effect of probiotics on pro-inflammatory cytokines and NF-kappaB activation in ulcerative colitis. [2022]

3. 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]

4. United States pubmed.ncbi.nlm.nih.gov

The probiotic preparation, VSL#3 induces remission in patients with mild-to-moderately active ulcerative colitis. [2022]

5. 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]

6. United Arab Emirates 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. [2019]

7. 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]

8. Switzerland 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. [2023]

9. England 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. [2022]

10. United States pubmed.ncbi.nlm.nih.gov

Synbiotic therapy: a promising new adjunctive therapy for ulcerative colitis. [2019]

11. England pubmed.ncbi.nlm.nih.gov

Maintaining remission of ulcerative colitis with the probiotic Escherichia coli Nissle 1917 is as effective as with standard mesalazine. [2022]