RMT for Colitis

Overseen By Amit Kulkarni, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Minnesota

Must be taking: Steroids

Disqualifiers: Pregnancy, Infectious colitis, Inflammatory bowel disease, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 30 days

30 Participants Needed

Trial Summary

What is the purpose of this trial?

Immune-related colitis from immune checkpoint inhibitors (ICI) is a common adverse effect causing significant morbidity and impairment of quality of life (QoL). Steroids are the first line of treatment for severe ICI induced Immune- mediated diarrhea and colitis (IMDC). If there is no improvement in 48 to 72 hours, other immunosuppressive agents (infliximab, vedolizumab) are recommended. However, efficacy data supporting the use of immunosuppressives for steroid refractory IMDC is limited by case reports/series. Clinical trials focusing on steroid-refractory colitis are sparse. Novel treatments for IMDC outside of blanket immunosuppression are needed. There is robust evidence to suggest that gut microbial diversity and composition is associated with both ICI efficacy and toxicity. Preliminary studies have shown that pathophysiology of immune mediated colitis may be related to loss of gut microbial diversity. Recently, multiple case series have shown the utility of fecal microbiota transplant for treatment of refractory IMDC providing the proof of concept. This is a pilot randomized placebo controlled study to assess the safety and feasibility of oral restorative microbiota therapy (RMT) in patients with steroid- refractory IMDC.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, it mentions that you should not be receiving another investigational agent or have received one within 60 days of enrollment.

What data supports the effectiveness of the treatment RMT for colitis?

Research on fecal microbiota transplantation (FMT), a similar treatment, shows it can be effective for inflammatory bowel diseases like ulcerative colitis by introducing beneficial bacteria to the gut. This suggests that RMT might also help manage colitis by improving gut health. ^{1 2 3 4 5}

Is fecal microbiota transplantation (FMT) safe for humans?

FMT is generally considered safe and well-tolerated, even in high-risk patients, with most short-term risks being mild and related to delivery methods. However, long-term side effects are not well-established, and serious adverse events have been linked to inadequate screening for multi-drug resistant organisms in some FMT products. ^{4 6 7 8 9}

How is the treatment RMT for colitis different from other treatments?

RMT, likely referring to fecal microbiota transplantation (FMT), is unique because it involves transferring stool from a healthy donor to a patient to restore a healthy balance of gut bacteria. This approach is different from traditional medications as it directly targets the gut microbiome, which can help in cases where other treatments have failed. ^{5 10 11 12 13}

Research Team

Amit Kulkarni, MD

Principal Investigator

University of Minnesota

Eligibility Criteria

This trial is for patients with severe colitis caused by immune checkpoint inhibitors, who haven't improved after high-dose steroids or other immunosuppressives. They must have adequate organ function and have received at least two doses of ICI therapy within the past six months.

Inclusion Criteria

Patients must meet one of the criteria for steroid refractory IMDC as defined

My organs are functioning well enough for me to join the study.

Patients must be able to provide written consent prior to any research-related activities

Exclusion Criteria

Known current pregnancy or breastfeeding

I have been treated for an infection in my colon.

Receiving or having received another investigational agent within 60 days of study enrollment

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive oral restorative microbiota therapy (RMT) or placebo

30 days

Initial loading dose followed by regular administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

Regular follow-up visits to assess adverse events and clinical remission

Treatment Details

Interventions

• Placebo
• RMT

Trial Overview The study tests oral restorative microbiota therapy (RMT) versus a placebo in managing steroid-refractory immune-mediated diarrhea and colitis (IMDC). It's a pilot randomized controlled trial to evaluate RMT's safety and feasibility.

Participant Groups

Group I: RMT group Experimental Treatment 1 Intervention

16 patients will be randomized to Oral restorative microbiota therapy (RMT). Consenting eligible participants receive a loading dose of RMT capsules.

Group II: active placebo Placebo Group 1 Intervention

participants in the placebo arm will receive an identical looking placebo capsules

Who Is Running the Clinical Trial?

University of Minnesota

Lead Sponsor

Trials

1,459

Recruited

1,623,000+

Findings from Research

In a review of 12 published studies on fecal microbiota transplantation (FMT) for inflammatory bowel disease (IBD), only one study suggested a significant donor effect, while the majority showed no statistically significant differences in efficacy based on donor material.

Despite the lack of strong evidence for donor effects, the study highlights that the existing data cannot completely rule out their potential clinical importance, indicating a need for larger, well-designed trials to explore this further.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Re-Evaluating the Evidence for Faecal Microbiota Transplantation 'Super-Donors' in Inflammatory Bowel Disease. Olesen, SW., Gerardin, Y.[2021]

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 study of 30 patients with ulcerative colitis who did not respond to standard treatments, 70% showed a clinical response to fecal microbial transplantation (FMT) after 12 weeks, with 43.3% achieving both clinical and endoscopic remission.

FMT was found to be a safe alternative to immunosuppressive therapies, with only mild adverse events reported in 23.3% of patients, suggesting it could be a promising option for those with refractory ulcerative colitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fecal microbiota transplantation is a rescue treatment modality for refractory ulcerative colitis. Uygun, A., Ozturk, K., Demirci, H., et al.[2018]

In a double-blind randomized trial involving 50 patients with mild to moderately active ulcerative colitis, fecal microbiota transplantation (FMT) from healthy donors did not show a statistically significant improvement in clinical remission compared to autologous fecal microbiota, with 30.4% of the FMT group achieving remission versus 20.0% in the control group.

Despite the lack of significant differences in remission rates, the microbiota of patients who responded to FMT showed similarities to their healthy donors, suggesting that specific microbial profiles may be associated with treatment response and warrant further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Findings From a Randomized Controlled Trial of Fecal Transplantation for Patients With Ulcerative Colitis. Rossen, NG., Fuentes, S., van der Spek, MJ., et al.[2022]

Fecal microbiota transplantation (FMT) is recommended for treating recurrent Clostridium difficile infections and has shown benefits for various gastrointestinal disorders, but safety data is still limited due to the rapid adoption of the technique without extensive long-term studies.

Capsulized FMT therapy offers a promising solution for long-term maintenance and reduces the need for invasive procedures, indicating a shift towards safer and more tolerable methods of delivering FMT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Current research progress and thinking of fecal microbiota transplantation for the treatment of gastrointestinal disorders]. Li, N., Tian, H.[2020]

Fecal microbiota transplantation (FMT) is a generally safe and well-tolerated procedure for treating recurrent Clostridioides difficile infections, even in high-risk patients, with most short-term risks being mild and related to delivery methods.

Recent concerns have emerged regarding serious adverse events linked to FMT products from stool banks that do not screen for multi-drug resistant organisms, highlighting the need for improved safety protocols.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fecal Microbiota Transplantation: Is It Safe? Park, SY., Seo, GS.[2021]

Fecal microbiota transplantation (FMT) showed effectiveness in treating active ulcerative colitis (UC) in a small study of 7 patients, with all participants experiencing improvements in their Mayo scores after the procedure.

While some patients experienced mild and transient side effects like fever and diarrhea, no severe adverse reactions were reported, suggesting that FMT is a relatively safe option for managing active UC, although further research is needed to assess long-term outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[A pilot study of treating ulcerative colitis with fecal microbiota transplantation]. Ren, R., Sun, G., Yang, Y., et al.[2022]

References

1. Spain pubmed.ncbi.nlm.nih.gov

[Evolution and treatment response in microscopic colitis]. [2006]

2. Korea (South) pubmed.ncbi.nlm.nih.gov

The practice of fecal microbiota transplantation in inflammatory bowel disease. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Re-Evaluating the Evidence for Faecal Microbiota Transplantation 'Super-Donors' in Inflammatory Bowel Disease. [2021]

4. 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]

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

Fecal microbiota transplantation is a rescue treatment modality for refractory ulcerative colitis. [2018]

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

Findings From a Randomized Controlled Trial of Fecal Transplantation for Patients With Ulcerative Colitis. [2022]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Fecal Microbiota Transplantation in Treatment of Inflammatory Bowel Disease in the Pediatric Population: A Systematic Review and Meta-Analysis. [2023]

8. China pubmed.ncbi.nlm.nih.gov

[Current research progress and thinking of fecal microbiota transplantation for the treatment of gastrointestinal disorders]. [2020]

9. Korea (South) pubmed.ncbi.nlm.nih.gov

Fecal Microbiota Transplantation: Is It Safe? [2021]

10. Belgium pubmed.ncbi.nlm.nih.gov

Fecal microbiota transplantation in ulcerative colitis. [2020]

11. China pubmed.ncbi.nlm.nih.gov

[A pilot study of treating ulcerative colitis with fecal microbiota transplantation]. [2022]

12. Switzerland pubmed.ncbi.nlm.nih.gov

Ulcerative Colitis in Response to Fecal Microbiota Transplantation via Modulation of Gut Microbiota and Th17/Treg Cell Balance. [2023]

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

Role of multidetector computed tomography in patients with acute infectious colitis. [2022]