Microbiota Transplant Therapy for Crohn's Disease

Overseen By Byron Vaughn

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Minnesota

Must not be taking: Antibiotics

Disqualifiers: Extensive bowel resection, Gastroparesis, Pregnancy, Active infection, others

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

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

Compensation: Varies

Number of Visits: 2

Duration: 8 weeks

120 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires that any ongoing Crohn's disease therapy, except for steroids, must be at stable doses for 4 weeks before starting the trial and remain stable during the study. Steroid use must be below 20mg by 5 days before starting, and prednisone must be tapered below 20mg after 7 days.

What data supports the effectiveness of the treatment Standardized Microbiota Transplant Therapy for Crohn's Disease?

Research shows that fecal microbiota transplantation (FMT) can help patients with Crohn's disease who do not respond to other treatments, leading to clinical remission and improvement in symptoms. FMT has also been effective in treating other conditions like recurrent Clostridioides difficile infection, suggesting its potential in managing Crohn's disease by restoring healthy gut bacteria balance. ^{1 2 3 4 5}

Is Microbiota Transplant Therapy safe for humans?

Fecal Microbiota Transplantation (FMT) has been used for various conditions, including Crohn's disease and Clostridium difficile infection, but safety data is still limited. Short-term side effects can occur, and long-term safety is not well understood, so more research is needed to fully assess its safety in humans. ^{6 7 8 9 10}

How is Microbiota Transplant Therapy different from other treatments for Crohn's Disease?

Microbiota Transplant Therapy, also known as Fecal Microbiota Transplantation (FMT), is unique because it involves transferring healthy bacteria from a donor's stool to a patient's gut to restore a balanced microbiome, which is different from traditional drug treatments that often target inflammation directly. ^{2 5 11 12 13}

What is the purpose of this trial?

Crohn's disease (CD) develops because of a disruption of homeostasis between the gut microbiota and the host immune system resulting in excessive inflammation in the intestinal tract. Current drug therapies for CD are directed at the immune system. The emergence of fecal microbiota transplantation (FMT) for the treatment of recurrent C. difficile infections (rCDI) has opened a frontier of restorative therapies targeting the gut microbiome. This study aims to assess if two forms of encapsulated FMT material (MTP101C and MTP101S) can effectively engraft in the ileum and colon of individuals with CD. This study will also assess how the impact of CD phenotype impacts engraftment. Finally this study will explore symptom and endoscopic changes before and after these two therapies.

Research Team

Byron Vaughn

Principal Investigator

University of Minnesota

Eligibility Criteria

This trial is for English-speaking adults aged 18-89 with Crohn's Disease, confirmed by clinical and histologic features. Participants must have a certain level of disease activity (SES-CD ≥ 6, or SES-CD ≥ 4 for isolated ileal disease) and be on stable CD therapies excluding high-dose steroids.

Inclusion Criteria

* Able and willing to provide informed consent.

* English speaking.

* Diagnosis of CD based on typical clinical and histologic features.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive encapsulated FMT material (MTP101C or MTP101S) to assess engraftment in the ileum and colon

8 weeks

Regular visits for monitoring and sample collection

Follow-up

Participants are monitored for safety, tolerability, and changes in clinical symptoms and endoscopic inflammation

4 months

Visits at 2 months and 6 months

Treatment Details

Interventions

• Standardized Microbiota Transplant Therapy

Trial Overview The study tests two encapsulated fecal microbiota transplant materials, MTP101C and MTP101S, to see if they can settle in the gut of Crohn's patients and improve symptoms. It also looks at how different types of Crohn's affect this process.

Participant Groups

Group I: CD patients randomized to MTP-101S Experimental Treatment 1 Intervention

Group II: CD patients randomized to MTP-101C Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

University of Minnesota

Lead Sponsor

Trials

1,459

Recruited

1,623,000+

Findings from Research

Fecal microbiota transplantation (FMT) has shown promise as an alternative treatment for Crohn's disease, particularly in patients who do not respond to conventional therapies, as demonstrated by a case where a patient achieved clinical remission and endoscopic improvement after a single FMT infusion.

Dysbiosis, or an imbalance in gut microbiota, is linked to chronic inflammation in inflammatory bowel disease (IBD), suggesting that modifying gut microbiota through FMT could help address the underlying causes of Crohn's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fecal microbiota transplantation for refractory Crohn's disease. Bak, SH., Choi, HH., Lee, J., et al.[2022]

Fecal microbiota transplantation (FMT) shows promise as a potential therapy for Crohn's disease, with some studies indicating higher rates of clinical remission compared to placebo, particularly with multiple FMT treatments.

No serious safety concerns were reported in the studies reviewed, suggesting that FMT is a safe intervention for patients with Crohn's disease, although further large-scale controlled trials are necessary to confirm its efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fecal microbiota transplantation therapy in Crohn's disease: Systematic review. Fehily, SR., Basnayake, C., Wright, EK., et al.[2022]

In a pilot study involving 15 young participants with mild to moderate Crohn's disease and ulcerative colitis, Fecal Microbiota Transplant (FMT) showed that higher residual microbial diversity after antibiotic treatment was linked to better engraftment and clinical outcomes.

The study identified that a temporary increase in Lactobacillus levels after antibiotics also correlated positively with successful engraftment, suggesting that pre-FMT microbial conditions can significantly influence treatment effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Higher alpha diversity and Lactobacillus blooms are associated with better engraftment after Fecal Microbiota Transplant in Inflammatory Bowel Disease. Zhang, YJ., Bousvaros, A., Docktor, M., et al.[2023]

Fecal microbial transplantation (FMT) from healthy donors to 19 patients with active Crohn's disease resulted in a significant increase in microbial diversity, which was associated with clinical improvement in 58% of participants.

The study found that FMT was safe, with no serious adverse events reported over 26 weeks, but the variability in clinical response suggests further research is needed to identify factors that influence the effectiveness of FMT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Increased Intestinal Microbial Diversity Following Fecal Microbiota Transplant for Active Crohn's Disease. Vaughn, BP., Vatanen, T., Allegretti, JR., et al.[2023]

In a pilot trial involving 17 adults with Crohn's disease, fecal microbiota transplantation (FMT) did not achieve the primary endpoint of successful donor microbiota implantation, but it was associated with a higher rate of steroid-free clinical remission compared to the sham group (87.5% vs 44.4% at 10 weeks).

The study found that while FMT led to a significant decrease in Crohn's Disease Endoscopic Index of Severity, indicating improved disease severity, the absence of donor microbiota engraftment was linked to disease flare-ups, suggesting that successful colonization may be crucial for maintaining remission.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fecal microbiota transplantation to maintain remission in Crohn's disease: a pilot randomized controlled study. Sokol, H., Landman, C., Seksik, P., et al.[2021]

In a study involving 139 patients with Crohn's disease who underwent fecal microbiota transplantation (FMT), 13.6% experienced mild adverse events within the first month, but no long-term adverse events were reported beyond that period.

The method of fecal microbiota preparation significantly influenced the occurrence of adverse events, with manual preparation leading to a higher rate of 21.7% compared to 8.7% for automatic methods, although this did not affect the overall efficacy of FMT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Safety of Fecal Microbiota Transplantation for Crohn's Disease: Findings from A Long-Term Study. Wang, H., Cui, B., Li, Q., et al.[2019]

Fecal microbiota transplantation (FMT) is emerging as a promising strategy to restore normal gut microbiota in patients with inflammatory bowel disease (IBD), potentially complementing existing immune modulation treatments.

While FMT shows potential efficacy, there are still uncertainties regarding the best predictors for treatment response, optimal administration methods, and the ideal characteristics of the transplanted microbiota, highlighting the need for further research on long-term outcomes and safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of fecal microbiota transplantation in inflammatory bowel disease. D'Odorico, I., Di Bella, S., Monticelli, J., et al.[2018]

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) has become a key treatment for Clostridium difficile infection, but its efficacy and safety in patients with underlying inflammatory bowel disease (IBD) are not well established, particularly regarding the risk of IBD flare-ups.

Emerging evidence suggests that FMT may also be beneficial for treating IBD itself, with promising results from randomized trials in ulcerative colitis, although the variability in study outcomes means more research is needed to clarify its clinical application.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Current Landscape and Lessons from Fecal Microbiota Transplantation for Inflammatory Bowel Disease: Past, Present, and Future. Allegretti, J., Eysenbach, LM., El-Nachef, N., et al.[2022]

Fecal microbiota transplantation (FMT) was found to be safe and effective for treating Crohn's disease, with 66.7% of the 27 patients achieving clinical remission after treatment.

Both gastroscopy and colonoscopy methods of FMT showed similar outcomes in terms of clinical remission rates and mild adverse events, while FMT significantly increased the diversity of gut microbiota in patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fecal Microbiota Transplant via Endoscopic Delivering Through Small Intestine and Colon: No Difference for Crohn's Disease. Yang, Z., Bu, C., Yuan, W., et al.[2020]

Fecal microbiota transplantation (FMT) has been successfully used as a rescue therapy for a patient with severe Crohn's disease (CD) complicated by fistula and other complications, marking a significant advancement in treatment options.

This case represents the first reported use of standardized FMT in severe CD, suggesting its potential as a novel therapeutic approach for patients who do not respond to conventional treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fecal microbiota transplantation for severe enterocolonic fistulizing Crohn's disease. Zhang, FM., Wang, HG., Wang, M., et al.[2022]

Fecal microbiota transplantation (FMT) is a low-risk alternative treatment for patients with Crohn disease, which can help restore healthy gut microbiota.

FMT effectively addresses the changes in gut microbiota that are linked to the development of Crohn disease, potentially improving patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fecal microbiota transplantation in the treatment of Crohn disease. Collins, M., DeWitt, M.[2021]

Fecal microbial transplant (FMT) showed promising results in improving symptoms of Crohn's disease in a study of 9 patients aged 12 to 19, with significant reductions in the Pediatric Crohn's Disease Activity Index (PCDAI) scores from a baseline of 19.7 to 6.4 at 2 weeks.

Most adverse events from FMT were mild and self-limiting, indicating a favorable safety profile, while 7 out of 9 patients demonstrated successful engraftment of the donor microbiome, which correlated with better clinical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fecal microbial transplant effect on clinical outcomes and fecal microbiome in active Crohn's disease. Suskind, DL., Brittnacher, MJ., Wahbeh, G., et al.[2022]

References

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

Fecal microbiota transplantation for refractory Crohn's disease. [2022]

2. Australia pubmed.ncbi.nlm.nih.gov

Fecal microbiota transplantation therapy in Crohn's disease: Systematic review. [2022]

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

Higher alpha diversity and Lactobacillus blooms are associated with better engraftment after Fecal Microbiota Transplant in Inflammatory Bowel Disease. [2023]

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

Increased Intestinal Microbial Diversity Following Fecal Microbiota Transplant for Active Crohn's Disease. [2023]

5. England pubmed.ncbi.nlm.nih.gov

Fecal microbiota transplantation to maintain remission in Crohn's disease: a pilot randomized controlled study. [2021]

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

The Safety of Fecal Microbiota Transplantation for Crohn's Disease: Findings from A Long-Term Study. [2019]

7. Australia pubmed.ncbi.nlm.nih.gov

Role of fecal microbiota transplantation in inflammatory bowel disease. [2018]

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

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

9. England pubmed.ncbi.nlm.nih.gov

The Current Landscape and Lessons from Fecal Microbiota Transplantation for Inflammatory Bowel Disease: Past, Present, and Future. [2022]

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

Fecal Microbiota Transplant via Endoscopic Delivering Through Small Intestine and Colon: No Difference for Crohn's Disease. [2020]

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

Fecal microbiota transplantation for severe enterocolonic fistulizing Crohn's disease. [2022]

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

Fecal microbiota transplantation in the treatment of Crohn disease. [2021]

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

Fecal microbial transplant effect on clinical outcomes and fecal microbiome in active Crohn's disease. [2022]