Fecal Microbiota Transplant for Ulcerative Colitis

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Alberta

Must be taking: Vedolizumab, Ustekinumab

Must not be taking: Cyclosporine, Tacrolimus, Thalidomide, others

Disqualifiers: Severe UC, Indeterminate colitis, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 8 weeks

40 Participants Needed

Trial Summary

What is the purpose of this trial?

To compare the safety and efficacy of concomitant LFMT versus placebo in UC patients who are starting vedolizumab or ustekinumab.

Will I have to stop taking my current medications?

The trial requires stopping certain medications before joining. You must stop using rectal/topical therapies 2 weeks before, cyclosporine, tacrolimus, or thalidomide 4 weeks before, and adalimumab or infliximab 8 weeks before. Vedolizumab must be stopped 8 weeks before, and ustekinumab 12 weeks before. Prednisone over 30 mg/day is not allowed.

What data supports the effectiveness of the treatment Lyophilized Fecal Microbiota (LFMT) for ulcerative colitis?

Research shows that fecal microbiota transplantation (FMT), including the lyophilized (freeze-dried) form, can help some patients with ulcerative colitis achieve remission, meaning their symptoms improve significantly. One study found that oral lyophilized FMT was effective, with one donor achieving 100% success in inducing remission in patients. ^{1 2 3 4 5}

Is fecal microbiota transplantation (FMT) safe for humans?

Research on fecal microbiota transplantation (FMT) for ulcerative colitis suggests it is generally safe, with studies focusing on its safety and feasibility, including long-term use. While these studies primarily target ulcerative colitis, they provide valuable safety insights for FMT in humans. ^{1 4 5 6 7}

How is fecal microbiota transplantation different from other treatments for ulcerative colitis?

Fecal microbiota transplantation (FMT) is unique because it involves transferring stool from a healthy donor to a patient to restore a balanced gut microbiome, which is different from traditional drug treatments that target inflammation directly. This approach is novel as it aims to correct gut dysbiosis (imbalance of gut bacteria) rather than just suppressing symptoms. ^{7 8 9 10 11}

Eligibility Criteria

This trial is for adults aged 18-75 with ulcerative colitis, confirmed by a doctor using standard tests. Participants must have active symptoms and be starting vedolizumab or ustekinumab treatment but can't have used certain medications recently. Women who can bear children must use contraception during the trial.

Inclusion Criteria

My doctor has chosen vedolizumab or ustekinumab for my treatment.

My ulcerative colitis was confirmed by a doctor using specific tests.

I am between 18 and 75 years old.

Exclusion Criteria

Severe underlying disease such that the patient is not expected to survive for at least 30 days

I haven't had treatment for C. difficile or other gut infections in the last 4 weeks.

Neutropenia with absolute neutrophil count <0.5 x 109/L

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive LFMT or placebo capsules along with vedolizumab or ustekinumab for 8 weeks

8 weeks

Initial visit (in-person) for loading dose, followed by daily administration at home

Follow-up

Participants are monitored for safety and effectiveness after treatment

16 weeks

Treatment Details

Interventions

• Lyophilized Fecal Microbiota (LFMT)
• Placebo

Trial Overview The study is testing LFMT against a placebo in patients beginning biologic treatments for ulcerative colitis to see which is safer and more effective. Patients will either receive this new fecal microbiota therapy or a dummy treatment as they start their prescribed medication.

Participant Groups

Group I: LFMT capsules + vedolizumab Experimental Treatment 1 Intervention

The initial loading dose is 15 capsules, administered on day 0, in the clinic under direct observation, followed by 5 capsules daily starting on day 1 for 8 weeks at home. All subsequent doses will be dispensed to participants.

Group II: LFMT capsules + ustekinumab Experimental Treatment 1 Intervention

The initial loading dose is 15 capsules, administered on day 0, in the clinic under direct observation, followed by 5 capsules daily starting on day 1 for 8 weeks at home. All subsequent doses will be dispensed to participants.

Group III: Placebo capsules + vedolizumab Placebo Group 1 Intervention

The placebo capsules will appear identical to the LFMT capsules; however, the capsules will contain 2 ingredients: trehalose and neusilin, which are components in LFMT capsules.

Group IV: Placebo capsules + ustekinumab Placebo Group 1 Intervention

The placebo capsules will appear identical to the LFMT capsules; however, the capsules will contain 2 ingredients: trehalose and neusilin, which are components in LFMT capsules.

Who Is Running the Clinical Trial?

University of Alberta

Lead Sponsor

Trials

957

Recruited

437,000+

Findings from Research

In a trial involving 35 patients with active ulcerative colitis, oral lyophilised faecal microbiota transplantation (FMT) led to a significant remission rate, with 53% of patients achieving corticosteroid-free clinical remission compared to 15% in the placebo group.

Continuing FMT after initial treatment resulted in 100% of patients maintaining remission at week 56, suggesting that oral FMT could be a promising long-term treatment option for ulcerative colitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lyophilised oral faecal microbiota transplantation for ulcerative colitis (LOTUS): a randomised, double-blind, placebo-controlled trial. Haifer, C., Paramsothy, S., Kaakoush, NO., et al.[2022]

Faecal microbiota transplantation (FMT) showed variable efficacy in treating ulcerative colitis (UC), with one donor achieving 100% efficacy while another only 36%, highlighting the importance of donor selection.

The effective donor's gut microbiome exhibited long-term stability and higher species evenness, which were associated with better clinical outcomes, suggesting that these characteristics could be key metrics for selecting FMT donors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Microbial determinants of effective donors in faecal microbiota transplantation for UC. Haifer, C., Luu, LDW., Paramsothy, S., et al.[2023]

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]

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]

In a clinical trial involving 73 adults with mild to moderate ulcerative colitis, anaerobically prepared donor fecal microbiota transplantation (FMT) led to a higher remission rate (32%) compared to autologous FMT (9%) after 8 weeks, indicating its efficacy in inducing remission.

Among those who achieved remission with donor FMT, 42% maintained it for 12 months, suggesting potential for long-term benefits, although further research is needed to confirm safety and longer-term outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of Fecal Microbiota Transplantation on 8-Week Remission in Patients With Ulcerative Colitis: A Randomized Clinical Trial. Costello, SP., Hughes, PA., Waters, O., et al.[2020]

The study demonstrated that daily oral administration of frozen encapsulated fecal microbiota transplantation (cFMT) is safe and well-tolerated in patients with mild to moderate ulcerative colitis (UC), with no treatment-related adverse events reported.

Two out of six subjects receiving cFMT achieved clinical remission, suggesting that cFMT may help maintain beneficial changes in gut microbiota and improve clinical outcomes, although further research is needed to confirm these findings and address home storage issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daily, oral FMT for long-term maintenance therapy in ulcerative colitis: results of a single-center, prospective, randomized pilot study. Crothers, JW., Chu, ND., Nguyen, LTT., et al.[2022]

Faecal microbiota transplantation (FMT) has shown effectiveness in inducing remission in active ulcerative colitis (UC), with a clinical remission rate of 28% in FMT patients compared to 9% in placebo groups based on a meta-analysis of randomized controlled trials involving 277 patients.

The study found no major short-term safety concerns associated with FMT, suggesting it is a safe option for patients with UC, although further research is needed to optimize treatment protocols.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systematic review with meta-analysis: faecal microbiota transplantation for the induction of remission for active ulcerative colitis. Costello, SP., Soo, W., Bryant, RV., et al.[2022]

In a study involving 7 patients with mild to moderate ulcerative colitis, fecal microbiota transplantation (FMT) achieved a donor similarity index (DSI) of 40-50% in about two-thirds of recipients, indicating some level of microbiota engraftment.

Despite achieving this level of engraftment, only one patient experienced a temporary clinical improvement, suggesting that while FMT can alter the microbiota, its efficacy in achieving lasting remission in ulcerative colitis may require further investigation and optimization.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low Level Engraftment and Improvement following a Single Colonoscopic Administration of Fecal Microbiota to Patients with Ulcerative Colitis. Damman, CJ., Brittnacher, MJ., Westerhoff, M., et al.[2022]

In a survey of 262 ulcerative colitis patients, 56.1% expressed willingness to undergo fecal microbiota transplantation (FMT) as a treatment option, motivated primarily by the effectiveness of the procedure and the failure of other therapies.

Concerns about FMT included the potential transmission of infectious agents and contamination of the stool graft, highlighting the need for safe implementation practices in this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Patient perception and approval of fecal microbiota transplantation (FMT) as an alternative treatment option for ulcerative colitis]. Roggenbrod, S., Schuler, C., Haller, B., et al.[2022]

Fecal microbiota transplantation (FMT) successfully induced and maintained clinical remission in a patient with ulcerative colitis (UC) who was allergic to 5-aminosalicylic acid (5-ASA), demonstrating its potential as an alternative treatment.

This case highlights the efficacy of FMT in reconstructing intestinal microbiota for patients with refractory UC, especially when conventional treatments like steroid therapy fail.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fecal microbiota transplantation treatment for refractory ulcerative colitis with allergy to 5-aminosalicylic acid: A case report. Wang, HG., Liu, SP., Ma, TH., et al.[2021]

Fecal microbiota transplantation (FMT) was attempted in a three-year-old girl with severe ulcerative colitis (UC) after conventional treatments failed, but it did not lead to remission and the patient ultimately required colectomy.

The patient experienced abdominal pain and fever after each of the six FMT sessions, and analyses showed that the donor microbiota was not retained, suggesting that the severity of her UC and the timing of FMT may have influenced the poor outcome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Failure of Fecal Microbiota Transplantation in a Three-Year-Old Child with Severe Refractory Ulcerative Colitis. Kumagai, H., Yokoyama, K., Imagawa, T., et al.[2022]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Lyophilised oral faecal microbiota transplantation for ulcerative colitis (LOTUS): a randomised, double-blind, placebo-controlled trial. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Microbial determinants of effective donors in faecal microbiota transplantation for UC. [2023]

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

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

4. China pubmed.ncbi.nlm.nih.gov

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

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

Effect of Fecal Microbiota Transplantation on 8-Week Remission in Patients With Ulcerative Colitis: A Randomized Clinical Trial. [2020]

6. England pubmed.ncbi.nlm.nih.gov

Daily, oral FMT for long-term maintenance therapy in ulcerative colitis: results of a single-center, prospective, randomized pilot study. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Systematic review with meta-analysis: faecal microbiota transplantation for the induction of remission for active ulcerative colitis. [2022]

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

Low Level Engraftment and Improvement following a Single Colonoscopic Administration of Fecal Microbiota to Patients with Ulcerative Colitis. [2022]

9. Germany pubmed.ncbi.nlm.nih.gov

[Patient perception and approval of fecal microbiota transplantation (FMT) as an alternative treatment option for ulcerative colitis]. [2022]

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

Fecal microbiota transplantation treatment for refractory ulcerative colitis with allergy to 5-aminosalicylic acid: A case report. [2021]

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

Failure of Fecal Microbiota Transplantation in a Three-Year-Old Child with Severe Refractory Ulcerative Colitis. [2022]