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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether a new treatment using lyophilized fecal microbiota (freeze-dried gut bacteria) is safe and effective for individuals with ulcerative colitis, a type of inflammatory bowel disease that causes gut inflammation. Participants will receive either this treatment or a placebo, alongside their usual medication, vedolizumab or ustekinumab. The trial targets those with active ulcerative colitis who are beginning biologic treatments but have not succeeded with other medications. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that fecal microbiota transplantation (FMT) holds promise for treating ulcerative colitis (UC). Studies have found that FMT can help reduce symptoms and flare-ups in UC patients. FMT is generally well-tolerated in terms of safety.

Some patients might experience mild side effects, such as stomach upset or diarrhea, but serious problems rarely occur. This treatment is currently in a Phase 2 trial, which means it has already passed initial safety tests. This phase evaluates both safety and effectiveness in a larger group of people.

Overall, evidence suggests that lyophilized fecal microbiota (LFMT) is a safe option for people with UC, with no major safety concerns reported in earlier studies. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Fecal Microbiota Transplant (FMT) is unique because it introduces beneficial bacteria from healthy donors into the gut, aiming to rebalance the gut microbiome in people with ulcerative colitis, a chronic inflammatory bowel disease. Unlike traditional treatments like steroids or immunosuppressants that primarily target inflammation or suppress the immune system, FMT works by directly altering the microbial environment, which could address underlying causes of the disease. Researchers are excited about this approach because it offers a new mechanism of action that could potentially lead to long-term remission and fewer side effects compared to current options. Additionally, the lyophilized form in capsules makes the treatment more convenient and less invasive than traditional methods of FMT delivery, such as colonoscopy or enema.

What evidence suggests that this trial's treatments could be effective for ulcerative colitis?

Research has shown that lyophilized fecal microbiota transplantation (LFMT) holds promise for people with ulcerative colitis. In this trial, some participants will receive LFMT capsules combined with either vedolizumab or ustekinumab. Studies have found that patients receiving LFMT have experienced symptom improvements. This treatment adds healthy bacteria to the gut, balancing gut bacteria and reducing inflammation. Early results suggest that LFMT can help manage ulcerative colitis symptoms, offering hope to those with this condition. While more research is needed, the initial findings are encouraging for those considering this treatment. ^{1 2 3 4 5}

Are You a Good Fit for This Trial?

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 have never used biologic drugs or they did not work for me.

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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]

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]

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]

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]

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]

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]

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]

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