Fecal Microbiota Transplant for Ulcerative Colitis

(FUEL Trial)

Overseen By Aida Fernandes, MBA

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Hamilton Health Sciences Corporation

Must be taking: 5-ASA, Azathioprine, Anti-TNF

Must not be taking: Antibiotics

Disqualifiers: Severe illness, Pregnancy, Hepatic, others

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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 6

Duration: 9 weeks

200 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness of fecal microbiota transplants (FMT) for individuals with active ulcerative colitis (UC), a condition that causes inflammation and sores in the digestive tract. The goal is to determine if stool from new, healthy donors can induce remission, meaning the symptoms disappear. Researchers aim to discover if ongoing FMT treatments can maintain symptom relief for an extended period. Suitable candidates for this trial are those experiencing active UC symptoms that affect daily life and have not changed their medication in the last 12 weeks. As an unphased trial, this study offers a unique opportunity to explore a novel treatment approach for UC.

Will I have to stop taking my current medications?

You can continue taking certain medications like 5-ASA, azathioprine, 6-mercaptopurine, or anti-TNF therapy if you've been on a stable dose for at least 12 weeks before joining the trial. If you're on steroids, you can stay on a stable or tapering dose as long as it's not increased. Probiotic therapy is also allowed.

What prior data suggests that Fecal Microbiota Transplant is safe for ulcerative colitis patients?

Research has shown that Fecal Microbiota Transplant (FMT) is generally safe and is already used to treat a difficult gut infection called C. difficile. Studies have found that FMT can alter the gut in ways that might benefit people with ulcerative colitis. In one study, 70 out of 261 patients who received FMT experienced symptom improvement and went into remission.

While researchers continue to study FMT for ulcerative colitis, it has been well-tolerated in other treatments. Some mild side effects, such as stomach upset or diarrhea, might occur, but serious problems are rare. The treatment uses stool from healthy donors, which undergoes careful screening to ensure it is disease-free, enhancing safety for participants. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike traditional treatments for ulcerative colitis, which often involve anti-inflammatory drugs or immune system suppressants, fecal microbiota transplant (FMT) is unique because it uses healthy donor stool to restore balance to the gut microbiome. Most treatments focus on reducing symptoms by controlling inflammation, but FMT targets the underlying gut bacteria imbalance that might be contributing to the condition. Researchers are excited about FMT because it has the potential to address the root cause of ulcerative colitis rather than just managing its symptoms, offering a new approach that could improve long-term outcomes for patients.

What evidence suggests that Fecal Microbiota Transplant might be an effective treatment for Ulcerative Colitis?

Research has shown that fecal microbiota transplantation (FMT) can help some people with ulcerative colitis (UC) feel better. Studies have found that FMT reduces inflammation in the colon, a common issue for those with UC. Some patients experience significant improvement in their symptoms, known as clinical remission, after receiving FMT. However, the effectiveness of FMT can depend on the donor, with some donors proving more effective than others. While FMT is already used for certain infections, its use in treating UC remains under investigation. Participants in this trial will receive open-label FMT therapy from a related or unrelated healthy donor screened for known communicable diseases. ^{1 2 4 5 6}

Who Is on the Research Team?

Paul Moayyedi, MD

Principal Investigator

HHSC/McMaster

Are You a Good Fit for This Trial?

This trial is for adults over 18 with active Ulcerative Colitis, as shown by a Mayo score greater than 3. Participants must not be in another UC study, hospitalized for severe UC, or have had recent changes in their UC medication. Women who can have children must agree to use contraception.

Inclusion Criteria

I am willing to use birth control as required.

A Mayo endoscopic score >0

My ulcerative colitis is active with a Mayo score over 3.

Exclusion Criteria

I have been hospitalized for severe ulcerative colitis.

I have not taken antibiotics in the last 30 days.

My ulcerative colitis medication has been increased in the last 3 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

All UC patients receive FMT from a screened donor for 8 weeks to induce remission

9 weeks

Weekly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 years

Regular visits (in-person) every 6 months

Long-term follow-up

Maintenance of remission of UC after three years in those who achieve initial remission with FMT

3 years

What Are the Treatments Tested in This Trial?

Interventions

• Fecal Microbiota Transplant

Trial Overview The trial is testing the effectiveness of fecal microbiota transplants (FMT) from new donors on patients with Ulcerative Colitis. It aims to see if FMT can induce remission and maintain it long-term.

How Is the Trial Designed?

Group I: Open label FMT therapy Experimental Treatment 1 Intervention

FMT from a related or unrelated healthy donor screened for known communicable disease

Fecal Microbiota Transplant is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Fecal Microbiota Transplantation for:

• Recurrent and refractory Clostridioides difficile infection

Approved in European Union as Faecal Microbiota Transplantation for:

• Recurrent and refractory Clostridioides difficile infection

Approved in Canada as Fecal Microbiota Transplantation for:

• Recurrent and refractory Clostridioides difficile infection

Who Is Running the Clinical Trial?

Hamilton Health Sciences Corporation

Lead Sponsor

Trials

380

Recruited

345,000+

Canadian Institutes of Health Research (CIHR)

Collaborator

Trials

1,417

Recruited

26,550,000+

Published Research Related to This Trial

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 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]

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) is well-accepted and tolerated by patients with active ulcerative colitis (UC), with a 78.3% consent rate among 129 patients offered the treatment.

The procedure showed a good safety profile, with common short-term adverse events like abdominal discomfort and flatulence, while long-term adverse events were relatively rare, indicating that FMT could be a promising therapy for managing UC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acceptability, tolerability, and safety of fecal microbiota transplantation in patients with active ulcerative colitis (AT&S Study). Sood, A., Singh, A., Mahajan, R., et al.[2020]

Fecal microbiota transplantation (FMT) was found to be a well-tolerated and effective treatment for patients with mild-to-moderate ulcerative colitis (UC), showing a higher rate of clinical remission compared to standard care after 8 weeks (84.6% vs. 70.4%).

Patients receiving FMT also experienced a more significant improvement in gut microbiota composition and a greater reduction in the Mayo score, indicating better overall clinical outcomes compared to those on standard mesalazine therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of fecal microbiota transplantation via colonoscopy as add-on therapy in patients with mild-to-moderate ulcerative colitis: A randomized clinical trial. Tkach, S., Dorofeyev, A., Kuzenko, I., 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]

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]

In a study of 15 patients with steroid-dependent ulcerative colitis (UC), a step-up fecal microbiota transplantation (FMT) strategy led to clinical improvement in 57.1% of patients, allowing them to discontinue steroid use.

The successful treatment was associated with significant changes in gut microbiota composition, resembling that of the donor, and no severe adverse events were reported, indicating the safety of this approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Step-up fecal microbiota transplantation strategy: a pilot study for steroid-dependent ulcerative colitis. Cui, B., Li, P., Xu, L., 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9802301/

Fecal Microbiota Transplantation for Ulcerative Colitis Fecal microbiota transplantation (FMT) is currently an approved treatment for recurrent and refractory Clostridioides difficile infection.

2. discoveries.vanderbilthealth.com discoveries.vanderbilthealth.com/2024/03/fecal-transplant-outcomes-in-ulcerative-colitis-crohns/

Fecal Transplant Outcomes in Ulcerative Colitis, Crohn's The most definitive finding was FMT reduced colonic inflammation in UC assessed at a 6-to-12-week follow-up, inducing clinical and endoscopic ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S1542356524009078

Gut Microbiota Features in Relation to Fecal ... Fecal microbiota transplantation (FMT) can induce remission in patients with ulcerative colitis, yet its efficacy needs improvement.

4. academic.oup.com academic.oup.com/ibdjournal/article/31/9/2408/8008973

Guidance for Fecal Microbiota Transplantation Trials in ... Despite its promise, the effectiveness of FMT for treating IBD, particularly for ulcerative colitis (UC), still requires thorough clinical ...

5. nature.com nature.com/articles/s41598-023-41182-6

Efficacy and safety of fecal microbiota transplantation in the ... Fecal microbiota transplantation has shown potential as a therapeutic intervention for inducing clinical remission in ulcerative colitis UC.

6. ghadvances.org ghadvances.org/article/S2772-5723(25)00128-1/fulltext

Fecal Microbiota Transplantation Induces Sustained Gut ... FMT induces sustained changes in the pediatric UC gut microbiome, with distinct microbial signatures associated with disease severity and clinical outcomes.