Fecal Microbial Transplantation for Rheumatoid Arthritis

(FeMiTRA Trial)

Overseen By Jeremy Burton, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Lawson Health Research Institute

Must not be taking: Corticosteroids, Biologics, JAKi, Antibiotics

Disqualifiers: Pregnancy, Immunodeficiency, Cancer, Diabetes, others

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

Duration: 1 day

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether taking capsules with healthy donor stool, known as a fecal microbial transplant (FMT), can help people with rheumatoid arthritis (RA). The aim is to determine if FMT can improve symptoms by balancing gut bacteria in those with RA. Participants will receive either FMT capsules or placebo capsules. This trial may suit individuals diagnosed with RA who are in remission or have low disease activity and have maintained stable RA treatment for over six months. As an unphased trial, this study offers a unique opportunity for patients to contribute to groundbreaking research that could lead to new treatment options for RA.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it requires that your rheumatoid arthritis therapy has been stable for more than 6 months. If you are on high-dose steroids, biologic therapies, or certain other medications, you may not be eligible to participate.

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

Research has shown that fecal microbial transplantation (FMT) is generally safe for treating various conditions, including autoimmune diseases. FMT uses stool samples from healthy donors and is well-tolerated by most patients. A thorough review of existing studies found FMT to be both safe and effective for many diseases, especially those affecting the intestines.

While researchers continue to explore new uses for FMT, such as for rheumatoid arthritis, past safety data remains reassuring. The studies reviewed reported no major safety concerns. However, as with any treatment, monitoring for possible side effects is important to ensure safety. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike traditional treatments for rheumatoid arthritis, which often include medications like NSAIDs, corticosteroids, or biologics targeting the immune system, fecal microbial transplantation (FMT) offers a unique approach by modifying the gut microbiome. Researchers are excited because FMT aims to rebalance gut bacteria, which may reduce inflammation and improve symptoms in a novel way. This method leverages the body's natural microbial communities rather than relying solely on pharmaceuticals, potentially reducing side effects associated with long-term medication use.

What evidence suggests that fecal microbial transplant might be an effective treatment for rheumatoid arthritis?

Research suggests that fecal microbial transplantation (FMT), a treatment under study in this trial, might help treat rheumatoid arthritis (RA). In one case, FMT successfully helped a patient with hard-to-treat RA. FMT involves transferring stool from a healthy donor to balance gut bacteria, which may affect the immune system. Studies have also explored FMT's potential for other autoimmune diseases, indicating it might improve symptoms by altering gut bacteria and immune responses. Early findings suggest FMT could be a promising treatment for RA, but more research is needed to confirm these effects. Participants in this trial will receive either FMT capsules or placebo capsules to evaluate FMT's effectiveness in treating RA. ^{1 2 3 4 6}

Who Is on the Research Team?

Lillian Barra, MD, MPH

Principal Investigator

London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's

Are You a Good Fit for This Trial?

This trial is for adults over 18 with rheumatoid arthritis, who have specific RA antibodies and are in remission or have low disease activity. They must be on stable RA therapy for more than 6 months and agree to the study's terms. A healthy donor with a normal BMI will provide stool samples.

Inclusion Criteria

RA diagnosis by ACR/EULAR criteria

Consents to study

I have antibodies linked to rheumatoid arthritis.

Exclusion Criteria

I have not received a live vaccine in the last 4 weeks.

I have a long-term low white blood cell count.

Anaphylactic allergic reactions to food

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline

Baseline assessments including collection of stool, urine, and blood samples

1 day

1 visit (in-person)

Treatment

Participants receive either FMT or placebo capsules orally

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness with assessments at 6 and 12 weeks

12 weeks

2 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Fecal Microbial transplant
• Placebo capsules

Trial Overview The trial tests if swallowing capsules containing stool from healthy donors (fecal microbial transplant) can benefit rheumatoid arthritis patients compared to placebo capsules without active ingredients.

How Is the Trial Designed?

Group I: Fecal Microbial Transplant Experimental Treatment 1 Intervention

Participants will be administered 35-40 FMT capsules orally with water, for a total dose of 80-100g. This will only occur once and takes approximately 30 minutes.

Group II: Placebo Placebo Group 1 Intervention

Participants will be administered 35-40 placebo capsules orally with water. This will only occur once and takes approximately 30 minutes.

Fecal Microbial transplant is already approved in United States, European Union for the following indications:

Approved in United States as Fecal Microbiota Transplant for:

• Clostridioides difficile infection (CDI)

Approved in European Union as Fecal Microbiota Transplant for:

• Clostridioides difficile infection (CDI)
• Ulcerative colitis

Who Is Running the Clinical Trial?

Lawson Health Research Institute

Lead Sponsor

Trials

684

Recruited

432,000+

London Health Sciences Centre Research Institute and Lawson Research Institute of St. Joseph's

Lead Sponsor

Trials

686

Recruited

427,000+

London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's

Lead Sponsor

Trials

678

Recruited

421,000+

London Health Sciences Centre OR Lawson Research Institute of St. Joseph's

Lead Sponsor

Trials

668

Recruited

424,000+

St. Joseph's Health Care London

Collaborator

Trials

28

Recruited

2,500+

Published Research Related to This Trial

High-dose cyclophosphamide and autologous stem cell transplants have shown limited effectiveness in treating severe rheumatoid arthritis, suggesting a need for alternative approaches.

Allogeneic stem cell transplants, particularly newer nonmyeloablative methods, may offer greater efficacy and lower risks, potentially leading to better outcomes for patients with rheumatoid arthritis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nonmyeloablative allogeneic hematopoietic cell transplants: any role for rheumatoid arthritis? McSweeney, P.[2021]

Patients with psoriatic arthritis (PsA) reported that participating in a trial for faecal microbiota transplantation (FMT) positively influenced their understanding of their condition and improved their everyday lives, highlighting the psychological benefits of trial participation.

The study found that FMT was considered a tolerable and safe treatment by participants, suggesting that it could be a promising option for future research in microbiota-targeted therapies for rheumatic diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Experiences and perceptions of patients with psoriatic arthritis participating in a trial of faecal microbiota transplantation: a nested qualitative study. Kragsnaes, MS., Sødergren, ST., Kjeldsen, J., et al.[2021]

Faecal microbiota transplantation (FMT) is now a recognized and potentially life-saving treatment for recurrent Clostridiodes difficile infection (rCDI) and is being explored for other conditions, although its exact mechanism of action is still not fully understood.

FMT is generally considered safe when conducted with proper donor screening, but there are potential risks, including the rare transmission of antibiotic-resistant bacteria, highlighting the importance of informed consent for patients considering this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Regulation, risk and safety of Faecal Microbiota Transplant. Merrick, B., Allen, L., Masirah M Zain, N., et al.[2021]

A patient with refractory ankylosing spondylitis and ulcerative colitis showed significant improvement after undergoing three fecal microbiota transplantations (FMTs), especially noted one week after the first transplant.

The changes in fecal microbiota correlated with the improvements in both ankylosing spondylitis and ulcerative colitis symptoms, suggesting that targeting gut microbiota may be a promising alternative therapy for AS, although further studies are needed to confirm these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Case report: Fecal microbiota transplantation in refractory ankylosing spondylitis. Wang, L., Wei, Z., Pan, F., et al.[2023]

Allogeneic hematopoietic stem cell transplantation (HSCT) has shown potential to cure rheumatoid arthritis (RA) in patients who received it for drug-induced aplastic anemia, but it is not commonly offered due to risks of transplant-related mortality.

The authors propose a new, nonmyeloablative HSCT regimen that could be safer and better tolerated, making it a viable treatment option for severe RA, especially with advancements in conditioning regimens and graft-versus-host disease prevention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Future strategies in hematopoietic stem cell transplantation for rheumatoid arthritis. Burt, RK., Barr, W., Oyama, Y., et al.[2007]

In a trial involving 85 patients with active ulcerative colitis, faecal microbiota transplantation (FMT) resulted in clinical remission in 27% of patients compared to only 8% in the placebo group, indicating its potential efficacy as a treatment.

The study found that FMT led to increased microbial diversity and specific bacterial changes associated with clinical outcomes, suggesting that FMT not only improves symptoms but also alters the gut microbiome in beneficial ways.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multidonor intensive faecal microbiota transplantation for active ulcerative colitis: a randomised placebo-controlled trial. Paramsothy, S., Kamm, MA., Kaakoush, NO., et al.[2022]

Biologic agents targeting specific inflammatory mediators, such as TNF-alpha, have shown effectiveness in improving clinical outcomes and preventing joint damage in rheumatoid arthritis (RA) patients who do not respond to traditional synthetic DMARDs, with multiple studies supporting the benefits of early treatment.

While biologic therapies can significantly reduce inflammation and improve symptoms, they also carry risks, including increased susceptibility to infections and potential side effects like injection site reactions, necessitating careful patient screening and vaccination before treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biologic agents in rheumatoid arthritis: an update for managed care professionals. Agarwal, SK.[2023]

In a study using SKG/Jcl mice, a model for rheumatoid arthritis, intra-bone marrow transplantation (IBM-BMT) of bone marrow cells from healthy mice successfully prevented the development of arthritis over 12 months, while control mice showed typical disease progression.

The IBM-BMT not only suppressed joint destruction but also normalized immune markers, such as Treg cell percentages and inflammatory cytokine levels, suggesting it could be a promising treatment approach for severe rheumatoid arthritis in humans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Allogeneic intra-bone marrow transplantation prevents rheumatoid arthritis in SKG/Jcl mice. Kushida, T., Ueda, Y., Umeda, M., et al.[2010]

This case report presents the first known instance of using fecal microbiota transplantation (FMT) to treat a patient with refractory rheumatoid arthritis (RA), suggesting a novel therapeutic approach.

The successful treatment indicates that FMT may have a beneficial effect on RA, warranting further investigation into its efficacy and safety for this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fecal microbiota transplantation for rheumatoid arthritis: A case report. Zeng, J., Peng, L., Zheng, W., et al.[2021]

Probiotics have been well tolerated in patients with rheumatic diseases, but most studies have not shown significant clinical benefits from their use.

Fecal microbial transplantation (FMT) has shown mixed results, with one study indicating minimal benefit and another suggesting worsening symptoms compared to sham treatment, highlighting the need for further research in this area.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic alteration of the microbiota in rheumatic diseases: Hype or potential? Stoll, ML.[2023]

This study will investigate the effects of fecal microbiota transplantation (FMT) in 80 patients with psoriatic arthritis (PsA) who are not responding to methotrexate treatment, aiming to assess its efficacy in improving disease activity over a 6-month period.

The trial is designed as a randomized, double-blind, placebo-controlled study, ensuring rigorous evaluation of FMT's safety and effectiveness, with a primary focus on treatment failure rates and monitoring for adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of faecal microbiota transplantation in patients with psoriatic arthritis: protocol for a 6-month, double-blind, randomised, placebo-controlled trial. Kragsnaes, MS., Kjeldsen, J., Horn, HC., et al.[2019]

Bone marrow transplantation (BMT) has led to sustained remission and possible cure of severe erosive rheumatoid arthritis (RA) in two patients, with follow-up periods of 8 and 6 years after the procedure.

These cases suggest that BMT could be a viable long-term treatment option for patients with severe RA, particularly those who have not responded to other therapies, as both patients remained free of RA symptoms long after stopping immunosuppressive therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Apparent cure of rheumatoid arthritis by bone marrow transplantation. Lowenthal, RM., Cohen, ML., Atkinson, K., et al.[2016]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7869316/

Fecal microbiota transplantation for rheumatoid arthritis We report a case of a patient with refractory RA successfully treated with FMT indicating that FMT may have a good therapeutic effect on RA.

2. sciencedirect.com sciencedirect.com/science/article/pii/S0896841123000471

Fecal microbiota transplantation: Emerging applications in ... Fecal microbiota transplantation (FMT) is currently being considered for use in the treatment of various autoimmune diseases.

3. frontiersin.org frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1439176/full

Safety and efficacy of fecal microbiota transplantation (FMT ... This study aims to comprehensively review the current literature on FMT as a modern procedure for treating various diseases.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9562921/

Safety and efficacy of fecal microbiota transplantation for ... The outcomes include clinical symptoms, improvement in biochemistry, improvement in intestinal microbiota, improvement in the immune system, and adverse events.

5. nature.com nature.com/articles/s41522-024-00549-x

Fecal microbiota transplantation influences ... We found that the successful modulation of microbiota composition and functional profiles by FMT from a healthy donor was not associated with the resolution of ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12314702/

The current landscape of fecal microbiota transplantation in ... Long-Term Safety Outcomes of Fecal Microbiota Transplantation: Real-World Data Over 8 Years From the Hong Kong FMT Registry. Clin ...