Fecal Microbial Transplantation for Rheumatoid Arthritis

(FeMiTRA Trial)

Recruiting in Palo Alto (17 mi)

Overseen by Lillian Barra, MD, MPH

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: Lawson Health Research Institute

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

Disqualifiers: Pregnancy, Immunodeficiency, Cancer, Diabetes, others

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

This clinical trial will investigate the effects of capsules containing stool from healthy donors, called fecal microbial transplant (FMT), in rheumatoid arthritis patients.

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.

What data supports the effectiveness of this treatment for rheumatoid arthritis?

There is a case report of a patient with difficult-to-treat rheumatoid arthritis who showed improvement after receiving fecal microbiota transplantation (FMT), suggesting it might be helpful for this condition. ^{1 2 3 4 5}

Is fecal microbiota transplantation (FMT) generally safe for humans?

FMT is generally considered safe, especially with thorough donor screening and testing. Most short-term risks are related to the delivery method, like colonoscopy, while long-term risks are less understood but have not shown harm in follow-ups. Rarely, it has been linked to serious outcomes, such as the transmission of antibiotic-resistant bacteria. ^{1 2 6 7 8}

How does fecal microbial transplantation differ from other treatments for rheumatoid arthritis?

Fecal microbial transplantation (FMT) is unique because it involves transferring stool from a healthy donor to a patient to restore gut bacteria balance, which is different from traditional rheumatoid arthritis treatments that typically involve drugs or biologics targeting the immune system. This approach is novel as it focuses on altering the gut microbiome, which may influence inflammation and immune responses in the body. ^{9 10 11 12 13}

Research Team

Lillian Barra, MD, MPH

Principal Investigator

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

Eligibility Criteria

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

I am 18 years old or older.

RA diagnosis by ACR/EULAR criteria

Consents to study

Exclusion Criteria

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

Anaphylactic allergic reactions to food

I have had weight loss surgery in the past.

Trial Timeline

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)

Treatment Details

Interventions

• Fecal Microbial transplant (Microbiome Therapy)
• Placebo capsules (Other)

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.

Participant Groups

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.

Who Is Running the Clinical Trial?

Lawson Health Research Institute

Lead Sponsor

Trials

684

Recruited

432,000+

Dr. Michael Strong

Lawson Health Research Institute

Chief Medical Officer

MD

Roy Butler

Lawson Health Research Institute

Chief Executive Officer

PhD in Health Sciences

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

Lead Sponsor

Trials

686

Recruited

427,000+

Dr. Alex Barron

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

Chief Medical Officer since 2023

MD from Western University

David Musyj

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

Chief Executive Officer

Physiotherapy degree

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

Lead Sponsor

Trials

678

Recruited

421,000+

Lisa Porter

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

Chief Medical Officer

PhD in Biomedical Sciences

Roy Butler

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

Chief Executive Officer

PhD in Health Sciences

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

Lead Sponsor

Trials

668

Recruited

424,000+

Roy Butler

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

Chief Executive Officer

PhD in Health Sciences

Dr. Cindy Hutnik

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

Chief Medical Officer

MD, PhD

St. Joseph's Health Care London

Collaborator

Trials

28

Recruited

2,500+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Fecal microbiota transplantation for rheumatoid arthritis: A case report. [2021]

2. England 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. [2021]

3. Netherlands pubmed.ncbi.nlm.nih.gov

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

4. Switzerland pubmed.ncbi.nlm.nih.gov

Case report: Fecal microbiota transplantation in refractory ankylosing spondylitis. [2023]

5. England 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. [2019]

6. China pubmed.ncbi.nlm.nih.gov

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

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

Regulation, risk and safety of Faecal Microbiota Transplant. [2021]

8. England pubmed.ncbi.nlm.nih.gov

Multidonor intensive faecal microbiota transplantation for active ulcerative colitis: a randomised placebo-controlled trial. [2022]

9. Canada pubmed.ncbi.nlm.nih.gov

Future strategies in hematopoietic stem cell transplantation for rheumatoid arthritis. [2007]

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

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

11. Canada pubmed.ncbi.nlm.nih.gov

Apparent cure of rheumatoid arthritis by bone marrow transplantation. [2016]

12. England pubmed.ncbi.nlm.nih.gov

Allogeneic intra-bone marrow transplantation prevents rheumatoid arthritis in SKG/Jcl mice. [2010]

13. Canada pubmed.ncbi.nlm.nih.gov

Nonmyeloablative allogeneic hematopoietic cell transplants: any role for rheumatoid arthritis? [2021]