Fecal Microbial Transplantation for Rheumatoid Arthritis
(FeMiTRA Trial)
Recruiting in Palo Alto (17 mi)
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?
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.12678
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.910111213
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
See 3 more
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.
See 15 more
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 OverviewThe 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
2Treatment groups
Experimental Treatment
Placebo Group
Group I: Fecal Microbial TransplantExperimental Treatment1 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: PlaceboPlacebo Group1 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
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
St. Joseph's Health Care LondonLondon, Canada
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Who Is Running the Clinical Trial?
Lawson Health Research InstituteLead Sponsor
London Health Sciences Centre Research Institute and Lawson Research Institute of St. Joseph'sLead Sponsor
London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph'sLead Sponsor
London Health Sciences Centre OR Lawson Research Institute of St. Joseph'sLead Sponsor
St. Joseph's Health Care LondonCollaborator
References
Fecal microbiota transplantation for rheumatoid arthritis: A case report. [2021]No previous case of using fecal microbiota transplantation (FMT) to treat rheumatoid arthritis (RA) has been reported. 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.
Experiences and perceptions of patients with psoriatic arthritis participating in a trial of faecal microbiota transplantation: a nested qualitative study. [2021]Patients' first-hand experiences of faecal microbiota transplantation (FMT) performed in a rheumatological care setting have yet to be elucidated. The objectives were to explore participants' perceptions of being part of an FMT trial thereby identifying potential trial participation effects and enlightening the patient perspective on the outlook for future FMT trials in rheumatic diseases.
Therapeutic alteration of the microbiota in rheumatic diseases: Hype or potential? [2023]Multiple studies have demonstrated abnormalities in the contents of the fecal microbiota in patients with a variety of forms of arthritis. This has prompted interest in microbial-altering therapy as a therapeutic tool. While antibiotics as a long-term therapeutic tool have largely fallen out of favor, there have been multiple studies evaluating probiotics in rheumatoid arthritis, spondyloarthritis, or systemic sclerosis; a small number of studies have tested fecal microbial transplantation (FMT) in rheumatic diseases. Although probiotics were well tolerated, few studies detected meaningful clinical benefit regardless of indication. Likewise, one of the two randomized studies evaluating FMT showed minimal clinical benefit, while the other demonstrated worsening compared to sham treatment. In this review article, I summarize the literature on probiotics and FMT in rheumatic diseases, discuss potential reasons for the absence of demonstrable benefit, and suggest avenues of future direction of research.
Case report: Fecal microbiota transplantation in refractory ankylosing spondylitis. [2023]Ankylosing spondylitis (AS) is the prototype of a group of systemic inflammatory diseases referred to as spondyloarthritis. Comorbid inflammatory bowel disease and changed gut microbiota in AS have attracted attention to the influence of gut-joint axis and encouraged treating AS by targeting gut microbiota. Here we first reported a patient with refractory AS and comorbid ulcerative colitis (UC) who underwent three fecal microbiota transplantations (FMTs). Inadequate response to conventional treatments including tumor necrosis factor inhibitors impelled FMT as alternative therapy. Notable improvements in AS and UC accompanied with changed fecal microbiota were recorded at 1 week post-FMT1. Further recovery was found after the other two FMTs, and a roughly stable status was maintained in the follow-up period. More studies are needed to validate the effectiveness of FMT in AS and its mechanisms.
Efficacy and safety of faecal microbiota transplantation in patients with psoriatic arthritis: protocol for a 6-month, double-blind, randomised, placebo-controlled trial. [2019]An unbalanced intestinal microbiota may mediate activation of the inflammatory pathways seen in psoriatic arthritis (PsA). A randomised, placebo-controlled trial of faecal microbiota transplantation (FMT) infused into the small intestine of patients with PsA with active peripheral disease who are non-responsive to methotrexate (MTX) treatment will be conducted. The objective is to explore clinical aspects associated with FMT performed in patients with PsA.
[Current research progress and thinking of fecal microbiota transplantation for the treatment of gastrointestinal disorders]. [2020]Fecal microbiota transplantation (FMT), also known as fecal bacteriotherapy or fecal infusion, consists of injection of a liquid filtrate of feces from a healthy donor into the gastrointestinal tract of a recipient individual. FMT has been proposed as a therapeutic approach for functional diseases of the gastrointestinal tract by reestablishment of a wide diversity of intestinal flora. Clostridium difficile infection (CDI) treatment guideline from American Gastroenterology Association (AGA) recommends that FMT can be used as the treatment protocols of relapse CDI. Numerous case reports, retrospective case series, and randomized controlled trials have shown the benefit of FMT in patients with functional bowel disorders, including inflammatory bowel disease, irritable bowel syndrome and constipation, etc. Evidence regarding the safety of FMT is relatively limited because the very rapid adoption of FMT as a therapeutic modality for CDI occurred before the performance of large, long prospective trials that are typically conducted to assess the safety of new interventions. Potential adverse events can be categorized as short-term and long-term, and short-term events can further be divided into those related to the method of FMT delivery (colonoscopy, sedation) and those related to the FMT itself. Due to the recent emergence of FMT, little data exist regarding long-term events and many safety concerns are speculative. Capsulized FMT therapy solves the clinical problems associated with the use of fresh FMT suspensions for long-term maintenance i.e. repeat transplantation and invasive procedures, which is of great significance to optimize the traditional FMT clinical strategy. Future work will focus on establishing best practices and more robust safety data than exist currently, as well as refining FMT beyond current "whole-stool" transplants to increase safety and tolerability. Encapsulated formulations, full-spectrum stool-based products, and defined microbial consortia are all in the immediate future. Although challenges exist, regulatory agencies have been willing to work with stakeholders and will continue to evolve and adapt policy as therapeutics based on human gut microbiota research emerge.
Regulation, risk and safety of Faecal Microbiota Transplant. [2021]From its origins as a left-field, experimental, and even "maverick" intervention, faecal microbiota transplantation (FMT) is now a well-recognised, accepted, and potentially life-saving therapeutic strategy, for the management of recurrent Clostridiodes difficile infection (rCDI). It is being investigated as a treatment for a growing number of diseases including hepatic encephalopathy and eradication of antimicrobial resistant organisms, and the list of indications will likely expand in the future. There is no universally accepted definition of what FMT is, and its mechanism of action remains incompletely understood; this has likely contributed to the breadth of approaches to regulation depending on interpretation. In the UK FMT is considered a medicinal product, in North America, a biological product, whereas in parts of Europe, it is considered a human cell/tissue product. Regulation seeks to improve quality and safety, however, lack of standardisation creates confusion, and overly restrictive regulation may hamper widespread access and discourage research using FMT. FMT is generally considered safe, especially if rigorous donor screening and testing is conducted. Most short-term risks are associated with the delivery method (e.g. colonoscopy). Longer term risks are less well described but longitudinal follow-up of treated cohorts is in place to assess for this, and no signal towards harm has been found to date. Rarely it has been associated with adverse outcomes including the transmission of antibiotic resistant bacteria, and even death. It is vital patients undergoing FMT are well informed to the currently appreciated risks and benefits before proceeding.
Multidonor intensive faecal microbiota transplantation for active ulcerative colitis: a randomised placebo-controlled trial. [2022]The intestinal microbiota is implicated in the pathogenesis of ulcerative colitis. Faecal microbiota transplantation is a novel form of therapeutic microbial manipulation, but its efficacy in ulcerative colitis is uncertain. We aimed to establish the efficacy of intensive-dosing, multidonor, faecal microbiota transplantation in active ulcerative colitis.
Future strategies in hematopoietic stem cell transplantation for rheumatoid arthritis. [2007]Patients with coincidental rheumatoid arthritis (RA) treated by allogeneic hematopoietic stem cell transplantation (HSCT) for drug induced aplastic anemia have been fortuitously cured of RA. Other than these examples with allogeneic HSCT, there is no known curative therapy for RA. Despite its potential to cure, allogeneic transplantation is not being offered to patients with RA due to transplant related mortality. Advances in HSCT conditioning regimens and better prevention of graft-versus-host disease should allow consideration of allogeneic HSCT as therapy for severe RA. We propose a new, well tolerated, nonmyeloablative allogeneic stem cell transplant regimen as treatment for RA.
Biologic agents in rheumatoid arthritis: an update for managed care professionals. [2023]Rheumatoid arthritis (RA) is a chronic, systemic autoimmune inflammatory arthritis that clinically manifests as joint pain, stiffness, and swelling. If left untreated, persistent synovial inflammation can progress to cartilage and bone destruction and ultimately to major long-term disability and mortality. Synthetic disease-modifying antirheumatic drugs (DMARDs), such as methotrexate, leflunomide, and sulfasalazine, have markedly improved clinical symptoms and slowed joint damage in RA patients. However, despite the effectiveness of synthetic DMARDs, many patients who use them continue to have clinical symptoms of inflammation and progressive joint destruction. Recent advances in our understanding of the pathogenesis of RA have led to the identification of novel cellular and molecular therapeutic targets. Biologic agents aimed at these targets have provided some evidence of effectiveness that is transforming the management of RA.
Apparent cure of rheumatoid arthritis by bone marrow transplantation. [2016]We describe the induction of sustained remissions and possible cure of severe erosive rheumatoid arthritis (RA) by bone marrow transplantation (BMT) in 2 patients. BMT was used to treat severe aplastic anemia which was caused by gold in one case and D-penicillamine in the other. In the 8 and 6 years since the transplants (representing 8 and 4 years since cessation of all immunosuppressive therapy, respectively), the RA in each case has been completely quiescent. Although short term remission of severe RA following BMT has been reported, these are the first cases for which prolonged followup has been available. This experience raises the question of the role of BMT itself as a therapeutic option for patients with uncontrolled destructive synovitis.
Allogeneic intra-bone marrow transplantation prevents rheumatoid arthritis in SKG/Jcl mice. [2010]The treatment of autoimmune diseases by allogeneic bone marrow transplantation remains a promising therapeutic avenue. However, more intensive studies on murine models are essential before application to a large number of human patients. In particular, the use of bone marrow transplantation to treat rheumatoid arthritis has been problematic. We have taken advantage of the SKG/Jcl mouse that develops a chronic T cell-mediated autoimmune disease that mimics rheumatoid arthritis which attempted to prevent the development of immunopathology in these mice by allogeneic bone marrow transplantation (BMT). In particular, we utilized our unique technology in which bone marrow cells (BMCs) of control C57BL/6J mice are directly injected into the bone marrow cavity in the tibia of SKG mice (intra-bone marrow [IBM]-BMT). As controls, SKG/Jcl mice were transplanted with whole BMCs from syngeneic SKG mice. Importantly, 12 months after IBM-BMT [B6-->SKG] demonstrated no evidence of arthritis, whereas the control [SKG-->SKG] mice demonstrated, the expected immunopathology of a rheumatoid arthritis-like condition. Further, hematolymphoid cells in [B6-->SKG] mice were reconstituted by donor-derived cells and the percentages of Treg (Foxp3+/CD4+) cells, the percentages of receptor activator of nuclear factor-kappaB ligand (RANKL)+ cells on the CD4+ T cells and the serum levels of tumor necrosis factor-alpha, interleukin-1 and interleukin-6 were normalized in the [B6-->SKG] mice. These data suggest that IBM-BMT is a viable method of immunological manipulation that suppresses the severe joint destruction and bone absorption in SKG/Jcl mice and lends further credence to the use of this methodology in humans with intractable rheumatoid arthritis.
Nonmyeloablative allogeneic hematopoietic cell transplants: any role for rheumatoid arthritis? [2021]Recent studies have suggested limited efficacy of high dose cyclophosphamide and autologous stem cell transplant as a treatment for severe rheumatoid arthritis. Preclinical data and anecdotal evidence from human transplants suggest that greater efficacy and possible cures might be achieved through use of allogeneic transplants. Newer less intensive methods of allogeneic transplantation have been introduced that reduce morbidity and mortality of the procedure. This article reviews the possible role of the so-called nonmyeloablative transplants in the treatnent of RA.