Fecal Microbial Transplantation for Rheumatoid Arthritis Trial

Not Applicable

Recruiting

• Conditions: Arthritis; Arthritis, Rheumatoid; Fecal Microbiota Transplantation
• Interventions: Drug: Fecal Microbial transplant; Other: Placebo capsules

• Registration Number: NCT05790356
• Lead Sponsor: Lawson Health Research Institute

Brief Summary

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

Detailed Description

This is a randomized double-blind placebo-controlled proof-of-concept trial. A total of 30 RA patients will be asked to join the study. They will be randomized to receive capsular FMT + standard of care or placebo + standard of care. There will be four study visits in total: Baseline, FMT administration, 6- and 12-week follow-up visits. Follow-up visits will consist of assessment by a rheumatologist, completion of surveys, and collection of biologic samples.

Samples for the study are stool, urine and blood. Blood and fecal samples will be collected at baseline, 6 weeks and 12 weeks. Urine samples will be collected at baseline and 6 weeks.

Study Timeline

• Study First Submitted: 2023-02-15
• Study First Submitted QC: 2023-03-16
• Study First Posted: 2023-03-30
• Study Start: 2023-08-01
• Status Verified: 2024-08
• Last Update Submitted: 2024-08-19
• Last Update Posted: 2024-08-21
• Primary Completion: 2025-08-01
• Study Completion: 2026-04-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 30

Inclusion Criteria

• 18-years old or older
• RA diagnosis by ACR/EULAR criteria [26]
• Positive for the RA-associated antibodies, anti-citrullinated protein/peptide antibodies (ACPA) and/or rheumatoid factor (RF)
• Stable RA therapy > 6 months
• Patient in remission or low disease activity by DAS28
• Consents to study

Fecal Donor Inclusion Criteria:

• A healthy donor who has a normal body mass index (BMI of 18.5-30) and who satisfies the following criteria will be selected from a pool of donors available in the Infectious Diseases clinic at St. Joseph's Hospital supervised by Dr. Silverman and screened for all transmissible agents. at the Microbiology and Immunology lab at St. Joseph's Hospital under Dr. Silverman for the study and screened for transmissible agents.

Exclusion Criteria

• Pregnant or breastfeeding
• Current or recent [in the last 60 days] exposure to high dose oral (>30 mg of prednisone daily or equivalent), IV corticosteroids, biologic therapies or JAKi.
• Patients who require inhaled steroids or local steroid injections are not excluded from the study
• Has a diagnosis of immunodeficiency (HIV, transplantation, or autoimmune disease other than RA requiring immunosuppressive therapies), or currently receiving systemic steroid therapy (>10 mg prednisone daily or equivalent)
• Received rituximab or other chemotherapeutic agent in the last 2 years.
• Expected to require any other form of systemic or localized anti-neoplastic therapy while on study
• Has a known history of a hematologic malignancy, primary brain tumor or sarcoma, or of another primary solid tumor, unless the patient has undergone potentially curative therapy with no evidence of that disease for five years. NOTE: This time requirement also does not apply to patients who underwent successful definitive resection of basal or squamous cell carcinoma of the skin, superficial bladder cancer, in situ cancers including cervical cancer, breast cancer, melanoma, or other in situ cancers.
• Ongoing use of antibiotics/anti-virals or previous use of antibiotics/anti-virals in the last 3 months prior to the FMT procedure
• Has an active infection requiring systemic therapy or requiring hospital admission in last 3 months.
• Presence of a chronic intestinal disease (e.g. Celiac disease, malabsorption, colonic tumor, IBD)
• Presence of absolute contra-indications to FMT administration
• Toxic megacolon
• Anaphylactic allergic reactions to food (e.g. shellfish, nuts, seafood, eggs)
• Has serious uncontrolled concomitant illnesses, such as: cardiovascular disease (uncontrolled congestive heart failure, hypertension, cardiac ischemia, myocardial infarction, and severe cardiac arrhythmia), severe obstructive or restrictive pulmonary diseases, cirrhosis or ALT>100, renal disease with GFR<50 and uncontrolled psychiatric illness.
• Patient has received a live vaccine within 4 weeks prior to the first dose of treatment
• Insulin-dependent diabetes
• Previous bariatric surgery
• Chronic neutropenia (<0.5) Currently participating in another clinical trial

Fecal Donor Exclusion Criteria:

• Any underlying metabolic disease including; hypertension, hyperlipidemia, diabetes, insulin insensitivity, atherosclerosis
• A history of any gastrointestinal or liver disorders or cancers. Including but not limited to; gastroesophageal reflux, peptic ulcer disease, celiac disease, inflammatory bowel disease (Crohn's disease or ulcerative colitis), microscopic colitis, motility disorders (including gastroparesis and irritable bowel syndrome) diverticular disease
• Previous surgery to the intestine, liver or gallbladder (except remote appendectomy)
• History of any malignancy
• Use within 3 months of any antibiotics
• Hospitalization within 3 months
• Recent travel to a developing country (within 3 months).
• New Sexual Partner (within 3 months)
• Street drug use, family history of diabetes, early onset coronary disease or gastrointestinal or liver disease, colon cancer, familial malignancy
• Psychiatric history (major affective disorder, psychotic illness, ongoing use of any psychiatric medications)
• Any positive laboratory results for a transmissible pathogen
• Alcohol intake with a cut off value of <10g/d in women and <20g/d in men
• Currently participating in another clinical trial that may alter fecal composition.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Fecal Microbial Transplant	Fecal Microbial transplant	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.
Placebo	Placebo capsules	Participants will be administered 35-40 placebo capsules orally with water. This will only occur once and takes approximately 30 minutes.

Primary Outcome Measures

Name	Time	Method
Change in Intestinal Permeability	Baseline and 6 weeks	A urine sample will be collected to measure the lactulose to mannitol ratio.
Change in RA-associated autoantibodies	Baseline, 6 weeks and 12 weeks	A blood sample will be collected to measure RA-associated autoantibodies.
Adverse Events	12 weeks post-treatment	Adverse events will be evaluated at every study visit. Participants will also be instructed to contact study staff by phone if they experience an adverse event in between study visits.

Secondary Outcome Measures

Name	Time	Method
Change in C-Reactive Protein	Baseline, 6 weeks and 12 weeks.	Blood sample will be collected to measure CRP levels.
Change in Fecal Microbial Composition	Baseline, 6 weeks and 12 weeks	Stool samples will be collected to determine fecal microbial composition using 16S-RNA sequencing.

Trial Locations

Locations (1)

St. Joseph's Health Care London; 🇨🇦 London, Ontario, Canada