Fecal Microbial Transplantation for Rheumatoid Arthritis Trial

Study Overview
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Brief Summary
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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
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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.

Official Title
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Fecal Microbial Transplantation for Rheumatoid Arthritis Trial

Conditions
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Arthritis, Arthritis, Rheumatoid, Fecal Microbiota Transplantation

Intervention / Treatment
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* Drug: Fecal Microbial transplant
* Other: Placebo capsules


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized, double-blind, placebo-controlled proof-of-concept study.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fecal Microbial Transplant<br>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. | Drug: Fecal Microbial transplant<br>* Fecal microbial transplant will be investigated for its effect on gut bacterial composition in patients with rheumatoid arthritis.<br>|
| Placebo Comparator: Placebo<br>Participants will be administered 35-40 placebo capsules orally with water. This will only occur once and takes approximately 30 minutes. | Other: Placebo capsules<br>* The placebo capsules will not contain FMT but will have the same appearance.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Intestinal Permeability | A blood sample will be collected for bacterial DNA analysis. | Baseline and 6 weeks | 
| Change in Intestinal Permeability | A urine sample will be collected to measure the lactulose to mannitol ratio. | Baseline and 6 weeks | 
| Change in RA-associated autoantibodies | A blood sample will be collected to measure RA-associated autoantibodies. | Baseline, 6 weeks and 12 weeks | 
| Adverse Events | 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. | Baseline | 
| Adverse Events | 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. | FMT treatment visit | 
| Adverse Events | 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. | 6 weeks post-treatment | 
| Adverse Events | 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. | 12 weeks post-treatment | 

Secondary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Arthritis, Rheumatoid, Rheumatoid Arthritis, clinical trial, fecal matter transplantation, fecal matter transplant, faecal, autoimmune, proof of concept