Arthritis, Arthritis, Rheumatoid, Fecal Microbiota Transplantation
Conditions
Keywords
Arthritis, Rheumatoid, Rheumatoid Arthritis, clinical trial, fecal matter transplantation, fecal matter transplant, faecal, autoimmune, proof of concept
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.
Interventions
Fecal microbial transplant will be investigated for its effect on gut bacterial composition in patients with rheumatoid arthritis.
OTHERPlacebo capsules
The placebo capsules will not contain FMT but will have the same appearance.
Sponsors
St. Joseph's Health Care London
London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
Neither the participants or the investigator will know which treatment arms participants have been assigned to. This information can be obtained quickly from pharmacy if needed.
Intervention model description
Randomized, double-blind, placebo-controlled proof-of-concept study.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Intestinal Permeability | Baseline and 6 weeks | A blood sample will be collected for bacterial DNA analysis. |
| Change in RA-associated autoantibodies | Baseline, 6 weeks and 12 weeks | A blood sample will be collected to measure RA-associated autoantibodies. |
| Adverse Events | Baseline | 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| Change in C-Reactive Protein | Baseline, 6 weeks and 12 weeks. | Blood sample will be collected to measure CRP levels. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Blood Pressure | Baseline, 6 weeks and 12 weeks | Systolic and Diastolic blood pressure is part of the standard of care and will be measured at each study visit. |
| Body Mass Index | Baseline, 6 weeks and 12 weeks | Body mass index is part of the standard of care and will be measured at each study visit. |
| Pain Visual Analog Scale | Baseline, 6 weeks and 12 weeks | Change in pain will be measured using a visual analog scale. |
| Tolerability of DMARD Therapy | Baseline, 6 weeks and 12 weeks | Participants will complete a survey on tolerability of DMARD therapy. |
| Patient Acceptability of FMT | Baseline, 6 weeks and 12 weeks | Participants will complete an acceptability of therapy survey for FMT. The survey asks them questions about how well the FMT process was explained to them, and how they feel about it. The participant is asked to select one answer per question ranging from :strongly agree to strongly disagree |
| Fatigue | Baseline, 6 weeks and 12 weeks | Change in fatigue will be measured with a visual analog scale. |
| Sleep | Baseline, 6 weeks and 12 weeks | Change in sleep will be measured with a visual analog scale. |
| Change in RA disease activity | Baseline, 6 weeks and 12 weeks | RA disease activity will be measured using the disease activity score-28 (DAS28). |
| Insulin Resistance | Baseline, 6 weeks and 12 weeks | Fasting glucose and insulin will be measured from a blood sample to calculate the Homeostatic Model Assessment for Insulin Resistance (HOMA-IR). |
Countries
Canada
Contacts
Primary ContactLillian Barra, MD, MPH
Backup ContactJeremy Burton, PhD
Outcome results
None listed