FeMiTRA: Fecal Microbial Transplantation for Rheumatoid Arthritis Trial

Sponsor

Lawson Health Research Institute (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05790356

Collaborator

St. Joseph's Health Care London (Other)

Enrollment

Arms

Anticipated Duration (Months)

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Arthritis Arthritis, Rheumatoid Fecal Microbiota Transplantation	Drug: Fecal Microbial transplant Other: Placebo capsules	Phase 2

Detailed Description

This is a randomized double-blind placebo-controlled phase 2 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 (history and physical exam), 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 Design

Study Type:

Interventional

Anticipated Enrollment :

30 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Randomized, double-blind, placebo-controlled trial.Randomized, double-blind, placebo-controlled trial.

Masking:

Double (Participant, 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.

Primary Purpose:

Treatment

Official Title:

Fecal Microbial Transplantation for Rheumatoid Arthritis Trial

Anticipated Study Start Date :

Apr 1, 2023

Anticipated Primary Completion Date :

Oct 1, 2024

Anticipated Study Completion Date :

Apr 1, 2025

Arms and Interventions

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

Arm

Intervention/Treatment

Experimental: 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.

Drug: Fecal Microbial transplant

Fecal microbial transplant will be investigated for its effect on gut bacterial composition in patients with rheumatoid arthritis.

Placebo Comparator: Placebo

Participants will be administered 35-40 placebo capsules orally with water. This will only occur once and takes approximately 30 minutes.

Other: Placebo capsules

The placebo capsules will not contain FMT but will have the same appearance.

Outcome Measures

Primary Outcome Measures

Change in Intestinal Permeability [Baseline and 6 weeks]
A blood sample will be collected for bacterial DNA analysis.
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 [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.
Adverse Events [FMT treatment visit]
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.
Adverse Events [6 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.
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

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 Outcome Measures

Pain Visual Analog Scale [Baseline, 6 weeks and 12 weeks]
Change in pain will be measured using a visual analog scale.
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).
Change in RA disease activity [Baseline, 6 weeks and 12 weeks]
RA disease activity will be measured using the health assessment questionnaire (HAQ).
Change in RA disease activity [Baseline, 6 weeks and 12 weeks]
RA disease activity will be measured using the clinical disease activity index (CDAI).
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).
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.
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"
Tolerability of DMARD Therapy [Baseline, 6 weeks and 12 weeks]
Participants will complete a survey on tolerability of DMARD therapy.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.