Clinical trial NCT05790356: Fecal Microbial Transplantation for Rheumatoid Arthritis Trial
Official title: Fecal Microbial Transplantation for Rheumatoid Arthritis Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Arthritis
Arthritis, Rheumatoid
Fecal Microbiota Transplantation
Keywords: Arthritis
Rheumatoid
Rheumatoid Arthritis
clinical trial
fecal matter transplantation
fecal matter transplant
faecal
autoimmune
proof of concept
Lead sponsor: London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's
Sponsor class: OTHER
Collaborators: name: St. Joseph's Health Care London
First posted: 2023-03-30
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized, double-blind, placebo-controlled proof-of-concept study.
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Change in Intestinal Permeability
timeFrame: Baseline and 6 weeks
measure: Change in Intestinal Permeability
timeFrame: Baseline and 6 weeks
measure: Change in RA-associated autoantibodies
timeFrame: Baseline, 6 weeks and 12 weeks
measure: Adverse Events
timeFrame: Baseline
measure: Adverse Events
timeFrame: FMT treatment visit
measure: Adverse Events
timeFrame: 6 weeks post-treatment
measure: Adverse Events
timeFrame: 12 weeks post-treatment
Secondary outcomes:
measure: Change in Fecal Microbial Composition
timeFrame: Baseline, 6 weeks and 12 weeks
measure: Change in C-Reactive Protein
timeFrame: Baseline, 6 weeks and 12 weeks.
Other outcomes:
measure: Pain Visual Analog Scale
timeFrame: Baseline, 6 weeks and 12 weeks
measure: Fatigue
timeFrame: Baseline, 6 weeks and 12 weeks
measure: Sleep
timeFrame: Baseline, 6 weeks and 12 weeks
measure: Change in RA disease activity
timeFrame: Baseline, 6 weeks and 12 weeks
measure: Change in RA disease activity
timeFrame: Baseline, 6 weeks and 12 weeks
measure: Change in RA disease activity
timeFrame: Baseline, 6 weeks and 12 weeks
measure: Insulin Resistance
timeFrame: Baseline, 6 weeks and 12 weeks
measure: Blood Pressure
timeFrame: Baseline, 6 weeks and 12 weeks
measure: Body Mass Index
timeFrame: Baseline, 6 weeks and 12 weeks
measure: Patient Acceptability of FMT
timeFrame: Baseline, 6 weeks and 12 weeks
measure: Tolerability of DMARD Therapy
timeFrame: Baseline, 6 weeks and 12 weeks
Locations:
city: London
country: Canada
facility: St. Joseph's Health Care London
state: Ontario
Study officials:
affiliation: London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's
name: Lillian Barra, MD, MPH
role: PRINCIPAL_INVESTIGATOR
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