Fecal Microbial Transplantation for Rheumatoid Arthritis Trial

Arthritis, Rheumatoid Clinical Trial

— FeMiTRA  

Official title:

Fecal Microbial Transplantation for Rheumatoid Arthritis Trial

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05790356
• Other study ID #: FeMiTRA01
• Status: Not yet recruiting
• Phase: N/A
• Start date: July 1, 2023
• Est. completion date: April 1, 2025

Study information

• Verified date: June 2023
• Source: Lawson Health Research Institute
• Contact: Lillian Barra, MD, MPH
• Phone: 519-646-6100
• Email: Lillian.Barra[@]sjhc.london.on.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 30
• Est. completion date: April 1, 2025
• Est. primary completion date: October 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Fecal Microbiota Transplantation

Intervention

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

Other:
• Placebo capsules
The placebo capsules will not contain FMT but will have the same appearance.

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Lawson Health Research Institute	St. Joseph's Health Care London

References & Publications (31)

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* Note: There are 31 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Pain Visual Analog Scale	Change in pain will be measured using a visual analog scale.	Baseline, 6 weeks and 12 weeks
Other	Fatigue	Change in fatigue will be measured with a visual analog scale.	Baseline, 6 weeks and 12 weeks
Other	Sleep	Change in sleep will be measured with a visual analog scale.	Baseline, 6 weeks and 12 weeks
Other	Change in RA disease activity	RA disease activity will be measured using the disease activity score-28 (DAS28).	Baseline, 6 weeks and 12 weeks
Other	Change in RA disease activity	RA disease activity will be measured using the health assessment questionnaire (HAQ).	Baseline, 6 weeks and 12 weeks
Other	Change in RA disease activity	RA disease activity will be measured using the clinical disease activity index (CDAI).	Baseline, 6 weeks and 12 weeks
Other	Insulin Resistance	Fasting glucose and insulin will be measured from a blood sample to calculate the Homeostatic Model Assessment for Insulin Resistance (HOMA-IR).	Baseline, 6 weeks and 12 weeks
Other	Blood Pressure	Systolic and Diastolic blood pressure is part of the standard of care and will be measured at each study visit.	Baseline, 6 weeks and 12 weeks
Other	Body Mass Index	Body mass index is part of the standard of care and will be measured at each study visit.	Baseline, 6 weeks and 12 weeks
Other	Patient Acceptability of FMT	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"	Baseline, 6 weeks and 12 weeks
Other	Tolerability of DMARD Therapy	Participants will complete a survey on tolerability of DMARD therapy.	Baseline, 6 weeks and 12 weeks
Primary	Change in Intestinal Permeability	A blood sample will be collected for bacterial DNA analysis.	Baseline and 6 weeks
Primary	Change in Intestinal Permeability	A urine sample will be collected to measure the lactulose to mannitol ratio.	Baseline and 6 weeks
Primary	Change in RA-associated autoantibodies	A blood sample will be collected to measure RA-associated autoantibodies.	Baseline, 6 weeks and 12 weeks
Primary	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
Primary	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
Primary	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
Primary	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	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
Secondary	Change in C-Reactive Protein	Blood sample will be collected to measure CRP levels.	Baseline, 6 weeks and 12 weeks.