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Fecal Microbial Transplantation for Rheumatoid Arthritis Trial (FeMiTRA)

Primary Purpose

Arthritis, Arthritis, Rheumatoid, Fecal Microbiota Transplantation

Status
Not yet recruiting
Phase
Not Applicable
Locations
Study Type
Interventional
Intervention
Fecal Microbial transplant
Placebo capsules
Sponsored by
Lawson Health Research Institute
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Arthritis focused on measuring Arthritis, Rheumatoid, Rheumatoid Arthritis, clinical trial, fecal matter transplantation, fecal matter transplant, faecal, autoimmune, proof of concept

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    Placebo Comparator

    Arm Label

    Fecal Microbial Transplant

    Placebo

    Arm Description

    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.

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

    Outcomes

    Primary Outcome Measures

    Change in Intestinal Permeability
    A blood sample will be collected for bacterial DNA analysis.
    Change in Intestinal Permeability
    A urine sample will be collected to measure the lactulose to mannitol ratio.
    Change in RA-associated autoantibodies
    A blood sample will be collected to measure RA-associated autoantibodies.
    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.
    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.
    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.
    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.

    Secondary Outcome Measures

    Change in Fecal Microbial Composition
    Stool samples will be collected to determine fecal microbial composition using 16S-RNA sequencing.
    Change in C-Reactive Protein
    Blood sample will be collected to measure CRP levels.

    Full Information

    First Posted
    February 15, 2023
    Last Updated
    June 1, 2023
    Sponsor
    Lawson Health Research Institute
    Collaborators
    St. Joseph's Health Care London
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    1. Study Identification

    Unique Protocol Identification Number
    NCT05790356
    Brief Title
    Fecal Microbial Transplantation for Rheumatoid Arthritis Trial
    Acronym
    FeMiTRA
    Official Title
    Fecal Microbial Transplantation for Rheumatoid Arthritis Trial
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    June 2023
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    July 1, 2023 (Anticipated)
    Primary Completion Date
    October 1, 2024 (Anticipated)
    Study Completion Date
    April 1, 2025 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Lawson Health Research Institute
    Collaborators
    St. Joseph's Health Care London

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    No
    Data Monitoring Committee
    No

    5. 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.
    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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Arthritis, Arthritis, Rheumatoid, Fecal Microbiota Transplantation
    Keywords
    Arthritis, Rheumatoid, Rheumatoid Arthritis, clinical trial, fecal matter transplantation, fecal matter transplant, faecal, autoimmune, proof of concept

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Not Applicable
    Interventional Study Model
    Parallel Assignment
    Model Description
    Randomized, double-blind, placebo-controlled proof-of-concept study.
    Masking
    ParticipantInvestigator
    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.
    Allocation
    Randomized
    Enrollment
    30 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Fecal Microbial Transplant
    Arm Type
    Experimental
    Arm Description
    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.
    Arm Title
    Placebo
    Arm Type
    Placebo Comparator
    Arm Description
    Participants will be administered 35-40 placebo capsules orally with water. This will only occur once and takes approximately 30 minutes.
    Intervention Type
    Drug
    Intervention Name(s)
    Fecal Microbial transplant
    Intervention Description
    Fecal microbial transplant will be investigated for its effect on gut bacterial composition in patients with rheumatoid arthritis.
    Intervention Type
    Other
    Intervention Name(s)
    Placebo capsules
    Intervention Description
    The placebo capsules will not contain FMT but will have the same appearance.
    Primary Outcome Measure Information:
    Title
    Change in Intestinal Permeability
    Description
    A blood sample will be collected for bacterial DNA analysis.
    Time Frame
    Baseline and 6 weeks
    Title
    Change in Intestinal Permeability
    Description
    A urine sample will be collected to measure the lactulose to mannitol ratio.
    Time Frame
    Baseline and 6 weeks
    Title
    Change in RA-associated autoantibodies
    Description
    A blood sample will be collected to measure RA-associated autoantibodies.
    Time Frame
    Baseline, 6 weeks and 12 weeks
    Title
    Adverse Events
    Description
    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.
    Time Frame
    Baseline
    Title
    Adverse Events
    Description
    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.
    Time Frame
    FMT treatment visit
    Title
    Adverse Events
    Description
    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.
    Time Frame
    6 weeks post-treatment
    Title
    Adverse Events
    Description
    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.
    Time Frame
    12 weeks post-treatment
    Secondary Outcome Measure Information:
    Title
    Change in Fecal Microbial Composition
    Description
    Stool samples will be collected to determine fecal microbial composition using 16S-RNA sequencing.
    Time Frame
    Baseline, 6 weeks and 12 weeks
    Title
    Change in C-Reactive Protein
    Description
    Blood sample will be collected to measure CRP levels.
    Time Frame
    Baseline, 6 weeks and 12 weeks.
    Other Pre-specified Outcome Measures:
    Title
    Pain Visual Analog Scale
    Description
    Change in pain will be measured using a visual analog scale.
    Time Frame
    Baseline, 6 weeks and 12 weeks
    Title
    Fatigue
    Description
    Change in fatigue will be measured with a visual analog scale.
    Time Frame
    Baseline, 6 weeks and 12 weeks
    Title
    Sleep
    Description
    Change in sleep will be measured with a visual analog scale.
    Time Frame
    Baseline, 6 weeks and 12 weeks
    Title
    Change in RA disease activity
    Description
    RA disease activity will be measured using the disease activity score-28 (DAS28).
    Time Frame
    Baseline, 6 weeks and 12 weeks
    Title
    Change in RA disease activity
    Description
    RA disease activity will be measured using the health assessment questionnaire (HAQ).
    Time Frame
    Baseline, 6 weeks and 12 weeks
    Title
    Change in RA disease activity
    Description
    RA disease activity will be measured using the clinical disease activity index (CDAI).
    Time Frame
    Baseline, 6 weeks and 12 weeks
    Title
    Insulin Resistance
    Description
    Fasting glucose and insulin will be measured from a blood sample to calculate the Homeostatic Model Assessment for Insulin Resistance (HOMA-IR).
    Time Frame
    Baseline, 6 weeks and 12 weeks
    Title
    Blood Pressure
    Description
    Systolic and Diastolic blood pressure is part of the standard of care and will be measured at each study visit.
    Time Frame
    Baseline, 6 weeks and 12 weeks
    Title
    Body Mass Index
    Description
    Body mass index is part of the standard of care and will be measured at each study visit.
    Time Frame
    Baseline, 6 weeks and 12 weeks
    Title
    Patient Acceptability of FMT
    Description
    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"
    Time Frame
    Baseline, 6 weeks and 12 weeks
    Title
    Tolerability of DMARD Therapy
    Description
    Participants will complete a survey on tolerability of DMARD therapy.
    Time Frame
    Baseline, 6 weeks and 12 weeks

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    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.
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Lillian Barra, MD, MPH
    Phone
    519-646-6100
    Ext
    65986
    Email
    Lillian.Barra@sjhc.london.on.ca
    First Name & Middle Initial & Last Name or Official Title & Degree
    Jeremy Burton, PhD
    Phone
    519-646-6100
    Ext
    61365
    Email
    jeremy.burton@LawsonResearch.com
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Lillian Barra, MD, MPH
    Organizational Affiliation
    Lawson Health Research Institute
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

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    Fecal Microbial Transplantation for Rheumatoid Arthritis Trial

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