FMT for MS Patients (MS-FMT)

• ClinicalTrials.gov Identifier: NCT04150549
• Recruitment Status: Not yet recruiting
• First Posted: November 4, 2019
• Last Update Posted: October 25, 2022
• Sponsor: Lawson Health Research Institute
• Information provided by (Responsible Party): Michael Silverman, MD, Lawson Health Research Institute

Tracking Information

• First Submitted Date: October 11, 2019
• First Posted Date: November 4, 2019
• Last Update Posted Date: October 25, 2022
• Estimated Study Start Date: June 2023
• Estimated Primary Completion Date: May 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 1, 2019)

Changes in T2 Lesions - MRI [ Time Frame: Baseline, 6 weeks, 12 months ]

Assess the number of new/enlarging/gad enhancing T2 lesions. We will be comparing baseline to 6 weeks and 6 weeks to 12 months.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: November 1, 2019)

• Blood Brain Barrier - MRI [ Time Frame: Baseline, 6 weeks, 12 months ]
  We will assess the integrity of the blood brain barrier through MRI from baseline to 6 weeks and 6 weeks to 12 months.
• Neurofilament Light Serum Levels [ Time Frame: Baseline, 6 weeks, 3 months, 12 months ]
  As a biomarker of neuronal damage neurofilament light chain levels will be detected. Peripheral blood will be collected in appropriate tubes at baseline, 6 weeks, 3 months and 12 months and processed for serum. Once collected all samples will be sent to the University of Ottawa where a Simoa NfL assay will be undertaken on their Simoa Analyzer. Patients with multiple sclerosis have been shown to have increased intestinal permeability, likely due to a reduction in butyrate-producing bacteria. A decrease in butyrate producing bacteria has been shown to be associated with increased intestinal permeability. Relapsing-remitting MS patients have been shown to have increased intestinal permeability, which may allow dietary and microbial antigens from the intestinal lumen to pass into the blood stream and cause autoimmune responses in MS patients. This may prime the immune system to develop a humoral response to certain bacteria.
• Intestinal Permeability [ Time Frame: Baseline, 6 weeks, 12 months ]
  Small Intestine Permeability: Mannitol/Lactulose administration will be used and urine will be collected to measure small intestine permeability. For small intestine permeability patients will be instructed to drink lactulose solution and collect the urine throughout the night and first thing in the morning. A proper collecting bottle will be provided. Once the urine sample bottle reaches the laboratory University Hospital the total volume will be measured and an aliquot of 30mL total, 10mL in each sterile urine container (no other additives) will be separated and stored at -20C and sent on dry ice to Dr. Meddings laboratory at Calgary, Alberta. All biological material will be transported according to biosafety regulations.
• IgA Microbiota [ Time Frame: Baseline, 3 weeks, 6 weeks, and 12 months ]
  IgA Microbiota analysis: IgA bound bacteria will be detected and sorted (magnetic beads or flow cytometry) using anti-IgA (pan-IgA, detect monomer and secreted multimer (Miltenyi clone: IS11-8E10). Sorted IgA bound bacteria will be stored, and the DNA extracted in one batch at the end of the study. Changes in the composition of IgA bound bacteria for each patient will be determined using the previously mentioned methods. (Rojas, et al. 2018; Planer, et al. 2016)
• Stool Microbiome [ Time Frame: Baseline, 3 weeks, 6 weeks, 3 months, 6 months, 12 months ]
  Gut microbiota analysis before and after FMT: Toilet paper samples will be collected from patients' at baseline and 1-2 days before each scheduled appointment (Al et al. 2018). Patients will store the toilet paper inside of DNA free plastic bags and keep them at 4 °C in the refrigerator until the time of their appointment (alternatively, the samples can be mailed in to the lab, but one method must be chosen for all of the samples collected). Toilet paper samples will be collected from the FMT donor every time they drop off a stool sample for donation. DNA from the toilet paper samples will be extracted in one batch at the end of the study and sent for Illumina Mi-Seq next-generation sequencing of the V4 region of the 16S rRNA gene. Changes in the composition of gut bacteria will be determined using custom R scripts.
• Metabolomics [ Time Frame: Baseline, 3 weeks, 6 weeks, 3 months, 6 months, 12 months ]
  Metabolomics: Serum will be collected for metabolomic analysis. Metabolomics can be used to identify biomarkers of MS and may provide us with information about which patients are more likely to respond to FMT therapy. Butyrate producing bacteria have been shown to be in lower relative abundance in MS patients and concentrations of short-chain fatty acids in stool and will be investigated before and after FMT.
• Metabolomics [ Time Frame: Baseline, 3 weeks, 6 weeks, 3 months, 6 months, 12 months ]
  Metabolomics: Urine will be collected for metabolomic analysis. Metabolomics can be used to identify biomarkers of MS and may provide us with information about which patients are more likely to respond to FMT therapy. Butyrate producing bacteria have been shown to be in lower relative abundance in MS patients and concentrations of short-chain fatty acids in stool and will be investigated before and after FMT.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: FMT for MS Patients
• Official Title: Fecal Microbial Transplantation for Relapsing Multiple Sclerosis Patients - a Placebo-controlled, Double-blinded, Randomized Trial
• Brief Summary: This is a placebo-controlled, double-blinded, randomized trial design, whereby all patients are eligible to start an injectable therapy, and then randomized to either placebo or FMT for approximately 1 year.

Detailed Description

Fecal Microbiome Transplants: Patients will undergo pretreatment with Amoxicillin/Clavulinate (or matched placebo) for 5 days followed by a bowel cleanse with PEGLYTE. Patients will undergo allogeneic or autologous fecal transplants. Patients will be dosed with FMT oral capsules approximately 48 hours after antibiotic treatment has stopped. Following the FMT capsule treatment on day 1, patients will be administered a repeat oral capsule or placebo dose at 3 weeks. Oral omeprazole or omeprazole placebo will be given 1 hour prior to the baseline and 3 week dose. This will be done to ensure full engraftment of the transplant.

Participants will be seen at baseline, 3 weeks, 6 weeks, 3 months, 6 months and 12 months. A series of neurological tests will be performed for safety measures. In addition to this, MRIs will be completed at baseline, 6 weeks and 12 months. Blood, urine and stool samples will also be collected for data analysis and safety measures.

• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Basic Science
• Condition: Multiple Sclerosis

Intervention

• Biological: Fecal Microbial Transplants
  Healthy donor stool will be processed and placed into capsules.
• Biological: Fecal Microbial Transplants
  Participants stool will be processed and placed into capsules.

Study Arms

• Placebo Comparator: Autologous Transplants
  Intervention: Biological: Fecal Microbial Transplants
• Active Comparator: Allogeneic Transplants
  Intervention: Biological: Fecal Microbial Transplants

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Not yet recruiting
• Estimated Enrollment (submitted: November 1, 2019): 34
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: August 2025
• Estimated Primary Completion Date: May 2025 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• 18 - 55 years of age
• Have an expanded disability status scale (EDSS) of < 6
• Have a diagnosis of relapsing multiple sclerosis
• Have evidence of radiographic activity within the 12 months on MRI (new/enlarging T2 lesion or gadolinium enhancing lesion)
• Eligible to start/starting an injectable DMT
• Not on a DMT currently and/or not on a DMT in last 6 months
• Ability to swallow capsules

Exclusion Criteria:

• Unable to provide informed consent
• Does not pass the standard MRI screening questionnaire
• Other disease that can affect GI permeability (such as Inflammatory Bowel Disease, Crohn's disease, ulcerative colitis, indeterminate colitis or microscopic colitis, celiac disease)
• Expected requirement for antibiotics within 3 months (chronic suppressive therapies, elective prosthetic joint insertion)
• Toxic megacolon, small bowel ileus
• Penicillin allergy
• Omeprazole allergy

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 55 Years (Adult)
• Accepts Healthy Volunteers: No
• Listed Location Countries: Not Provided

Administrative Information

• NCT Number: NCT04150549
• Other Study ID Numbers: MS-FMT 002
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Michael Silverman, MD, Lawson Health Research Institute
• Original Responsible Party: Same as current
• Current Study Sponsor: Lawson Health Research Institute
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Lawson Health Research Institute
• Verification Date: October 2022