FMT for MS Patients (MS-FMT)
Fecal Microbial Transplantation for Relapsing Multiple Sclerosis Patients - a Placebo-controlled, Double-blinded, Randomized Trial
A tanulmány áttekintése
Állapot
Körülmények
Beavatkozás / kezelés
Részletes leírás
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.
Tanulmány típusa
Beiratkozás (Várható)
Fázis
- 2. fázis
Részvételi kritériumok
Jogosultsági kritériumok
Tanulmányozható életkorok
Egészséges önkénteseket fogad
Tanulmányozható nemek
Leírás
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
Tanulási terv
Hogyan készül a tanulmány?
Tervezési részletek
- Elsődleges cél: Alapvető tudomány
- Kiosztás: Véletlenszerűsített
- Beavatkozó modell: Párhuzamos hozzárendelés
- Maszkolás: Kettős
Fegyverek és beavatkozások
Résztvevő csoport / kar |
Beavatkozás / kezelés |
|---|---|
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Placebo Comparator: Autologous Transplants
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Healthy donor stool will be processed and placed into capsules.
Participants stool will be processed and placed into capsules.
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Aktív összehasonlító: Allogeneic Transplants
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Healthy donor stool will be processed and placed into capsules.
Participants stool will be processed and placed into capsules.
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Mit mér a tanulmány?
Elsődleges eredményintézkedések
Eredménymérő |
Intézkedés leírása |
Időkeret |
|---|---|---|
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Changes in T2 Lesions - MRI
Időkeret: Baseline, 6 weeks, 12 months
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Assess the number of new/enlarging/gad enhancing T2 lesions.
We will be comparing baseline to 6 weeks and 6 weeks to 12 months.
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Baseline, 6 weeks, 12 months
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Másodlagos eredményintézkedések
Eredménymérő |
Intézkedés leírása |
Időkeret |
|---|---|---|
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Blood Brain Barrier - MRI
Időkeret: Baseline, 6 weeks, 12 months
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We will assess the integrity of the blood brain barrier through MRI from baseline to 6 weeks and 6 weeks to 12 months.
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Baseline, 6 weeks, 12 months
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Neurofilament Light Serum Levels
Időkeret: Baseline, 6 weeks, 3 months, 12 months
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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. |
Baseline, 6 weeks, 3 months, 12 months
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Intestinal Permeability
Időkeret: Baseline, 6 weeks, 12 months
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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.
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Baseline, 6 weeks, 12 months
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IgA Microbiota
Időkeret: Baseline, 3 weeks, 6 weeks, and 12 months
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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)
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Baseline, 3 weeks, 6 weeks, and 12 months
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Stool Microbiome
Időkeret: Baseline, 3 weeks, 6 weeks, 3 months, 6 months, 12 months
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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.
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Baseline, 3 weeks, 6 weeks, 3 months, 6 months, 12 months
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Metabolomics
Időkeret: Baseline, 3 weeks, 6 weeks, 3 months, 6 months, 12 months
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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.
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Baseline, 3 weeks, 6 weeks, 3 months, 6 months, 12 months
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Metabolomics
Időkeret: Baseline, 3 weeks, 6 weeks, 3 months, 6 months, 12 months
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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.
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Baseline, 3 weeks, 6 weeks, 3 months, 6 months, 12 months
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Együttműködők és nyomozók
Szponzor
Tanulmányi rekorddátumok
Tanulmány főbb dátumok
Tanulmány kezdete (Várható)
Elsődleges befejezés (Várható)
A tanulmány befejezése (Várható)
Tanulmányi regisztráció dátumai
Először benyújtva
Először nyújtották be, amely megfelel a minőségbiztosítási kritériumoknak
Első közzététel (Tényleges)
Tanulmányi rekordok frissítései
Utolsó frissítés közzétéve (Tényleges)
Az utolsó frissítés elküldve, amely megfelel a minőségbiztosítási kritériumoknak
Utolsó ellenőrzés
Több információ
A tanulmányhoz kapcsolódó kifejezések
További vonatkozó MeSH feltételek
Egyéb vizsgálati azonosító számok
- MS-FMT 002
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