FMT for MS Patients (MS-FMT)
Fecal Microbial Transplantation for Relapsing Multiple Sclerosis Patients - a Placebo-controlled, Double-blinded, Randomized Trial
研究概览
详细说明
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.
研究类型
注册 (预期的)
阶段
- 阶段2
参与标准
资格标准
适合学习的年龄
接受健康志愿者
有资格学习的性别
描述
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
学习计划
研究是如何设计的？
设计细节
- 主要用途：基础科学
- 分配：随机化
- 介入模型：并行分配
- 屏蔽：双倍的
武器和干预
参与者组/臂 |
干预/治疗 |
|---|---|
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安慰剂比较：Autologous Transplants
|
Healthy donor stool will be processed and placed into capsules.
Participants stool will be processed and placed into capsules.
|
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有源比较器：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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研究衡量的是什么？
主要结果指标
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
|
Changes in T2 Lesions - MRI
大体时间：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.
|
Baseline, 6 weeks, 12 months
|
次要结果测量
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
|
Blood Brain Barrier - MRI
大体时间：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.
|
Baseline, 6 weeks, 12 months
|
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Neurofilament Light Serum Levels
大体时间：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. |
Baseline, 6 weeks, 3 months, 12 months
|
|
Intestinal Permeability
大体时间：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.
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Baseline, 6 weeks, 12 months
|
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IgA Microbiota
大体时间：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)
|
Baseline, 3 weeks, 6 weeks, and 12 months
|
|
Stool Microbiome
大体时间：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.
|
Baseline, 3 weeks, 6 weeks, 3 months, 6 months, 12 months
|
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Metabolomics
大体时间：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.
|
Baseline, 3 weeks, 6 weeks, 3 months, 6 months, 12 months
|
|
Metabolomics
大体时间：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.
|
Baseline, 3 weeks, 6 weeks, 3 months, 6 months, 12 months
|
合作者和调查者
研究记录日期
研究主要日期
学习开始 (预期的)
初级完成 (预期的)
研究完成 (预期的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (实际的)
研究记录更新
最后更新发布 (实际的)
上次提交的符合 QC 标准的更新
最后验证
更多信息
与本研究相关的术语
其他相关的 MeSH 术语
其他研究编号
- MS-FMT 002
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