FMT for MS Patients (MS-FMT)
Fecal Microbial Transplantation for Relapsing Multiple Sclerosis Patients - a Placebo-controlled, Double-blinded, Randomized Trial
調査の概要
詳細な説明
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.
研究の種類
入学 (予想される)
段階
- フェーズ2
参加基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
説明
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
研究計画
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：基礎科学
- 割り当て：ランダム化
- 介入モデル：並列代入
- マスキング：ダブル
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
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プラセボコンパレーター：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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アクティブコンパレータ：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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この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Changes in T2 Lesions - MRI
時間枠：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
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Blood Brain Barrier - MRI
時間枠：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.
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Baseline, 6 weeks, 12 months
|
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Neurofilament Light Serum Levels
時間枠：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
時間枠：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
時間枠：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)
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Baseline, 3 weeks, 6 weeks, and 12 months
|
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Stool Microbiome
時間枠：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.
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Baseline, 3 weeks, 6 weeks, 3 months, 6 months, 12 months
|
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Metabolomics
時間枠：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
時間枠：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
|
協力者と研究者
研究記録日
主要日程の研究
研究開始 (予想される)
一次修了 (予想される)
研究の完了 (予想される)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (実際)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
本研究に関する用語
追加の関連 MeSH 用語
その他の研究ID番号
- MS-FMT 002
医薬品およびデバイス情報、研究文書
米国FDA規制医薬品の研究
米国FDA規制機器製品の研究
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