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Primary Investigator passed away.
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The proposed randomized, open label, with treat as usual control group (standard treatment or any disease modifying drugs), crossover phase II study will be conducted in 40 patients (n=20 per group) with the relapsing forms of multiple sclerosis according to the McDonald 2010 Criteria.
Patients will be randomized into 2 intervention groups. One will receive the FMT from month 1 and for the first 6 months (early intervention group). On the other hand, the other group will be a control group during the first 6 months and will receive the FMT for the last 6 months of the study. Patients will be screened for eligibility based on MS diagnosis and EDSS and if eligible then consented. All qualified patients will not be currently or recently treated with high dose steroids.
At Visit 1, before FMT(fecal microbial transplantation), patients will be evaluated for their vital signs, medical history and concomitant medications. Also before transplantation, patient's stool will be collected to study their microbial profile, blood collected for analysis to evaluate cytokines levels as well as blood DNA bacteria and finally, urinalysis to assess gut permeability (baseline). Other assessments (prior to the first dose of therapy) include an Expanded Disability Status Scale (EDSS), pregnancy test (if applicable), physical exam and ECG. Blood samples are also taken at month 1 in order to establish a baseline for routine chemistry/hematology. After all these assessments FMT will be performed by a trained nurse via a rectal enema.
FMT for the early intervention group will be at V1, 2, 2.1, 2.2, V3 and V4. FMT randomized to late intervention group will be V4, 5, 6, 6.1.6.2, 6.3 and V7
Both groups, at Visit 1, Visit 4 and Visit 7, patients will be instructed to drink lactulose solution and collect the urine throughout the previous night and first thing in the morning. A proper collecting bottle will be provided and will also undergo a contrast-enhanced brain MRI scan at Robarts Institute London Ontario.
Those randomized to the Early Intervention group, will return to the clinic for visit 2, 1 month after the first FMT(fecal microbial transplantation). Another stool sample to evaluate the microbial before the second FMT will be collected and peripheral blood samples for cytokines and blood bacterial DNA analysis. Both groups this same routine procedure repeated at visits 2.1, 2.2, 3, 4, 5, 6, 6.1.6.2, 6.3 and visit 7. Another safety assessment 2 weeks after FMT is to review any adverse events that may have occurred.
Both groups will have an MRI at M1, M6 and M12.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Early Intervention | Active Comparator | Fecal microbiota via enema at Month 1, 2, 3. 4, 5 and month 6 along with stool, urine and blood collection. At months 7, 8, 9, 10, 11 and 12 only stool, urine and blood collection. |
|
| Late Intervention | Active Comparator | At months 1, 2, 3, 4, 5 and 6, stool, urine and blood collection. Fecal microbiota via enema at month 6, 7, 8, 9, 10, 11and 12 months along with stool, urine and blood collection. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Fecal microbiota | Drug | fecal microbial transplantation |
|
| Measure | Description | Time Frame |
|---|---|---|
| Effect of Fecal Microbial Transplantation in Peripheral Blood Cytokines Within Relapsing Multiple Sclerosis Patients | Luminex test to evaluate the levels of 25 cytokines in peripheral blood pre-fecal transplant and post fecal transplant. Due to early termination of the trial, we didn't meet the number of participants required for statistical analysis; therefore, we analyzed the data pre and post FMT, rather than early and late intervention groups as originally planned. Due to the small sample size there was a large variation between cytokine levels of each participant for pre and post FMT, resulting in large standard deviations. | Within 6 months |
| Measure | Description | Time Frame |
|---|---|---|
| Evaluate Effect of Fecal Microbial Transplantation in Gut Microbiome | PCR (polymerase chain reaction) to assess blood DNA bacteria | Monthly for 6 months |
| Evaluate Effect of Fecal Microbial Transplantation in Gut Permeability |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Marcelo Kremenchutzky, MD, FRCP | London Health Science Centre | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| London Health Sciences Centre, University Hospital | London | Ontario | N6A 5A5 | Canada |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 25775034 | Background | Cantarel BL, Waubant E, Chehoud C, Kuczynski J, DeSantis TZ, Warrington J, Venkatesan A, Fraser CM, Mowry EM. Gut microbiota in multiple sclerosis: possible influence of immunomodulators. J Investig Med. 2015 Jun;63(5):729-34. doi: 10.1097/JIM.0000000000000192. | |
| 26367776 | Background | Miyake S, Kim S, Suda W, Oshima K, Nakamura M, Matsuoka T, Chihara N, Tomita A, Sato W, Kim SW, Morita H, Hattori M, Yamamura T. Dysbiosis in the Gut Microbiota of Patients with Multiple Sclerosis, with a Striking Depletion of Species Belonging to Clostridia XIVa and IV Clusters. PLoS One. 2015 Sep 14;10(9):e0137429. doi: 10.1371/journal.pone.0137429. eCollection 2015. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Early Intervention | Fecal microbiota via enema at Month 1, 2, 3. 4, 5 and month 6 along with stool, urine and blood collection. At months 7, 8, 9, 10, 11 and 12 only stool, urine and blood collection. Fecal microbiota: fecal microbial transplantation |
| FG001 | Late Intervention | At months 1, 2, 3, 4, 5 and 6, stool, urine and blood collection. Fecal microbiota via enema at month 6, 7, 8, 9, 10, 11and 12 months along with stool, urine and blood collection. Fecal microbiota: fecal microbial transplantation |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Early Intervention | Fecal microbiota via enema at Month 1, 2, 3. 4, 5 and month 6 along with stool, urine and blood collection. At months 7, 8, 9, 10, 11 and 12 only stool, urine and blood collection. Fecal microbiota: fecal microbial transplantation |
| BG001 | Late Intervention |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Effect of Fecal Microbial Transplantation in Peripheral Blood Cytokines Within Relapsing Multiple Sclerosis Patients | Luminex test to evaluate the levels of 25 cytokines in peripheral blood pre-fecal transplant and post fecal transplant. Due to early termination of the trial, we didn't meet the number of participants required for statistical analysis; therefore, we analyzed the data pre and post FMT, rather than early and late intervention groups as originally planned. Due to the small sample size there was a large variation between cytokine levels of each participant for pre and post FMT, resulting in large standard deviations. | Posted | Mean | Standard Deviation | ng/mL | Within 6 months |
|
1 year - Nov2017 - Nov2018
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Early Intervention | Fecal microbiota via enema at Month 1, 2, 3. 4, 5 and month 6 along with stool, urine and blood collection. At months 7, 8, 9, 10, 11 and 12 only stool, urine and blood collection. Fecal microbiota: fecal microbial transplantation |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Nausea | Gastrointestinal disorders | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Chantelle Graf, RN | Lawson Health Research Institute | 519-685-8500 | 35352 | chantelle.graf@sjhc.london.on.ca |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Oct 9, 2018 | Sep 20, 2019 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D001327 | Autoimmune Diseases |
| D009103 | Multiple Sclerosis |
| ID | Term |
|---|---|
| D007154 | Immune System Diseases |
| D020278 | Demyelinating Autoimmune Diseases, CNS |
| D020274 | Autoimmune Diseases of the Nervous System |
| D009422 | Nervous System Diseases |
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| ID | Term |
|---|---|
| D000069467 | Fecal Microbiota Transplantation |
| ID | Term |
|---|---|
| D001691 | Biological Therapy |
| D013812 | Therapeutics |
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This is a prospective, cross-over, open label, randomized 1:1 early versus delayed groups, interventional [FMT] versus no interventional [no FMT] controlled trial to explore the effects of FMT from a healthy donor to RMS patients and investigate whether this can influence disease activity based on a panel of biological markers.
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Urinalysis to evaluate lactulose and mannitol levels
| Baseline, 6 months, 12 months |
| Evaluate Treatment Clinical Safety: Neurological Exam Using the Expanded Disability Status Scale | Neurological exam using the Expanded Disability Status Scale | Monthly for 6 months |
| Evaluate Treatment Safety: MRI to Access Subclinical Disease Activity | MRI to access subclinical disease activity | Baseline, 6 months and 12 months |
| 27000242 | Background | Tremlett H, Fadrosh DW, Faruqi AA, Hart J, Roalstad S, Graves J, Lynch S, Waubant E; US Network of Pediatric MS Centers. Gut microbiota composition and relapse risk in pediatric MS: A pilot study. J Neurol Sci. 2016 Apr 15;363:153-7. doi: 10.1016/j.jns.2016.02.042. Epub 2016 Feb 20. |
| 20126401 | Background | Lavasani S, Dzhambazov B, Nouri M, Fak F, Buske S, Molin G, Thorlacius H, Alenfall J, Jeppsson B, Westrom B. A novel probiotic mixture exerts a therapeutic effect on experimental autoimmune encephalomyelitis mediated by IL-10 producing regulatory T cells. PLoS One. 2010 Feb 2;5(2):e9009. doi: 10.1371/journal.pone.0009009. |
| 22157239 | Background | Kelly CR, de Leon L, Jasutkar N. Fecal microbiota transplantation for relapsing Clostridium difficile infection in 26 patients: methodology and results. J Clin Gastroenterol. 2012 Feb;46(2):145-9. doi: 10.1097/MCG.0b013e318234570b. |
| 23416238 | Background | Kwon HK, Kim GC, Kim Y, Hwang W, Jash A, Sahoo A, Kim JE, Nam JH, Im SH. Amelioration of experimental autoimmune encephalomyelitis by probiotic mixture is mediated by a shift in T helper cell immune response. Clin Immunol. 2013 Mar;146(3):217-27. doi: 10.1016/j.clim.2013.01.001. Epub 2013 Jan 16. |
| 25843302 | Background | Mielcarz DW, Kasper LH. The gut microbiome in multiple sclerosis. Curr Treat Options Neurol. 2015 Apr;17(4):344. doi: 10.1007/s11940-015-0344-7. |
| 22674334 | Background | Hooper LV, Littman DR, Macpherson AJ. Interactions between the microbiota and the immune system. Science. 2012 Jun 8;336(6086):1268-73. doi: 10.1126/science.1223490. Epub 2012 Jun 6. |
| 27529553 | Background | Wang S, Xu M, Wang W, Cao X, Piao M, Khan S, Yan F, Cao H, Wang B. Systematic Review: Adverse Events of Fecal Microbiota Transplantation. PLoS One. 2016 Aug 16;11(8):e0161174. doi: 10.1371/journal.pone.0161174. eCollection 2016. |
At months 1, 2, 3, 4, 5 and 6, stool, urine and blood collection. Fecal microbiota via enema at month 6, 7, 8, 9, 10, 11and 12 months along with stool, urine and blood collection. Fecal microbiota: fecal microbial transplantation |
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race and Ethnicity Not Collected | Race and Ethnicity were not collected from any participant. | Count of Participants | Participants |
|
| Post-FMT |
Cytokine values after fecal microbial transplants. Fecal microbiota: fecal microbial transplantation |
|
|
| Secondary | Evaluate Effect of Fecal Microbial Transplantation in Gut Microbiome | PCR (polymerase chain reaction) to assess blood DNA bacteria | Not Posted | Monthly for 6 months | Participants |
| Secondary | Evaluate Effect of Fecal Microbial Transplantation in Gut Permeability | Urinalysis to evaluate lactulose and mannitol levels | Not Posted | Baseline, 6 months, 12 months | Participants |
| Secondary | Evaluate Treatment Clinical Safety: Neurological Exam Using the Expanded Disability Status Scale | Neurological exam using the Expanded Disability Status Scale | Not Posted | Monthly for 6 months | Participants |
| Secondary | Evaluate Treatment Safety: MRI to Access Subclinical Disease Activity | MRI to access subclinical disease activity | Not Posted | Baseline, 6 months and 12 months | Participants |
| 0 |
| 4 |
| 0 |
| 4 |
| 3 |
| 4 |
| EG001 | Late Intervention | At months 1, 2, 3, 4, 5 and 6, stool, urine and blood collection. Fecal microbiota via enema at month 6, 7, 8, 9, 10, 11and 12 months along with stool, urine and blood collection. Fecal microbiota: fecal microbial transplantation | 0 | 7 | 0 | 7 | 5 | 7 |
| Hives | Skin and subcutaneous tissue disorders | Non-systematic Assessment |
|
| Hypertension | Cardiac disorders | Non-systematic Assessment |
|
| Difficulty Swallowing | Gastrointestinal disorders | Non-systematic Assessment |
|
| Vaginal Yeast Infection | Reproductive system and breast disorders | Non-systematic Assessment |
|
| Ear Infection | Ear and labyrinth disorders | Non-systematic Assessment |
|
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| D003711 | Demyelinating Diseases |