Not provided
Not provided
Not provided
Not provided
Under-enrollment, including after interruption due to a hold on source FMT material and the COVID-19 pandemic
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
In this Phase 1b open-label prospective clinical trial, patients with relapsing-remitting MS will undergo FMT of FMP30 (donor stool) via colonoscopy and immunological efficacy endpoints will be assessed at various time points. The active phase of the study will continue for 12 weeks post-FMT with safety and biomarker (engraftment) follow-up for 48 weeks. A parallel observational control arm of MS patients who otherwise satisfy study inclusion criteria based on their MS phenotype, demographics, disease duration and prior use of allowable MS therapies, will be recruited as a comparison observational group to measure stability of stool and serum immunological measures. The study duration for the Observational Control Arm is 12 weeks.
In this Phase 1b open-label prospective clinical trial, patients with relapsing- remitting MS will undergo FMT of FMP30 (donor stool) via colonoscopy and immunological efficacy endpoints will be assessed at various time points. The active phase of the study will continue for 12 weeks post-FMT with safety and biomarker (engraftment) follow-up for 48 weeks. A parallel observational control arm of MS patients who otherwise satisfy study inclusion criteria based on their MS phenotype, demographics, disease duration and prior use of allowable MS therapies, will be recruited as a comparison observational group to measure stability of stool and serum immunological measures.
The primary hypotheses are that:
Secondary hypotheses are that:
FMP30 donor stool will be obtained from OpenBiome (Somerville, Massachusetts; OpenBiome.org), an established nonprofit stool bank with stringent safety protocols and quality control. Donor stool will be obtained from donors without Multiple Sclerosis (MS) and without other known autoimmune diseases and will be screened for transmissible pathogens. In collaboration with OpenBiome, University of California, San Francisco (UCSF) will additionally screen donor stool using in vitro assays for immunological properties thought to be favorable in Multiple Sclerosis (MS), including decreasing T helper 17 cells (TH17) and increasing T regulatory cells, in order to select the final donor stool to be used in this study for FMT. UCSF will obtain an investigational new drug (IND) from the FDA for FMT of FMP30 donor stool in MS.
After providing written informed consent and reviewing inclusion and exclusion criteria, participants will participate in either the FMT Treatment Arm or the Observational Control Arm.
Participants in the FMT Treatment Arm will first undergo screening assessments according to the study schedule of activities and provide blood samples for eligibility and research, and stool samples for research. Participants who pass screening will have their pre-treatment baseline visit with 21 days of their screening visit where they will have an MRI, safety and biomarker research blood sample collection, stool sample collection for research, complete study activities according to the study visit schedule, be given antibiotics, bowel preparation, a medication compliance diary and directions on when and how to start the antibiotics and bowel preparation before their scheduled FMT colonoscopy procedure.
The week before their Baseline FMT visit, participants will be contacted by study staff to initiate an oral antibiotic regimen for 5 days to precondition the gut for FMT and optimize engraftment of the donor microbiome. Study staff will ensure that the participants understand how to complete their oral antibiotic regimen, compliance diary, and bowel preparation correctly.
At the study Baseline Visit, following standard bowel preparation for colonoscopy, participants will then undergo colonoscopy with FMT of FMP30 by an experienced gastroenterologist. Participants will return for scheduled assessments of stool and blood sampling, questionnaires, physical examination, MS rating scales, and follow-up MRI for 12 weeks, with additional safety and biomarker blood sample collection, and followed at weeks 24, 36, and 48. The active study time of 12 weeks was designed to be short to minimize time off MS disease-modifying therapies (should the participant wish to go on a MS disease-modifying therapy).
Participants participating in the Observational Control Arm will not undergo the interventional FMT treatment. Participants in this arm will have a total of 5 visits over the course of 12 weeks. At the Screening/Baseline visit, participants will provide blood and stool samples for research along with other study activities, according to the study visit schedule. Participants will mail in a stool sample at week 2 and come in for follow-up visits at weeks 4, 8, and 12.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Interventional FMT Treatment Arm | Experimental | After providing written informed consent, participants will undergo screening and baseline assessments of stool and blood sampling, questionnaires, physical examination, MS rating scales, and MRI. Participants will then initiate an oral antibiotic regimen for 5 days to precondition the gut for the Fecal Microbiota Transplantation (FMT) of FMP30 donor stool and optimize engraftment of the FMP30 donor stool microbiome. Following standard bowel preparation for colonoscopy, participants will undergo the FMT procedure by an experienced gastroenterologist. Participants will return for scheduled assessments and follow-up MRI for 12 weeks, with additional safety and biomarker follow-up for 36 weeks. The active study time is designed to be short (12 weeks active phase) to minimize time off on other MS disease-modifying therapy (DMT). This arm of the study will last for approximately 52 weeks total (4 weeks of screening + 12 weeks active treatment phase + 36 weeks of safety follow-up). |
|
| Observational Control Arm | Active Comparator | Participants, who otherwise satisfy study inclusion criteria based on their MS phenotype, demographics, disease duration, and prior use of allowable MS therapies, will be recruited as a comparison observational group to measure stability of stool and serum immunological measures. After providing written informed consent, participants will undergo screening and baseline assessments, including collection of blood and stool samples, demographic data collection, concomitant medication review, and an MS Relapse assessment. At week 2, participants will mail in stool samples with a prepaid air bill and packaging. Weeks 4, 8, and 12 assessments will include concomitant medication review, relapse assessment, and blood and stool collection. The duration of the study for the observational control arm will last for 12 weeks. All study procedures will be performed at the University of California, San Francisco. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| FMP30 Donor Stool | Drug | FMP30 is manufactured by the non-profit stool bank Openbiome. Each FMP30 filtered donor stool engraftment has approximately 12.5g of stool per 30mL of normal saline. It is homogenized in sterile normal saline. |
| Measure | Description | Time Frame |
|---|---|---|
| Participants Who Complete the Study Protocol | This includes the proportion of participants who completed the study protocol, including the completion of the study visits at baseline, 2 weeks, 4 weeks, 8 weeks, 12 weeks, and a safety follow-up through week 48. | Baseline through week 48 |
| Change in Fecal Microbiota | Engraftment: Change in fecal microbiota community structure at Baseline Visit, 2 weeks, 4 weeks, 8 weeks, 12 weeks by 16S ribosomal RNA amplicon sequencing (as a measure of the diversity of fecal microbiota by detecting sequence variations). Comment on unit of measure: The Shannon Index is used to assess changes in fecal microbiota diversity, with higher values indicating greater microbial diversity. Changes in the Shannon index over time will reflect the impact of the intervention on gut microbial composition. | Baseline Visit, 2 weeks, 4 weeks, 8 weeks, and 12 weeks. |
| Number of Treatment-Emergent Serious Adverse Events [Safety and Tolerability] | Treatment-emergent serious adverse events from baseline through week 12. The proportion of participants who develop an adverse event (AE) of severity grade 2 or more by NIH CTCAE criteria V4.0 is considered serious. NIH CTCAE is a standardized classification and severity grading scale for adverse events used in clinical trials. The CTCAE displays Grades 1 through 5 with unique clinical descriptions of severity for each AE. Grade 1 is considered mild, Grade 2 as moderate, Grade 3 as severe or medically significant, Grade 4 as life-threatening, and Grade 5 as death related to AE. | Baseline Visit, 2 weeks, 4 weeks, 8 weeks, and 12 weeks. |
| Number of Treatment-Emergent Non-Serious Adverse Events [Safety and Tolerability] | Treatment-emergent non-serious adverse events from baseline through week 12. The proportion of participants who develop an adverse event (AE) of severity grade 2 or more by NIH CTCAE criteria V4.0 is considered serious. NIH CTCAE is a standardized classification and severity grading scale for adverse events used in clinical trials. The CTCAE displays Grades 1 through 5 with unique clinical descriptions of severity for each AE. Grade 1 is considered mild, Grade 2 as moderate, Grade 3 as severe or medically significant, Grade 4 as life-threatening, and Grade 5 as death related to AE. |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Plasma CD19+ B Cells in Interventional Arm [CD19: Cluster of Differentiation Antigen 19] | Plasma CD19+ B cell count will be measured as absolute cell counts (cells/uL) at Baseline Visit, 2 weeks, 4 weeks, 8 weeks, and 12 weeks. | Baseline Visit, 2 weeks, 4 weeks, 8 weeks, and 12 weeks. |
| Change in Plasma CD19+ B Cells in Observational Arm |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Jeffrey Gelfand, MD, MAS | UCSF Multiple Sclerosis Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| UCSF Multiple Sclerosis Center | San Francisco | California | 94158 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 28893978 | Background | Cekanaviciute E, Yoo BB, Runia TF, Debelius JW, Singh S, Nelson CA, Kanner R, Bencosme Y, Lee YK, Hauser SL, Crabtree-Hartman E, Sand IK, Gacias M, Zhu Y, Casaccia P, Cree BAC, Knight R, Mazmanian SK, Baranzini SE. Gut bacteria from multiple sclerosis patients modulate human T cells and exacerbate symptoms in mouse models. Proc Natl Acad Sci U S A. 2017 Oct 3;114(40):10713-10718. doi: 10.1073/pnas.1711235114. Epub 2017 Sep 11. | |
| 28531908 |
Not provided
Not provided
Outcome data as well as study data related to diagnosis, disease presentation, and date of birth, along with biological specimens collected as part of the study, may be shared (in coded form) in the future with other qualified researchers on a case by case basis at the discretion of the PI and Co-PIs. Any such investigator will be required to provide appropriate documentation that the research being conducted has been approved by an Institutional Review Board and demonstrate that it will be of value in determining the cause of MS or a related disorder, and as allowed by the UCSF Institutional Review Board.
After initial study results are published and on a case by case basis.
Limited data to include demographic and clinical information and biological specimens collected as part of the study, may be shared (in coded form) in the future with other qualified researchers on a case by case basis at the discretion of the PI and Co-PIs. Any such investigator will be required to provide appropriate documentation that the research being conducted has been approved by an Institutional Review Board and demonstrate that it will be of value in determining the cause of MS or a related disorder, and as allowed by the UCSF Institutional Review Board.
Not provided
Screening period
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Interventional FMT Treatment Arm | After providing written informed consent, subjects underwent screening and baseline assessments of stool and blood sampling, questionnaires, physical examination, MS rating scales, and MRI. Subjects then initiated an oral antibiotic regimen for 5 days to precondition the gut for the Fecal Microbiota Transplantation (FMT) of FMP30 donor stool and try to optimize engraftment of the FMP30 donor stool microbiome. Following standard bowel preparation for colonoscopy, subjects underwent the FMT procedure by an experienced gastroenterologist. Subjects returned for scheduled assessments and follow-up MRI for 12 weeks, with additional safety and biomarker follow-up for 36 weeks. FMP30 Donor Stool: FMP30 was manufactured by the non-profit stool bank Openbiome. Each FMP30 filtered donor stool engraftment has approximately 12.5g of stool per 30mL of normal saline. It is homogenized in sterile normal saline. Fecal Microbiota Transplantation (FMT) of FMP30 Donor Stool: Three doses of filtered donor stool engraftments homogenized in sterile normal saline (FMP30) obtained from the non-profit stool bank OpenBiome were administered via colonoscopy. |
| FG001 | Observational Control Arm | Subjects, who otherwise satisfy study inclusion criteria based on their MS phenotype, demographics, disease duration and prior use of allowable MS therapies, will be recruited as a comparison observational group to measure stability of stool and serum immunological measures. After providing written informed consent, subjects will undergo screening and baseline assessments, including collection of blood and stool samples, demographic data collection, concomitant medication review, and an MS Relapse assessment. At week 2, subjects will mail in stool samples with a prepaid air bill and packaging. Weeks 4, 8, and 12 assessments will include concomitant medication review, relapse assessment, and blood and stool collection. The duration of the study for the observational control arm will last for 12 weeks. All study procedures will be performed at the University of California, San Francisco. Observational Control: Subjects, who otherwise satisfy study inclusion criteria based on their MS phenotype, demographics, disease duration and prior use of allowable MS therapies, will be recruited as a comparison observational group to measure stability of stool and serum immunological measures. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
4 participants were recruited for the interventional arm and 1 for the observational control arm.
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Interventional FMT Treatment Arm | After providing written informed consent, participants underwent screening and baseline assessments of stool and blood sampling, questionnaires, physical examination, MS rating scales, and MRI. Participants then initiated an oral antibiotic regimen for 5 days to precondition the gut for the Fecal Microbiota Transplantation (FMT) of FMP30 donor stool and try to optimize engraftment of the FMP30 donor stool microbiome. Following standard bowel preparation for colonoscopy, participants underwent the FMT procedure by an experienced gastroenterologist. Participants returned for scheduled assessments and follow-up MRI for 12 weeks, with additional safety and biomarker follow-up for 36 weeks. FMP30 Donor Stool: FMP30 was manufactured by the non-profit stool bank Openbiome. Each FMP30 filtered donor stool engraftment has approximately 12.5g of stool per 30mL of normal saline. It is homogenized in sterile normal saline. Fecal Microbiota Transplantation (FMT) of FMP30 Donor Stool: Three doses of filtered donor stool engraftments homogenized in sterile normal saline (FMP30) obtained from the non-profit stool bank OpenBiome were administered via colonoscopy. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| 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 | Participants Who Complete the Study Protocol | This includes the proportion of participants who completed the study protocol, including the completion of the study visits at baseline, 2 weeks, 4 weeks, 8 weeks, 12 weeks, and a safety follow-up through week 48. | All enrolled participants who received FMT completed the study protocol; however, the study was interrupted due to the COVID-19 pandemic and a hold on the source material, and was subsequently closed to further enrollment. | Posted | Count of Participants | Participants | Baseline through week 48 |
|
12-week treatment phase (FMT) and 36-week safety follow-up for the interventional arm, and 12 weeks for the observational arm.
The proportion of participants who develop an adverse event (AE) of severity grade 2 or more by NIH CTCAE criteria V4.0 is considered serious. NIH CTCAE is a standardized classification and severity grading scale used for AEs in clinical trials. The CTCAE displays Grades 1 through 5 with unique clinical descriptions of severity for each AE. Grade 1 is considered mild, Grade 2 as moderate, Grade 3 as severe or medically significant, Grade 4 as life-threatening, and Grade 5 as death related to AE.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Number of Events at 12 Weeks for Interventional FMT Treatment Arm | After providing written informed consent, participants underwent screening and baseline assessments of stool and blood sampling, questionnaires, physical examination, MS rating scales, and MRI. Participants then initiated an oral antibiotic regimen for 5 days to precondition the gut for the Fecal Microbiota Transplantation (FMT) of FMP30 donor stool and try to optimize engraftment of the FMP30 donor stool microbiome. Following standard bowel preparation for colonoscopy, participants underwent the FMT procedure by an experienced gastroenterologist. Participants returned for scheduled assessments and follow-up MRI for 12 weeks, with additional safety and biomarker follow-up for 36 weeks. FMP30 Donor Stool: FMP30 was manufactured by the non-profit stool bank Openbiome. Each FMP30 filtered donor stool engraftment has approximately 12.5g of stool per 30mL of normal saline. It is homogenized in sterile normal saline. Fecal Microbiota Transplantation (FMT) of FMP30 Donor Stool: Three doses of filtered donor stool engraftments homogenized in sterile normal saline (FMP30) obtained from the non-profit stool bank OpenBiome were administered via colonoscopy. |
Not provided
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Conjunctivitis | Eye disorders | Non-systematic Assessment |
The study was not fully recruited. Study recruitment was interrupted by both the COVID-19 pandemic and a hold on the FMT source material. Participants recruited up until that point were analyzed with available safety and outcome data reported.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Jeffrey Gelfand, MD, MAS | University of California, San Francisco | 415-353-2069 | Jeffrey.Gelfand@ucsf.edu |
Not provided
| 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 | Mar 29, 2021 | Jan 10, 2025 | Prot_SAP_000.pdf |
Not provided
| ID | Term |
|---|---|
| D020529 | Multiple Sclerosis, Relapsing-Remitting |
| D009103 | Multiple Sclerosis |
| ID | Term |
|---|---|
| D020278 | Demyelinating Autoimmune Diseases, CNS |
| D020274 | Autoimmune Diseases of the Nervous System |
| D009422 | Nervous System Diseases |
| D003711 | Demyelinating Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| D000069467 | Fecal Microbiota Transplantation |
| ID | Term |
|---|---|
| D001691 | Biological Therapy |
| D013812 | Therapeutics |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Fecal Microbiota Transplantation (FMT) of FMP30 Donor Stool | Procedure | Three doses of filtered donor stool engraftments homogenized in sterile normal saline (FMP30), obtained from the non-profit stool bank OpenBiome, will be administered via colonoscopy in patients with Relapsing-Remitting Multiple Sclerosis. FMT dosage via colonoscopy may include a lower amount of transplanted stool at the discretion of the study gastroenterologist if there are any peri-procedural safety or technical considerations. Total FMT dose (in milliliters) will be documented. |
|
| Observational Control | Other | Participants, who otherwise satisfy study inclusion criteria based on their MS phenotype, demographics, disease duration, and prior use of allowable MS therapies will be recruited as a comparison observational group to measure stability of stool and serum immunological measures. |
|
| Baseline Visit, 2 weeks, 4 weeks, 8 weeks, and 12 weeks. |
Plasma CD19+ B cell count will be measured as absolute cell counts (cells/uL) at Baseline Visit, 2 weeks, 4 weeks, 8 weeks, and 12 weeks. |
| Baseline Visit, 2 weeks, 4 weeks, 8 weeks, and 12 weeks. |
| Change in Serum IgA Immunoglobulin Levels in Interventional Arm [IgA: Immunoglobulin A] | Serum Immunoglobulin levels of IgA will be measured in mg/dL at Baseline Visit, 2 weeks, 4 weeks, 8 weeks, and 12 weeks. | Baseline Visit, 2 weeks, 4 weeks, 8 weeks, and 12 weeks. |
| Change in Serum IgA Immunoglobulin Levels in Observational Arm | Serum Immunoglobulin levels of IgA will be measured in mg/dL at Baseline Visit, 2 weeks, 4 weeks, and 12 weeks. | Baseline Visit, 2 weeks, 4 weeks, and 12 weeks. |
| Change in Serum IgM Immunoglobulin Levels in Interventional Arm [IgM: Immunoglobulin M] | Serum Immunoglobulin levels of IgM will be measured in mg/dL at Baseline Visit, 2 weeks, 4 weeks, 8 weeks, and 12 weeks. | Baseline Visit, 2 weeks, 4 weeks, 8 weeks and 12 weeks. |
| Change in Serum IgM Immunoglobulin Levels in Observational Arm | Serum Immunoglobulin levels of IgM will be measured in mg/dL at Baseline Visit, 2 weeks, 4 weeks, 8 weeks, and 12 weeks. The percentage of change from baseline for each time point is also reported. | Baseline Visit, 2 weeks, 4 weeks, 8 weeks and 12 weeks. |
| Change in Serum IgG Immunoglobulin Levels in Interventional Arm [IgG: Immunoglobulin G] | Serum Immunoglobulin levels of IgG will be measured in mg/dL at Baseline Visit, 2 weeks, 4 weeks, 8 weeks, and 12 weeks. | Baseline Visit, 2 weeks, 4 weeks, 8 weeks and 12 weeks |
| Change in Serum IgG Immunoglobulin Levels in Observational Arm | Serum Immunoglobulin levels of IgG will be measured in mg/dL at Baseline Visit, 2 weeks, 4 weeks, 8 weeks, and 12 weeks. | Baseline Visit, 2 weeks, 4 weeks, 8 weeks and 12 weeks |
| Incidence of New T2/FLAIR Lesions | The number of new or enlarging T2/FLAIR lesions will be counted at pre-treatment and week 12. | At pre-treatment visit and week 12. |
| Treatment-emergent Gadolinium Enhancing Lesions | New treatment-emergent gadolinium-enhancing lesions on brain MRI. | At pre-treatment visit and week 12. |
| Clinical Relapse | Clinical relapse through week 12 (treatment phase) | From baseline to week 12 |
| Percentage of Induced T-regulatory Cells | Flow cytometric analysis of peripheral blood mononuclear cells (PBMC) from each participant and at each time point. T-regs were induced by stimulation of PBMCs with anti-CD3 and anti-CD28 antibodies in the presence of IL2 and TGFb. The percentage of T-regs before and after FMT was analyzed. FMT was performed during the baseline visit. [CD3: cluster of differentiation 3, CD28: cluster of differentiation 28, IL2: interleukin2, TGFb: Transforming growth factor beta] | Pre-screening, Screening, Baseline, Week 2, Week 4, Week 8, Week 12, Week 24, Week 36, Week 48 |
| Background |
| Bafeta A, Yavchitz A, Riveros C, Batista R, Ravaud P. Methods and Reporting Studies Assessing Fecal Microbiota Transplantation: A Systematic Review. Ann Intern Med. 2017 Jul 4;167(1):34-39. doi: 10.7326/M16-2810. Epub 2017 May 23. |
| 25607761 | Background | Morris MS, Graham LA, Chu DI, Cannon JA, Hawn MT. Oral Antibiotic Bowel Preparation Significantly Reduces Surgical Site Infection Rates and Readmission Rates in Elective Colorectal Surgery. Ann Surg. 2015 Jun;261(6):1034-40. doi: 10.1097/SLA.0000000000001125. |
| 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. |
| 28462225 | Background | Ochoa-Reparaz J, Magori K, Kasper LH. The chicken or the egg dilemma: intestinal dysbiosis in multiple sclerosis. Ann Transl Med. 2017 Mar;5(6):145. doi: 10.21037/atm.2017.01.18. |
| 24018052 | Background | Smits LP, Bouter KE, de Vos WM, Borody TJ, Nieuwdorp M. Therapeutic potential of fecal microbiota transplantation. Gastroenterology. 2013 Nov;145(5):946-53. doi: 10.1053/j.gastro.2013.08.058. Epub 2013 Sep 7. |
| 27352007 | Background | Jangi S, Gandhi R, Cox LM, Li N, von Glehn F, Yan R, Patel B, Mazzola MA, Liu S, Glanz BL, Cook S, Tankou S, Stuart F, Melo K, Nejad P, Smith K, Topcuolu BD, Holden J, Kivisakk P, Chitnis T, De Jager PL, Quintana FJ, Gerber GK, Bry L, Weiner HL. Alterations of the human gut microbiome in multiple sclerosis. Nat Commun. 2016 Jun 28;7:12015. doi: 10.1038/ncomms12015. |
| 26757463 | Background | Lee CH, Steiner T, Petrof EO, Smieja M, Roscoe D, Nematallah A, Weese JS, Collins S, Moayyedi P, Crowther M, Ropeleski MJ, Jayaratne P, Higgins D, Li Y, Rau NV, Kim PT. Frozen vs Fresh Fecal Microbiota Transplantation and Clinical Resolution of Diarrhea in Patients With Recurrent Clostridium difficile Infection: A Randomized Clinical Trial. JAMA. 2016 Jan 12;315(2):142-9. doi: 10.1001/jama.2015.18098. |
| 28422836 | Background | Uygun A, Ozturk K, Demirci H, Oger C, Avci IY, Turker T, Gulsen M. Fecal microbiota transplantation is a rescue treatment modality for refractory ulcerative colitis. Medicine (Baltimore). 2017 Apr;96(16):e6479. doi: 10.1097/MD.0000000000006479. |
| 28586116 | Background | Bajaj JS, Kassam Z, Fagan A, Gavis EA, Liu E, Cox IJ, Kheradman R, Heuman D, Wang J, Gurry T, Williams R, Sikaroodi M, Fuchs M, Alm E, John B, Thacker LR, Riva A, Smith M, Taylor-Robinson SD, Gillevet PM. Fecal microbiota transplant from a rational stool donor improves hepatic encephalopathy: A randomized clinical trial. Hepatology. 2017 Dec;66(6):1727-1738. doi: 10.1002/hep.29306. Epub 2017 Oct 30. |
| BG001 | Observational Control Arm | Participants, who otherwise satisfy study inclusion criteria based on their MS phenotype, demographics, disease duration and prior use of allowable MS therapies, will be recruited as a comparison observational group to measure stability of stool and serum immunological measures. After providing written informed consent, participants will undergo screening and baseline assessments, including collection of blood and stool samples, demographic data collection, concomitant medication review, and an MS Relapse assessment. At week 2, participants will mail in stool samples with a prepaid air bill and packaging. Weeks 4, 8, and 12 assessments will include concomitant medication review, relapse assessment, and blood and stool collection. The duration of the study for the observational control arm will last for 12 weeks. All study procedures will be performed at the University of California, San Francisco. Observational Control: Participants, who otherwise satisfy study inclusion criteria based on their MS phenotype, demographics, disease duration, and prior use of allowable MS therapies, will be recruited as a comparison observational group to measure stability of stool and serum immunological measures. |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| OG001 | Observational Control Arm | Participants, who otherwise satisfy study inclusion criteria based on their MS phenotype, demographics, disease duration and prior use of allowable MS therapies, will be recruited as a comparison observational group to measure stability of stool and serum immunological measures. After providing written informed consent, participants will undergo screening and baseline assessments, including collection of blood and stool samples, demographic data collection, concomitant medication review, and an MS Relapse assessment. At week 2, participants will mail in stool samples with a prepaid air bill and packaging. Weeks 4, 8, and 12 assessments will include concomitant medication review, relapse assessment, and blood and stool collection. The duration of the study for the observational control arm will last for 12 weeks. All study procedures will be performed at the University of California, San Francisco. Observational Control: Participants, who otherwise satisfy study inclusion criteria based on their MS phenotype, demographics, disease duration and prior use of allowable MS therapies, will be recruited as a comparison observational group to measure stability of stool and serum immunological measures. |
|
|
| Primary | Change in Fecal Microbiota | Engraftment: Change in fecal microbiota community structure at Baseline Visit, 2 weeks, 4 weeks, 8 weeks, 12 weeks by 16S ribosomal RNA amplicon sequencing (as a measure of the diversity of fecal microbiota by detecting sequence variations). Comment on unit of measure: The Shannon Index is used to assess changes in fecal microbiota diversity, with higher values indicating greater microbial diversity. Changes in the Shannon index over time will reflect the impact of the intervention on gut microbial composition. | No samples were collected for the control participant at any of the time points ( Baseline, 2 weeks, 4 weeks, 8 weeks, 12 weeks) as the study was interrupted due to COVID-19. We don't have data to report for the change in microbiota structure for the control participant, who did not receive an intervention. This data will also not be reported in the future (as it was not collected). | Posted | Number | Shannon index | Baseline Visit, 2 weeks, 4 weeks, 8 weeks, and 12 weeks. |
|
|
|
| Primary | Number of Treatment-Emergent Serious Adverse Events [Safety and Tolerability] | Treatment-emergent serious adverse events from baseline through week 12. The proportion of participants who develop an adverse event (AE) of severity grade 2 or more by NIH CTCAE criteria V4.0 is considered serious. NIH CTCAE is a standardized classification and severity grading scale for adverse events used in clinical trials. The CTCAE displays Grades 1 through 5 with unique clinical descriptions of severity for each AE. Grade 1 is considered mild, Grade 2 as moderate, Grade 3 as severe or medically significant, Grade 4 as life-threatening, and Grade 5 as death related to AE. | All participants were monitored for the number of treatment-emergent serious adverse events from baseline through week 12. | Posted | Number | number of events | Baseline Visit, 2 weeks, 4 weeks, 8 weeks, and 12 weeks. |
|
|
|
| Primary | Number of Treatment-Emergent Non-Serious Adverse Events [Safety and Tolerability] | Treatment-emergent non-serious adverse events from baseline through week 12. The proportion of participants who develop an adverse event (AE) of severity grade 2 or more by NIH CTCAE criteria V4.0 is considered serious. NIH CTCAE is a standardized classification and severity grading scale for adverse events used in clinical trials. The CTCAE displays Grades 1 through 5 with unique clinical descriptions of severity for each AE. Grade 1 is considered mild, Grade 2 as moderate, Grade 3 as severe or medically significant, Grade 4 as life-threatening, and Grade 5 as death related to AE. | All participants were monitored for the number of treatment-emergent non-serious adverse events from baseline through week 12. | Posted | Number | Number of events | Baseline Visit, 2 weeks, 4 weeks, 8 weeks, and 12 weeks. |
|
|
|
| Secondary | Change in Plasma CD19+ B Cells in Interventional Arm [CD19: Cluster of Differentiation Antigen 19] | Plasma CD19+ B cell count will be measured as absolute cell counts (cells/uL) at Baseline Visit, 2 weeks, 4 weeks, 8 weeks, and 12 weeks. | Plasma CD19+ cell counts were measured at Weeks 0, 2, 4, 8, and 12. Some participants were not able to complete the visit due to the COVID-19 pandemic; therefore, the number of participants analyzed is 0. | Posted | Number | cells/uL | Baseline Visit, 2 weeks, 4 weeks, 8 weeks, and 12 weeks. |
|
|
|
| Secondary | Change in Plasma CD19+ B Cells in Observational Arm | Plasma CD19+ B cell count will be measured as absolute cell counts (cells/uL) at Baseline Visit, 2 weeks, 4 weeks, 8 weeks, and 12 weeks. | Plasma CD19+ cell counts were measured at Weeks 0, 2, 4, 8, and 12. Some participants were not able to complete the visit due to the COVID-19 pandemic; therefore, the number of participants analyzed is 0. | Posted | Number | cells/uL | Baseline Visit, 2 weeks, 4 weeks, 8 weeks, and 12 weeks. |
|
|
|
| Secondary | Change in Serum IgA Immunoglobulin Levels in Interventional Arm [IgA: Immunoglobulin A] | Serum Immunoglobulin levels of IgA will be measured in mg/dL at Baseline Visit, 2 weeks, 4 weeks, 8 weeks, and 12 weeks. | Serum immunoglobulin levels at Weeks 0, 2, 4, 8, and 12 were collected. Some participants were not able to complete the visit due to the COVID-19 pandemic; therefore, the number of participants analyzed is 0. | Posted | Number | mg/dL | Baseline Visit, 2 weeks, 4 weeks, 8 weeks, and 12 weeks. |
|
|
|
| Secondary | Change in Serum IgA Immunoglobulin Levels in Observational Arm | Serum Immunoglobulin levels of IgA will be measured in mg/dL at Baseline Visit, 2 weeks, 4 weeks, and 12 weeks. | Serum immunoglobulin levels at Weeks 0, 2, 4, 8, and 12 were collected. Some participants were not able to complete the visit due to the COVID-19 pandemic; therefore, the number of participants analyzed is 0. | Posted | Number | mg/dL | Baseline Visit, 2 weeks, 4 weeks, and 12 weeks. |
|
|
|
| Secondary | Change in Serum IgM Immunoglobulin Levels in Interventional Arm [IgM: Immunoglobulin M] | Serum Immunoglobulin levels of IgM will be measured in mg/dL at Baseline Visit, 2 weeks, 4 weeks, 8 weeks, and 12 weeks. | Serum immunoglobulin levels at Weeks 0, 2, 4, 8, and 12 were collected. Some participants were not able to complete the visit due to the COVID-19 pandemic; therefore, the number of participants analyzed is 0. | Posted | Number | mg/dL | Baseline Visit, 2 weeks, 4 weeks, 8 weeks and 12 weeks. |
|
|
|
| Secondary | Change in Serum IgM Immunoglobulin Levels in Observational Arm | Serum Immunoglobulin levels of IgM will be measured in mg/dL at Baseline Visit, 2 weeks, 4 weeks, 8 weeks, and 12 weeks. The percentage of change from baseline for each time point is also reported. | Serum immunoglobulin levels at Weeks 0, 2, 4, 8, and 12 were collected. Some participants were not able to complete the visit due to the COVID-19 pandemic; therefore, the number of participants analyzed is 0. | Posted | Number | mg/dL | Baseline Visit, 2 weeks, 4 weeks, 8 weeks and 12 weeks. |
|
|
|
| Secondary | Change in Serum IgG Immunoglobulin Levels in Interventional Arm [IgG: Immunoglobulin G] | Serum Immunoglobulin levels of IgG will be measured in mg/dL at Baseline Visit, 2 weeks, 4 weeks, 8 weeks, and 12 weeks. | Serum immunoglobulin levels at Weeks 0, 2, 4, 8, and 12 were collected. Some participants were not able to complete the visit due to the COVID-19 pandemic; therefore, the number of participants analyzed is 0. | Posted | Number | mg/dL | Baseline Visit, 2 weeks, 4 weeks, 8 weeks and 12 weeks |
|
|
|
| Secondary | Change in Serum IgG Immunoglobulin Levels in Observational Arm | Serum Immunoglobulin levels of IgG will be measured in mg/dL at Baseline Visit, 2 weeks, 4 weeks, 8 weeks, and 12 weeks. | Serum immunoglobulin levels at Weeks 0, 2, 4, 8, and 12 were collected. Some participants were not able to complete the visit due to the COVID-19 pandemic; therefore, the number of participants analyzed is 0. | Posted | Number | mg/dL | Baseline Visit, 2 weeks, 4 weeks, 8 weeks and 12 weeks |
|
|
|
| Secondary | Incidence of New T2/FLAIR Lesions | The number of new or enlarging T2/FLAIR lesions will be counted at pre-treatment and week 12. | After screening, participants undergo MRI at pre-treatment and at Week 12 to assess for any new T2/FLAIR lesions during the treatment period in both the interventional and observational arms. | Posted | Number | number of lesions | At pre-treatment visit and week 12. |
|
|
|
| Secondary | Treatment-emergent Gadolinium Enhancing Lesions | New treatment-emergent gadolinium-enhancing lesions on brain MRI. | After screening, participants undergo MRI at pre-treatment and at Week 12 to assess for any new enhancing lesions in both the interventional and observational arms. | Posted | Number | number of enhancing lesions | At pre-treatment visit and week 12. |
|
|
|
| Secondary | Clinical Relapse | Clinical relapse through week 12 (treatment phase) | Participants were monitored for clinical relapse through week 12. | Posted | Number | Number of clinical relapses | From baseline to week 12 |
|
|
|
| Secondary | Percentage of Induced T-regulatory Cells | Flow cytometric analysis of peripheral blood mononuclear cells (PBMC) from each participant and at each time point. T-regs were induced by stimulation of PBMCs with anti-CD3 and anti-CD28 antibodies in the presence of IL2 and TGFb. The percentage of T-regs before and after FMT was analyzed. FMT was performed during the baseline visit. [CD3: cluster of differentiation 3, CD28: cluster of differentiation 28, IL2: interleukin2, TGFb: Transforming growth factor beta] | Participants who completed the treatment arm were assessed for changes in fecal microbiota using 16S ribosomal RNA sequencing. Per the study protocol, no FMT intervention was performed in participants from the observation arm; therefore, only participants in the interventional arm are included in this secondary outcome analysis. Some participants were not able to complete the visit due to the COVID-19 pandemic; therefore, the number of participants analyzed is 0. | Posted | Number | percentage of T-regs | Pre-screening, Screening, Baseline, Week 2, Week 4, Week 8, Week 12, Week 24, Week 36, Week 48 |
|
|
|
| 0 |
| 4 |
| 0 |
| 4 |
| 4 |
| 4 |
| EG001 | Number of Events at 36 Weeks for Interventional FMT Treatment Arm | After providing written informed consent, participants underwent screening and baseline assessments of stool and blood sampling, questionnaires, physical examination, MS rating scales, and MRI. Participants then initiated an oral antibiotic regimen for 5 days to precondition the gut for the Fecal Microbiota Transplantation (FMT) of FMP30 donor stool and try to optimize engraftment of the FMP30 donor stool microbiome. Following standard bowel preparation for colonoscopy, participants underwent the FMT procedure by an experienced gastroenterologist. Participants returned for scheduled assessments and follow-up MRI for 12 weeks, with additional safety and biomarker follow-up for 36 weeks. FMP30 Donor Stool: FMP30 was manufactured by the non-profit stool bank Openbiome. Each FMP30 filtered donor stool engraftment has approximately 12.5g of stool per 30mL of normal saline. It is homogenized in sterile normal saline. Fecal Microbiota Transplantation (FMT) of FMP30 Donor Stool: Three doses of filtered donor stool engraftments homogenized in sterile normal saline (FMP30) obtained from the non-profit stool bank OpenBiome were administered via colonoscopy. | 0 | 4 | 0 | 4 | 4 | 4 |
| EG002 | Number of Events at 12 Weeks for Observational Control Arm | Participants, who otherwise satisfy study inclusion criteria based on their MS phenotype, demographics, disease duration, and prior use of allowable MS therapies, will be recruited as a comparison observational group to measure stability of stool and serum immunological measures. After providing written informed consent, participants will undergo screening and baseline assessments, including collection of blood and stool samples, demographic data collection, concomitant medication review, and an MS Relapse assessment. At week 2, participants will mail in stool samples with a prepaid air bill and packaging. Weeks 4, 8, and 12 assessments will include concomitant medication review, relapse assessment, and blood and stool collection. The duration of the study for the observational control arm will last for 12 weeks. All study procedures will be performed at the University of California, San Francisco. | 0 | 1 | 0 | 1 | 0 | 1 |
| Abdominal cramping / stomach upset | Gastrointestinal disorders | Non-systematic Assessment |
|
| Constipation | Gastrointestinal disorders | Non-systematic Assessment | Mild, transient |
|
| Diarrhea/Loose Stool | Gastrointestinal disorders | Non-systematic Assessment |
|
| Dysgeusia | Gastrointestinal disorders | Non-systematic Assessment |
|
| Heartburn | Gastrointestinal disorders | Non-systematic Assessment |
|
| Nausea | Gastrointestinal disorders | Non-systematic Assessment |
|
| Drowsiness | General disorders | Non-systematic Assessment |
|
| Injection reaction to MS medication | General disorders | Non-systematic Assessment |
|
| Neutropenia | General disorders | Non-systematic Assessment | Grade 1, transient |
|
| Temperature regulation (felt warmer or colder) | General disorders | Non-systematic Assessment |
|
| Intertrigo | Infections and infestations | Non-systematic Assessment |
|
| Otitis Media | Infections and infestations | Non-systematic Assessment |
|
| Upper Respiratory Infection | Infections and infestations | Non-systematic Assessment |
|
| Urinary Tract Infection | Infections and infestations | Non-systematic Assessment |
|
| Fall | Injury, poisoning and procedural complications | Non-systematic Assessment |
|
| Spider bite | Injury, poisoning and procedural complications | Non-systematic Assessment |
|
| AST elevation (<2.5x normal) | Investigations | Non-systematic Assessment |
|
| Leukopenia | Investigations | Non-systematic Assessment | Mild, transient |
|
| Lumbar Strain | Musculoskeletal and connective tissue disorders | Non-systematic Assessment |
|
| Dizziness | Nervous system disorders | Non-systematic Assessment |
|
| Headache | Nervous system disorders | Non-systematic Assessment |
|
| Heat related worsening of neurologic symptoms (typical of MS) | Nervous system disorders | Non-systematic Assessment |
|
| Numbness / Tingling (transient) | Nervous system disorders | Non-systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
|
| Scalp itch | Skin and subcutaneous tissue disorders | Non-systematic Assessment |
|
| Deep Vein Thrombosis | Vascular disorders | Non-systematic Assessment |
|
Not provided
Not provided
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |
|
| Participant 2 |
|
|
| Participant 3 |
|
|
| Participant 4 |
|
|
|
| Observational arm |
|
|
|
| Observational arm |
|
|
|
| Participant 2 |
|
|
| Participant 3 |
|
|
| Participant 4 |
|
|
|
| Participant 2 |
|
|
| Participant 3 |
|
|
| Participant 4 |
|
|
|
| Participant 2 |
|
|
| Participant 3 |
|
|
| Participant 4 |
|
|
|
| Participant 2 |
|
|
| Participant 3 |
|
|
| Participant 4 |
|
|
| Observational arm |
|
|
| Observational arm |
|
|
|
| Participant 2 |
|
|
| Participant 3 |
|
|
| Participant 4 |
|
|