Fecal Microbiota Transplantation (FMT) of FMP30 in Relapsing-Remitting
Fecal Microbiota Transplantation (FMT) of FMP30 in Relapsing-Remitting Multiple Sclerosis: A Phase 1b Clinical Trial to Evaluate Feasibility, Safety, Tolerability and Effects on Immune Function
What it found
The trial ended early for another reason (see below).
Reason given: Under-enrollment, including after interruption due to a hold on source FMT material and the COVID-19 pandemic
What was tested
Treatment tested
- FMP30 Donor Stool
- Fecal Microbiota Transplantation (FMT) of FMP30 Donor Stool
Compared with
- Observational Control
Results by group
Participants Who Complete the Study Protocol
Baseline through week 48
| Group | Value | Interval | Number analysed |
|---|---|---|---|
| Interventional FMT Treatment Arm | 4 Participants | 4 | |
| Observational Control Arm | 1 Participants | 1 |
Interventional FMT Treatment Arm
Observational Control Arm
Change in Fecal Microbiota
Baseline Visit, 2 weeks, 4 weeks, 8 weeks, and 12 weeks.
| Group | Value | Interval | Number analysed |
|---|---|---|---|
| Change in Microbiota Structure at Baseline in FMT Treatment Arm | 0.87 Shannon index | 4 | |
| Change in Microbiota Structure at Week 2 in FMT Treatment Arm | 4.60 Shannon index | 4 | |
| Change in Microbiota Structure at Week 4 in FMT Treatment Arm | 4.10 Shannon index | 4 | |
| Change in Microbiota Structure at Week 8 in FMT Treatment Arm | 4.50 Shannon index | 4 | |
| Change in Microbiota Structure at Week 12 in FMT Treatment Arm | 4.10 Shannon index | 4 | |
| Change in Microbiota Structure at Baseline in FMT Treatment Arm | 1.10 Shannon index | 4 | |
| Change in Microbiota Structure at Week 2 in FMT Treatment Arm | 5.78 Shannon index | 4 | |
| Change in Microbiota Structure at Week 4 in FMT Treatment Arm | 5.70 Shannon index | 4 | |
| Change in Microbiota Structure at Week 8 in FMT Treatment Arm | 5.80 Shannon index | 4 | |
| Change in Microbiota Structure at Week 12 in FMT Treatment Arm | 5.85 Shannon index | 4 | |
| Change in Microbiota Structure at Baseline in FMT Treatment Arm | 5.10 Shannon index | 4 | |
| Change in Microbiota Structure at Week 2 in FMT Treatment Arm | 5.60 Shannon index | 4 | |
| Change in Microbiota Structure at Week 4 in FMT Treatment Arm | 5.15 Shannon index | 4 | |
| Change in Microbiota Structure at Week 8 in FMT Treatment Arm | 5.18 Shannon index | 4 | |
| Change in Microbiota Structure at Week 12 in FMT Treatment Arm | 5.20 Shannon index | 4 | |
| Change in Microbiota Structure at Baseline in FMT Treatment Arm | 2.35 Shannon index | 4 | |
| Change in Microbiota Structure at Week 2 in FMT Treatment Arm | 3.90 Shannon index | 4 | |
| Change in Microbiota Structure at Week 4 in FMT Treatment Arm | 3.85 Shannon index | 4 | |
| Change in Microbiota Structure at Week 8 in FMT Treatment Arm | 3.95 Shannon index | 4 | |
| Change in Microbiota Structure at Week 12 in FMT Treatment Arm | 3.80 Shannon index | 4 |
Number of Treatment-Emergent Serious Adverse Events [Safety and Tolerability]
Baseline Visit, 2 weeks, 4 weeks, 8 weeks, and 12 weeks.
| Group | Value | Interval | Number analysed |
|---|---|---|---|
| Number of Serious AE at Baseline | 0 number of events | 5 | |
| Number of Serious AE at Week 2 | 0 number of events | 5 | |
| Number of Serious AE at Week 4 | 0 number of events | 5 | |
| Number of Serious AE at Week 8 | 0 number of events | 5 | |
| Number of Serious AE at Week 12 | 0 number of events | 5 | |
| Number of Serious AE at Baseline | 0 number of events | 5 | |
| Number of Serious AE at Week 2 | 0 number of events | 5 | |
| Number of Serious AE at Week 4 | 0 number of events | 5 | |
| Number of Serious AE at Week 8 | 0 number of events | 5 | |
| Number of Serious AE at Week 12 | 0 number of events | 5 |
Number of Treatment-Emergent Non-Serious Adverse Events [Safety and Tolerability]
Baseline Visit, 2 weeks, 4 weeks, 8 weeks, and 12 weeks.
| Group | Value | Interval | Number analysed |
|---|---|---|---|
| Number of Non-serious AE at Baseline | 1 Number of events | 5 | |
| Number of Non-serious AE at Week 2 | 0 Number of events | 5 | |
| Number of Non-serious AE at Week 4 | 0 Number of events | 5 | |
| Number of Non-serious AE at Week 8 | 0 Number of events | 5 | |
| Number of Non-serious AE at Week 12 | 0 Number of events | 5 | |
| Number of Non-serious AE at Baseline | 0 Number of events | 5 | |
| Number of Non-serious AE at Week 2 | 0 Number of events | 5 | |
| Number of Non-serious AE at Week 4 | 0 Number of events | 5 | |
| Number of Non-serious AE at Week 8 | 0 Number of events | 5 | |
| Number of Non-serious AE at Week 12 | 0 Number of events | 5 |
Values as posted on ClinicalTrials.gov. Outcomes measured differently across trials are not directly comparable.
Safety
| Group | Participants at risk | Serious adverse events | Deaths |
|---|---|---|---|
| Number of Events at 12 Weeks for Interventional FMT Treatment Arm | 4 | 0 (0.0%) | 0 |
| Number of Events at 36 Weeks for Interventional FMT Treatment Arm | 4 | 0 (0.0%) | 0 |
| Number of Events at 12 Weeks for Observational Control Arm | 1 | 0 (0.0%) | 0 |
As posted on ClinicalTrials.gov. Serious adverse events include any serious health event during the trial, whether or not the treatment caused it.
What it measured
Main measures
Participants Who Complete the Study Protocol
Baseline through week 48
SafetyChange in Fecal Microbiota
Baseline Visit, 2 weeks, 4 weeks, 8 weeks, and 12 weeks.
Number of Treatment-Emergent Serious Adverse Events [Safety and Tolerability]
Baseline Visit, 2 weeks, 4 weeks, 8 weeks, and 12 weeks.
SafetyNumber of Treatment-Emergent Non-Serious Adverse Events [Safety and Tolerability]
Baseline Visit, 2 weeks, 4 weeks, 8 weeks, and 12 weeks.
Safety
Other measures (12)
Change in Plasma CD19+ B Cells in Interventional Arm [CD19: Cluster of Differentiation Antigen 19]
Baseline Visit, 2 weeks, 4 weeks, 8 weeks, and 12 weeks.
Immune responseChange in Plasma CD19+ B Cells in Observational Arm
Baseline Visit, 2 weeks, 4 weeks, 8 weeks, and 12 weeks.
Immune responseChange in Serum IgA Immunoglobulin Levels in Interventional Arm [IgA: Immunoglobulin A]
Baseline Visit, 2 weeks, 4 weeks, 8 weeks, and 12 weeks.
Change in Serum IgA Immunoglobulin Levels in Observational Arm
Baseline Visit, 2 weeks, 4 weeks, and 12 weeks.
Change in Serum IgM Immunoglobulin Levels in Interventional Arm [IgM: Immunoglobulin M]
Baseline Visit, 2 weeks, 4 weeks, 8 weeks and 12 weeks.
Change in Serum IgM Immunoglobulin Levels in Observational Arm
Baseline Visit, 2 weeks, 4 weeks, 8 weeks and 12 weeks.
Change in Serum IgG Immunoglobulin Levels in Interventional Arm [IgG: Immunoglobulin G]
Baseline Visit, 2 weeks, 4 weeks, 8 weeks and 12 weeks
Change in Serum IgG Immunoglobulin Levels in Observational Arm
Baseline Visit, 2 weeks, 4 weeks, 8 weeks and 12 weeks
Incidence of New T2/FLAIR Lesions
At pre-treatment visit and week 12.
MRI lesionsTreatment-emergent Gadolinium Enhancing Lesions
At pre-treatment visit and week 12.
MRI lesions
Who could take part
Relapsing MS · 18 to 60
Show the full criteria
Inclusion criteria
1. Age 18-60 inclusive (at time of screening). 2. Diagnosis of relapsing-remitting multiple sclerosis (MS) by the International Panel McDonald Criteria (2010)(1), incorporating 2017 revisions, which reclassify select high-risk Clinically Isolated Syndromes under 2010 criteria as RRMS under 2017 criteria, and Lublin criteria (2014)(2). [RRMS: relapsing remitting multiple sclerosis] 3. Recent documented MS disease activity, defined as at least 1 clinical relapse within the past 1 year prior to baseline OR 2 clinical relapses in the past 2 years prior to baseline OR at least 1 new T2/FLAIR lesion on brain or spine MRI OR at least 1 gadolinium enhancing lesion on brain or spine MRI in the past 1 year prior to baseline. 4. Expanded Disability Status Scale (EDSS) less than or equal to 6.0; EDSS 5.5 or less if MS disease duration is greater than 15 years (no other disease duration restriction). 5. Must have positive serology for Epstein-Barr Virus (EBV) (IgG anti-EBNA positive) at screening, indicating prior exposure. [EBNA: Epstein-Barr nuclear antigen] 6. No prior MS disease-modifying therapy or a 12-week washout period for participants on glatiramer acetate or interferon-beta therapy. 7. At least 4 weeks from baseline since last use of IV or oral glucocorticoids. Protocol: MS-BIOME Study. 8. Agree to maintain a stable diet during the course of the study (over-the-counter probiotics are allowable). 9. Premenopausal women and women \<12 months after the onset of menopause must have a negative serum pregnancy test unless they have undergone surgical sterilization. 10. Female participants of childbearing potential who are sexually active with a non-sterilized male partner must agree to use a highly effective method of contraception; non-sterilized male participants who are sexually active with a female partner of childbearing potential must agree to use a highly effective method of contraception. 11. Not actively participating in another interventional MS clinical trial (participation in other observational research studies is allowable).
Exclusion criteria
1. Prior use of fingolimod, dimethyl fumarate, teriflunomide, natalizumab, alemtuzumab, mitoxantrone, cyclophosphamide, rituximab, ocrelizumab, daclizumab, methotrexate, azathioprine, mycophenolate mofetil, cyclosporine, leflunomide, or induction chemotherapy. 2. No use of diuretics like furosemide (Lasix) 1 week before the first dose of oral antibiotics. The use of hydrochlorothiazide (HCTZ) for hypertension at a dose \< 50 mg/day is allowable. 3. Progressive MS by Lublin criteria (2014). 4. No oral or IV antibiotics are allowed within 8 weeks prior to screening and within 12 weeks prior to the planned FMT procedure (for participants in the FMT arm) or prior to the first stool collection (for participants in the control arm). (Note that topical, otic, ocular antibiotics are specifically allowable, which is consistent with the IMSMS.org protocol for collaborative gut microbiome research in MS). [IMSMS: International MS Microbiome Study] 5. Hypersensitivity or allergy to study antibiotics, conscious sedation medications, or bowel preparation. 6. Contraindication to study procedures, including MRI, anesthesia (ASA criteria IV and V), colonoscopy, and phlebotomy. 7. History of inflammatory bowel disease (Crohn's Disease, Ulcerative Colitis) Protocol: MS-BIOME Study. 8. Active symptomatic C. Difficile infection (colonization is not an exclusion). 9. Active gastrointestinal condition being investigated (i.e. GI bleeding, colon cancer, active GI workup); history of known or suspected toxic megacolon and/or known small bowel ileus, major gastrointestinal surgery (e.g. significant bowel resection) within 3 months before enrollment (note that this does not include appendectomy or cholecystectomy); or history of total colectomy or bariatric surgery. 10. History of malignancy (except excised cutaneous basal cell carcinoma or squamous cell carcinoma, which are allowable), including no concurrent induction chemotherapy, radiation therapy, or biological treatment for active malignancy. 11. Pregnant or lactating women or intention of getting pregnant during the trial period. 12. Active infection, including untreated latent or active tuberculosis, HIV, hepatitis, syphilis, or other major active infection. 13. Known immunodeficiency, including Common Variable Immunodeficiency (CVID). 14. INR>1.5, Platelets\<100, Hemoglobin \<8.5, WBC\<2.0, Absolute lymphocyte count \<0.8, Absolute Neutrophil Count \<0.5, CD4\<200, eGFR\<45. [INR: international normalized ratio, WBC: White Blood cell, CD4: cluster of differentiation 4, eGFR: epidermal growth factor receptor] 15. Any condition that in the opinion of the study PI could jeopardize the safety of the participant, would make it unlikely for the participant to complete the study or could confound the results of the study. 16. Unable or unwilling to comply with study protocol requirements.
As registered. Criteria can change, so ask the trial team or your neurologist.
About this trial
In the sponsor's words
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.
Papers
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/pnasBackground
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.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.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.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.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.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.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.2015.18Background
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.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 3
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History
Started
Nov 2018
Main results due
Dec 2024
Finished
Dec 2024
Results posted
Feb 2026