Fecal Microbiota Transplantation (FMT) of FMP30 in Relapsing-Remitting Multiple Sclerosis

NCT03594487 | Terminated Phase 1 Results FDA Drug

• 1 other identifier: 17-23827
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Relapsing Remitting Multiple Sclerosis

Keywords

Multiple Sclerosis; Relapsing Remitting Multiple Sclerosis; Fecal Microbiota Transplantation

Outcome Measures

Primary Outcomes (4)

• 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.

  Baseline Visit, 2 weeks, 4 weeks, 8 weeks, and 12 weeks.

Secondary Outcomes (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.

• Change in Plasma CD19+ B Cells in Observational Arm

  Baseline Visit, 2 weeks, 4 weeks, 8 weeks, and 12 weeks.

• Change 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.

Study Arms (2)

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).

Drug: FMP30 Donor Stool; Procedure: Fecal Microbiota Transplantation (FMT) of FMP30 Donor Stool

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.

Other: Observational Control

Interventions

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.

Interventional FMT Treatment Arm

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.

Observational Control Arm

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.

Interventional FMT Treatment Arm

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Age 18-60 inclusive (at time of screening).
• 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). \[RRMS: relapsing remitting multiple sclerosis\]
• 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.
• 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).
• Must have positive serology for Epstein-Barr Virus (EBV) (IgG anti-EBNA positive) at screening, indicating prior exposure. \[EBNA: Epstein-Barr nuclear antigen\]
• No prior MS disease-modifying therapy or a 12-week washout period for participants on glatiramer acetate or interferon-beta therapy.
• At least 4 weeks from baseline since last use of IV or oral glucocorticoids. Protocol: MS-BIOME Study.
• Agree to maintain a stable diet during the course of the study (over-the-counter probiotics are allowable).
• Premenopausal women and women \<12 months after the onset of menopause must have a negative serum pregnancy test unless they have undergone surgical sterilization.
• 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.
• Not actively participating in another interventional MS clinical trial (participation in other observational research studies is allowable).

You may not qualify if:

• Prior use of fingolimod, dimethyl fumarate, teriflunomide, natalizumab, alemtuzumab, mitoxantrone, cyclophosphamide, rituximab, ocrelizumab, daclizumab, methotrexate, azathioprine, mycophenolate mofetil, cyclosporine, leflunomide, or induction chemotherapy.
• 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.
• Progressive MS by Lublin criteria (2014).
• 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). \[IMSMS: International MS Microbiome Study\]
• Hypersensitivity or allergy to study antibiotics, conscious sedation medications, or bowel preparation.
• Contraindication to study procedures, including MRI, anesthesia (ASA criteria IV and V), colonoscopy, and phlebotomy.
• History of inflammatory bowel disease (Crohn's Disease, Ulcerative Colitis) Protocol: MS-BIOME Study.
• 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.
• 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.
• Pregnant or lactating women or intention of getting pregnant during the trial period.
• Active infection, including untreated latent or active tuberculosis, HIV, hepatitis, syphilis, or other major active infection.
• Known immunodeficiency, including Common Variable Immunodeficiency (CVID).
• 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. \[INR: international normalized ratio, WBC: White Blood cell, CD4: cluster of differentiation 4, eGFR: epidermal growth factor receptor\]
• 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.
• Unable or unwilling to comply with study protocol requirements.

Sponsors & Collaborators

• Jeffrey Gelfand: lead

Study Sites (1)

UCSF Multiple Sclerosis Center

San Francisco, California, 94158, United States

Location

Related Publications (10)

• 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.

  PMID: 28893978 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.

  PMID: 28531908 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.

  PMID: 25607761 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.

  PMID: 27000242 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.

  PMID: 28462225 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.

  PMID: 24018052 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.

  PMID: 27352007 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.

  PMID: 26757463 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.

  PMID: 28422836 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.

  PMID: 28586116 BACKGROUND

MeSH Terms

Conditions

Multiple Sclerosis, Relapsing-Remitting; Multiple Sclerosis

Interventions

Fecal Microbiota Transplantation

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Biological Therapy; Therapeutics

Limitations and Caveats

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.

Results Point of Contact

• Title: Dr. Jeffrey Gelfand, MD, MAS
• Organization: University of California, San Francisco

Jeffrey.Gelfand@ucsf.edu

415-353-2069

Study Officials

• Jeffrey Gelfand, MD, MAS

  UCSF Multiple Sclerosis Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Clinical Neurology

Study Record Dates

• First Submitted: June 7, 2018
• First Posted: July 20, 2018
• Study Start: November 16, 2018
• Primary Completion: December 16, 2024
• Study Completion: December 16, 2024
• Last Updated: February 3, 2026
• Results First Posted: February 3, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: After initial study results are published and on a case by case basis.
• Access Criteria: 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.

Locations

US (1)