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

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.

Timeline

Start

2018-11-16

Primary completion

2024-12-16

Completion

2024-12-16

Outcome

Outcome not reported

Stopped (Enrollment): “Under-enrollment, including after interruption due to a hold on source FMT material and the COVID-19 pandemic”

Publications

• 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.
• 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.
• 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.2015.18098.
• 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.
• 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.

Drugs

Indications