Fecal Microbiota Transplantation (FMT) in Multiple Sclerosis

NCT03975413 | Completed

• 1 other identifier: 18082009
• Study Type: observational
• Target: 1
• Locations: 1 country
• Sites: 1

Brief Summary

Multiple sclerosis (MS) is a chronic immune central nervous system (CNS) disease of unknown cause. Recent studies suggest that gut microbiota could be a trigger for the neuro-inflammation in MS and abnormal gut microbiota composition has been reported in MS patients. These data provided scientific rationale for microbiota-directed intervention, like stool transplant, for the treatment of MS.

Conditions

Multiple Sclerosis, Relapsing-Remitting

Keywords

FMT; Microbiome; Gait; Longitudinal; Multiple Sclerosis

Outcome Measures

Primary Outcomes (7)

• Fecal microbial community structure and functional changes over six time frames for phylum, genus and species taxonomic level bacteria, virus, fungi, and archaea.

  Shotgun Metagenomics

  Baseline, 3 week, 13 week, 26 week, 39 week, 52 week

• Walking and balance changes over four time frames for stride time (seconds).

  Orthopedic gait task, side gaze gait, and alternating gaze gait metrics.

  Baseline, 3 week, 13 week, 52 week

• Walking and balance changes over four time frames for stride distance (meters).

  Orthopedic gait task, side gaze gait, and alternating gaze gait metrics.

  Baseline, 3 week, 13 week, 52 week

• Walking and balance changes over four time frames for cadence (total number of steps per minute).

  Orthopedic gait task, side gaze gait, and alternating gaze gait metrics.

  Baseline, 3 week, 13 week, 52 week

• Walking and balance changes over four time frames for step width (meters).

  Orthopedic gait task, side gaze gait, and alternating gaze gait metrics.

  Baseline, 3 week, 13 week, 52 week

• Walking and balance changes over four time frames for average pelvis forward velocity (meters per second).

  Orthopedic gait task, side gaze gait, and alternating gaze gait metrics.

  Baseline, 3 week, 13 week, 52 week

• Walking and balance changes over four time frames for pelvis smoothness (pelvis horizontal speed).

  Orthopedic gait task, side gaze gait, and alternating gaze gait metrics.

  Baseline, 3 week, 13 week, 52 week

Secondary Outcomes (13)

• Fecal targeted short-chain-fatty-acid metabolomics concentration changes over six time frames for acetate (mM/kg), propionate (mM/kg), butyrate (mM/kg), and total SCFA (mM/kg).

  Baseline, 3 week, 13 week, 26 week, 39 week, 52 week

• Measurement of blood serum biomarker brain-derived neurotrophic factor (BDNF) (ng/ml) changes over six time frames.

  Baseline, 3 week, 13 week, 26 week, 39 week, 52 week

• Sleep changes over six time frames.

  Baseline, 3 week, 13 week, 26 week, 39 week, 52 week

• Food timing changes over six time frames.

  Baseline, 3 week, 13 week, 26 week, 39 week, 52 week

• Gastrointestinal symptoms changes over six time frames (t-scores, mean, standard deviations).

  Baseline, 3 week, 13 week, 26 week, 39 week, 52 week

Study Arms (1)

N=1 MS patient

Single-Arm, Non-Randomized, Time Series, Single-Subject Study. Observational study of the FMT intervention. Single subject studies are based on repeated observations within an individual over time and are acknowledged as an important research method for generating scientific evidence about the health or behavior of an individual. This design is desirable when the available patient pool is limited and thus it is not optimal to randomize participants to a control arm. The subject serves as his/her own control, rather than using another individual/group.These designs are used primarily to evaluate the effect of a variety of interventions in early stage clinical research development.

Other: Fecal Microbiota Transplantation (FMT)

Interventions

Fecal Microbiota Transplantation (FMT) OTHER

Longitudinal FMT study: Baseline, 3 week, 13 week, 26 week, 39 week, 52 week

Also known as: Taymount Clinic

N=1 MS patient

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

One of the investigators' patients planned to have a fecal microbiota transplant (FMT) for treatment of their MS, at the Taymount Clinic in the Bahamas, volunteered to donate multiple sample collection time points for stool and blood. Additionally, the subject would undergo gait metric activity and MRI (brain \& spine), as well as completing MS rating scales and various GI, diet and sleep clinical questionnaires.

You may qualify if:

• Older than 18 years of age.
• Diagnosis of relapsing-remitting multiple sclerosis (RRMS) by neurology(primary specialist).
• Presence of active lesions on brain or spinal cord MRI, in the past 1 year prior to baseline.
• MS disease duration greater than 1 year.
• Symptomatic (Active RRMS).
• On MS therapy/medication greater than 4 weeks.

You may not qualify if:

• Newly diagnosed multiple sclerosis.
• Inactive relapsing-remitting multiple sclerosis (RRMS).
• Unstable or no MS therapy/medication use.
• Presence of symptomatically active gastrointestinal diseases such as inflammatory bowel disease or celiac disease (except for hemorrhoids, hiatal hernia, or occasional (˂3 times a week) heartburn)).
• Pre-existent organ failure or co-morbidities as these may change GI flora: a) liver disease (cirrhosis or persistently abnormal AST or ALT that are 2X˃ normal); b) kidney disease (creatinine ˃ 2.0mg/dL); c) uncontrolled psychiatric illness; d) clinically active lung disease or decompensated heart failure; e) known HIV infection; f) alcoholism; g) transplant recipients (other than FMT); h) diabetes
• Severe malnutrition or obesity with BMI ˃ 40.
• Antibiotic and probiotic use (except yogurt) within 4 weeks of enrollment.
• Chronic use of NSAIDS. A washout period of 3 weeks is needed before the subject could be enrolled into the study. Low dose aspirin is allowed.
• 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.
• 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.

Sponsors & Collaborators

• Rush University Medical Center: lead

Study Sites (1)

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

Related Publications (15)

• 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

• Berer K, Gerdes LA, Cekanaviciute E, Jia X, Xiao L, Xia Z, Liu C, Klotz L, Stauffer U, Baranzini SE, Kumpfel T, Hohlfeld R, Krishnamoorthy G, Wekerle H. Gut microbiota from multiple sclerosis patients enables spontaneous autoimmune encephalomyelitis in mice. Proc Natl Acad Sci U S A. 2017 Oct 3;114(40):10719-10724. doi: 10.1073/pnas.1711233114. Epub 2017 Sep 11.

  PMID: 28893994 BACKGROUND

• Kaskow BJ, Baecher-Allan C. Effector T Cells in Multiple Sclerosis. Cold Spring Harb Perspect Med. 2018 Apr 2;8(4):a029025. doi: 10.1101/cshperspect.a029025.

  PMID: 29358315 BACKGROUND

• Berer K, Mues M, Koutrolos M, Rasbi ZA, Boziki M, Johner C, Wekerle H, Krishnamoorthy G. Commensal microbiota and myelin autoantigen cooperate to trigger autoimmune demyelination. Nature. 2011 Oct 26;479(7374):538-41. doi: 10.1038/nature10554.

  PMID: 22031325 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

• Kirby TO, Ochoa-Reparaz J. The Gut Microbiome in Multiple Sclerosis: A Potential Therapeutic Avenue. Med Sci (Basel). 2018 Aug 24;6(3):69. doi: 10.3390/medsci6030069.

  PMID: 30149548 BACKGROUND

• Adamczyk-Sowa M, Medrek A, Madej P, Michlicka W, Dobrakowski P. Does the Gut Microbiota Influence Immunity and Inflammation in Multiple Sclerosis Pathophysiology? J Immunol Res. 2017;2017:7904821. doi: 10.1155/2017/7904821. Epub 2017 Feb 20.

  PMID: 28316999 BACKGROUND

• Camara-Lemarroy CR, Metz LM, Yong VW. Focus on the gut-brain axis: Multiple sclerosis, the intestinal barrier and the microbiome. World J Gastroenterol. 2018 Oct 7;24(37):4217-4223. doi: 10.3748/wjg.v24.i37.4217.

  PMID: 30310254 BACKGROUND

• Makkawi S, Camara-Lemarroy C, Metz L. Fecal microbiota transplantation associated with 10 years of stability in a patient with SPMS. Neurol Neuroimmunol Neuroinflamm. 2018 Apr 3;5(4):e459. doi: 10.1212/NXI.0000000000000459. eCollection 2018 Jul. No abstract available.

  PMID: 29619403 BACKGROUND

• Quintana FJ, Prinz M. A gut feeling about multiple sclerosis. Proc Natl Acad Sci U S A. 2017 Oct 3;114(40):10528-10529. doi: 10.1073/pnas.1714260114. Epub 2017 Sep 25. No abstract available.

  PMID: 28973867 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

• Chu F, Shi M, Lang Y, Shen D, Jin T, Zhu J, Cui L. Gut Microbiota in Multiple Sclerosis and Experimental Autoimmune Encephalomyelitis: Current Applications and Future Perspectives. Mediators Inflamm. 2018 Apr 2;2018:8168717. doi: 10.1155/2018/8168717. eCollection 2018.

  PMID: 29805314 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

• 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.

  PMID: 22674334 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Whole Fecal Collection; Fecal DNA Extraction; Blood: frozen serum, plasma \& buffy coat.

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

Study Officials

• Ali Keshavarzian, MD

  Rush University Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor and Director of Digestive Diseases & Nutrition

Study Record Dates

• First Submitted: May 28, 2019
• First Posted: June 5, 2019
• Study Start: September 25, 2018
• Primary Completion: April 1, 2020
• Study Completion: May 1, 2020
• Last Updated: October 8, 2020

Record last verified: 2020-10

Locations

US (1)