Fecal Microbial Transplantation in Relapsing Multiple Sclerosis Patients

NCT03183869 | Terminated Phase 2 Results

• 1 other identifier: MS-FMT-001
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief Summary

The proposed randomized, open label, with treat as usual control group (standard treatment or any disease modifying drugs), crossover phase II study will be conducted in 40 patients (n=20 per group) with the relapsing forms of multiple sclerosis according to the McDonald 2010 Criteria. Patients will be randomized into 2 intervention groups. One will receive the FMT from month 1 and for the first 6 months (early intervention group). On the other hand, the other group will be a control group during the first 6 months and will receive the FMT for the last 6 months of the study. Patients will be screened for eligibility based on MS diagnosis and EDSS and if eligible then consented. All qualified patients will not be currently or recently treated with high dose steroids.

Conditions

Autoimmune Diseases; Relapsing Multiple Sclerosis

Keywords

microbiome; multiple sclerosis; microbiota; gut

Outcome Measures

Primary Outcomes (1)

• Effect of Fecal Microbial Transplantation in Peripheral Blood Cytokines Within Relapsing Multiple Sclerosis Patients

  Luminex test to evaluate the levels of 25 cytokines in peripheral blood pre-fecal transplant and post fecal transplant. Due to early termination of the trial, we didn't meet the number of participants required for statistical analysis; therefore, we analyzed the data pre and post FMT, rather than early and late intervention groups as originally planned. Due to the small sample size there was a large variation between cytokine levels of each participant for pre and post FMT, resulting in large standard deviations.

  Within 6 months

Secondary Outcomes (4)

• Evaluate Effect of Fecal Microbial Transplantation in Gut Microbiome

  Monthly for 6 months

• Evaluate Effect of Fecal Microbial Transplantation in Gut Permeability

  Baseline, 6 months, 12 months

• Evaluate Treatment Clinical Safety: Neurological Exam Using the Expanded Disability Status Scale

  Monthly for 6 months

• Evaluate Treatment Safety: MRI to Access Subclinical Disease Activity

  Baseline, 6 months and 12 months

Study Arms (2)

Early Intervention

ACTIVE COMPARATOR

Fecal microbiota via enema at Month 1, 2, 3. 4, 5 and month 6 along with stool, urine and blood collection. At months 7, 8, 9, 10, 11 and 12 only stool, urine and blood collection.

Drug: Fecal microbiota

Late Intervention

ACTIVE COMPARATOR

At months 1, 2, 3, 4, 5 and 6, stool, urine and blood collection. Fecal microbiota via enema at month 6, 7, 8, 9, 10, 11and 12 months along with stool, urine and blood collection.

Drug: Fecal microbiota

Interventions

Fecal microbiota DRUG

fecal microbial transplantation

Also known as: fecal microbial transplantation

Early Intervention; Late Intervention

Eligibility Criteria

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

You may qualify if:

• Have a confirmed diagnosis of relapsing MS defined by the 2010 Revised McDonald Criteria for the Diagnosis of Multiple Sclerosis
• Any disease duration will be accepted.
• Have a baseline EDSS of = or \<7.0
• Older than 18 years of age.
• Be able to attend all clinic appointments without interruption
• Patients must be able to understand English sufficiently well to understand and comply with the clinic and medication schedules and procedures.
• Be willing and able to give written informed consent
• Negative blood pregnancy test at screening

You may not qualify if:

• Pregnancy or breastfeeding
• Current or recent \[in the last 90 days\] exposure to high dose corticosteroids
• Ongoing use of antibiotics
• Presence of a chronic intestinal disease e.g. Celiac, malabsorption, colonic tumor
• Inability to provide informed written consent.
• Immunosuppression from transplantation, HIV, cancer chemotherapy or ongoing use of any immunosuppressive agents.
• Concomitant inflammatory diseases
• Pregnant women

Sponsors & Collaborators

• London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's: lead

Study Sites (1)

London Health Sciences Centre, University Hospital

London, Ontario, N6A 5A5, Canada

Location

Related Publications (9)

• Cantarel BL, Waubant E, Chehoud C, Kuczynski J, DeSantis TZ, Warrington J, Venkatesan A, Fraser CM, Mowry EM. Gut microbiota in multiple sclerosis: possible influence of immunomodulators. J Investig Med. 2015 Jun;63(5):729-34. doi: 10.1097/JIM.0000000000000192.

  PMID: 25775034 BACKGROUND

• Miyake S, Kim S, Suda W, Oshima K, Nakamura M, Matsuoka T, Chihara N, Tomita A, Sato W, Kim SW, Morita H, Hattori M, Yamamura T. Dysbiosis in the Gut Microbiota of Patients with Multiple Sclerosis, with a Striking Depletion of Species Belonging to Clostridia XIVa and IV Clusters. PLoS One. 2015 Sep 14;10(9):e0137429. doi: 10.1371/journal.pone.0137429. eCollection 2015.

  PMID: 26367776 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

• Lavasani S, Dzhambazov B, Nouri M, Fak F, Buske S, Molin G, Thorlacius H, Alenfall J, Jeppsson B, Westrom B. A novel probiotic mixture exerts a therapeutic effect on experimental autoimmune encephalomyelitis mediated by IL-10 producing regulatory T cells. PLoS One. 2010 Feb 2;5(2):e9009. doi: 10.1371/journal.pone.0009009.

  PMID: 20126401 BACKGROUND

• Kelly CR, de Leon L, Jasutkar N. Fecal microbiota transplantation for relapsing Clostridium difficile infection in 26 patients: methodology and results. J Clin Gastroenterol. 2012 Feb;46(2):145-9. doi: 10.1097/MCG.0b013e318234570b.

  PMID: 22157239 BACKGROUND

• Kwon HK, Kim GC, Kim Y, Hwang W, Jash A, Sahoo A, Kim JE, Nam JH, Im SH. Amelioration of experimental autoimmune encephalomyelitis by probiotic mixture is mediated by a shift in T helper cell immune response. Clin Immunol. 2013 Mar;146(3):217-27. doi: 10.1016/j.clim.2013.01.001. Epub 2013 Jan 16.

  PMID: 23416238 BACKGROUND

• Mielcarz DW, Kasper LH. The gut microbiome in multiple sclerosis. Curr Treat Options Neurol. 2015 Apr;17(4):344. doi: 10.1007/s11940-015-0344-7.

  PMID: 25843302 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

• Wang S, Xu M, Wang W, Cao X, Piao M, Khan S, Yan F, Cao H, Wang B. Systematic Review: Adverse Events of Fecal Microbiota Transplantation. PLoS One. 2016 Aug 16;11(8):e0161174. doi: 10.1371/journal.pone.0161174. eCollection 2016.

  PMID: 27529553 BACKGROUND

MeSH Terms

Conditions

Autoimmune Diseases; Multiple Sclerosis

Interventions

Fecal Microbiota Transplantation

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Biological Therapy; Therapeutics

Results Point of Contact

• Title: Chantelle Graf, RN
• Organization: Lawson Health Research Institute

chantelle.graf@sjhc.london.on.ca

519-685-8500

Study Officials

• Marcelo Kremenchutzky, MD, FRCP

  London Health Science Centre

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a prospective, cross-over, open label, randomized 1:1 early versus delayed groups, interventional \[FMT\] versus no interventional \[no FMT\] controlled trial to explore the effects of FMT from a healthy donor to RMS patients and investigate whether this can influence disease activity based on a panel of biological markers.

Study Record Dates

• First Submitted: May 9, 2017
• First Posted: June 12, 2017
• Study Start: August 24, 2017
• Primary Completion: November 19, 2018
• Study Completion: January 25, 2019
• Last Updated: December 2, 2019
• Results First Posted: December 2, 2019

Record last verified: 2019-11

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)