Fecal Microbial Transplantation in Relapsing Multiple Sclerosis Patients

NCT ID: NCT03183869

Last Updated: 2019-12-02

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 14 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-08-24
• Study Completion Date: 2019-01-25

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.

Detailed Description

At Visit 1, before FMT(fecal microbial transplantation), patients will be evaluated for their vital signs, medical history and concomitant medications. Also before transplantation, patient's stool will be collected to study their microbial profile, blood collected for analysis to evaluate cytokines levels as well as blood DNA bacteria and finally, urinalysis to assess gut permeability (baseline). Other assessments (prior to the first dose of therapy) include an Expanded Disability Status Scale (EDSS), pregnancy test (if applicable), physical exam and ECG. Blood samples are also taken at month 1 in order to establish a baseline for routine chemistry/hematology. After all these assessments FMT will be performed by a trained nurse via a rectal enema.

FMT for the early intervention group will be at V1, 2, 2.1, 2.2, V3 and V4. FMT randomized to late intervention group will be V4, 5, 6, 6.1.6.2, 6.3 and V7

Both groups, at Visit 1, Visit 4 and Visit 7, patients will be instructed to drink lactulose solution and collect the urine throughout the previous night and first thing in the morning. A proper collecting bottle will be provided and will also undergo a contrast-enhanced brain MRI scan at Robarts Institute London Ontario.

Those randomized to the Early Intervention group, will return to the clinic for visit 2, 1 month after the first FMT(fecal microbial transplantation). Another stool sample to evaluate the microbial before the second FMT will be collected and peripheral blood samples for cytokines and blood bacterial DNA analysis. Both groups this same routine procedure repeated at visits 2.1, 2.2, 3, 4, 5, 6, 6.1.6.2, 6.3 and visit 7. Another safety assessment 2 weeks after FMT is to review any adverse events that may have occurred.

Both groups will have an MRI at M1, M6 and M12.

Conditions

Autoimmune Diseases; Relapsing Multiple Sclerosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Early Intervention

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.

Group Type: ACTIVE_COMPARATOR

Fecal microbiota

Intervention Type: DRUG

fecal microbial transplantation

Late Intervention

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.

Group Type: ACTIVE_COMPARATOR

Fecal microbiota

Intervention Type: DRUG

fecal microbial transplantation

Interventions

Fecal microbiota

fecal microbial transplantation

Intervention Type: DRUG

Other Intervention Names

fecal microbial transplantation

Eligibility Criteria

Inclusion Criteria

• 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

• Pregnancy or breastfeeding
• Current or recent [in the last 90 days] exposure to high dose corticosteroids
• Ongoing use of antibiotics
• Standard of care exclusions for MRI scans
• 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
• Any contra-indications for MRI. Participants are to be screened by a CMRTO (The College of Medical Radiation Technologists of Ontario) certified MRI Technologist in order to determine the MRI compatibility or exclusion of implantable/external devices according to the manufacturer's safety guidelines. The devises include cerebral aneurysm clips, neuro-stimulator, mechanical heart valves, cardiac stents, IUDs(intrauterine device), vena cava filters, shunts, embolization coils, cochlear implants, non-removable prosthesis/artificial limbs. Contraindications are pacemaker of defibrillator, shrapnel/metallic fragments, previous brain surgery, seizure, severe claustrophobia, weight or body index that will prevent a successful MRI study

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

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

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Marcelo Kremenchutzky, MD, FRCP

Role: PRINCIPAL_INVESTIGATOR

London Health Science Centre

Locations

London Health Sciences Centre, University Hospital

London, Ontario, Canada

Countries

Canada

References

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Reference Type: BACKGROUND

PMID: 25775034 (View on PubMed)

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Reference Type: BACKGROUND

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Reference Type: BACKGROUND

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Reference Type: BACKGROUND

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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.

Reference Type: BACKGROUND

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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.

Reference Type: BACKGROUND

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Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

MS-FMT-001

Identifier Type: -

Identifier Source: org_study_id