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Fecal Microbial Transplantation in Relapsing Multiple Sclerosis Patients

Primary Purpose

Autoimmune Diseases, Relapsing Multiple Sclerosis

Status

Terminated

Phase

Phase 2

Locations

Canada

Study Type

Interventional

Intervention

Fecal microbiota

About this trial

This is an interventional treatment trial for Autoimmune Diseases focused on measuring microbiome, multiple sclerosis, microbiota, gut

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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

Exclusion Criteria:

Not meeting all of the above inclusion criteria
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

Sites / Locations

London Health Sciences Centre, University Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Arm Label

Early Intervention

Late Intervention

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Evaluate Effect of Fecal Microbial Transplantation in Gut Microbiome

PCR (polymerase chain reaction) to assess blood DNA bacteria

Evaluate Effect of Fecal Microbial Transplantation in Gut Permeability

Urinalysis to evaluate lactulose and mannitol levels

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

Neurological exam using the Expanded Disability Status Scale

Evaluate Treatment Safety: MRI to Access Subclinical Disease Activity

MRI to access subclinical disease activity

Full Information

NCT ID

NCT03183869

First Posted

May 9, 2017

Last Updated

November 12, 2019

Sponsor

Lawson Health Research Institute

1. Study Identification

Unique Protocol Identification Number

NCT03183869

Brief Title

Fecal Microbial Transplantation in Relapsing Multiple Sclerosis Patients

Official Title

Fecal Microbial Transplantation in Relapsing Multiple Sclerosis Patients

Study Type

Interventional

2. Study Status

Record Verification Date

November 2019

Overall Recruitment Status

Terminated

Why Stopped

Primary Investigator passed away.

Study Start Date

August 24, 2017 (Actual)

Primary Completion Date

November 19, 2018 (Actual)

Study Completion Date

January 25, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Lawson Health Research Institute

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Autoimmune Diseases, Relapsing Multiple Sclerosis

Keywords

microbiome, multiple sclerosis, microbiota, gut

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Crossover Assignment

Model Description

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.

Masking

None (Open Label)

Allocation

Randomized

Enrollment

14 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Early Intervention

Arm Type

Active Comparator

Arm Description

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.

Arm Title

Late Intervention

Arm Type

Active Comparator

Arm Description

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.

Intervention Type

Drug

Intervention Name(s)

Fecal microbiota

Other Intervention Name(s)

fecal microbial transplantation

Intervention Description

fecal microbial transplantation

Primary Outcome Measure Information:

Title

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

Description

Time Frame

Within 6 months

Secondary Outcome Measure Information:

Title

Evaluate Effect of Fecal Microbial Transplantation in Gut Microbiome

Description

PCR (polymerase chain reaction) to assess blood DNA bacteria

Time Frame

Monthly for 6 months

Title

Evaluate Effect of Fecal Microbial Transplantation in Gut Permeability

Description

Urinalysis to evaluate lactulose and mannitol levels

Time Frame

Baseline, 6 months, 12 months

Title

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

Description

Neurological exam using the Expanded Disability Status Scale

Time Frame

Monthly for 6 months

Title

Evaluate Treatment Safety: MRI to Access Subclinical Disease Activity

Description

MRI to access subclinical disease activity

Time Frame

Baseline, 6 months and 12 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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 Exclusion Criteria: Not meeting all of the above inclusion criteria 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Marcelo Kremenchutzky, MD, FRCP

Organizational Affiliation

London Health Science Centre

Official's Role

Principal Investigator

Facility Information:

Facility Name

London Health Sciences Centre, University Hospital

City

London

State/Province

Ontario

ZIP/Postal Code

N6A 5A5

Country

Canada

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

25775034

Citation

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Results Reference

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Results Reference

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PubMed Identifier

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Citation

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Fecal Microbial Transplantation in Relapsing Multiple Sclerosis Patients

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