Fecal Microbiota Transplantation (FMT) in Multiple Sclerosis

October 7, 2020 updated by: Ali Keshavarzian, Rush University Medical Center

Single-Arm, Non-Randomized, Time Series, Single-Subject Study: Fecal Microbiota Transplantation (FMT) in Multiple Sclerosis

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

A subject (n-of-1) clinically diagnosed with Relapsing Remitting Multiple Sclerosis (RRMS), by Rush University Neurologists, volunteered and provided written informed consent to participate in this study conducted by Rush University Medical Center's department of Digestive Diseases and Nutrition. The RRMS subject underwent a fecal microbiota transplantation (FMT) administered outside the United States, at Taymount Clinic in the Bahamas, for the treatment of their MS. Being one of the investigators' patients, the subject volunteered to donate their stool samples to the Rush University Medical Center Gastrointestinal (GI) tissue repository for microbiota interrogation at the following time points: before FMT (baseline), 3, 13, 26, 39, 52 weeks (1 year) after FMT, to determine the impact on their microbiota composition and sustainability of the change. The subject also agreed to donate their blood during the above stated time points to see if FMT affected markers of bacteria translocation and systemic inflammation. The subject also agreed to have their GI symptoms, diet, sleep, and MS related symptoms (rating scales or questionnaires), MRI (brain & spine), as well as their gait metric activity objectively assessed to see if the FMT affects these symptoms and whether any observed improvement is sustained, in this proof-of-concept study. Based on this research, the investigators hypothesize that the FMT will significantly altered the overall microbial community structure to promote the growth of short chain fatty acid (SCFA)-producing beneficial bacteria, which in turn could potentially improve the MS subject's health outcomes, neurological symptoms, and walking metrics over time. More clinical trials (larger sample size) will be needed to study the potential of FMT for the treatment of MS and to examine the long term effects. FMT is an emerging treatment approach for MS. The donor selection, the separation of fecal bacteria, the frequency of FMT, the way of infusion, the long-term safety, and efficacy are still uncertain and need to be examined.

Study Type

Observational

Enrollment (Actual)

1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Illinois
      • Chicago, Illinois, United States, 60612
        • Rush University Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

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.

Description

Inclusion Criteria:

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

Exclusion Criteria:

  1. Newly diagnosed multiple sclerosis.
  2. Inactive relapsing-remitting multiple sclerosis (RRMS).
  3. Unstable or no MS therapy/medication use.
  4. 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)).
  5. 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
  6. Severe malnutrition or obesity with BMI ˃ 40.
  7. Antibiotic and probiotic use (except yogurt) within 4 weeks of enrollment.
  8. 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.
  9. Pregnant or lactating women or intention of getting pregnant during the trial period.
  10. Active infection including untreated latent or active tuberculosis, HIV, hepatitis, syphilis or other major active infection.
  11. Active symptomatic C. Difficile infection (colonization is not an exclusion).
  12. 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Case-Only
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
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)
Longitudinal FMT study: Baseline, 3 week, 13 week, 26 week, 39 week, 52 week
Other Names:
  • Taymount Clinic

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Fecal microbial community structure and functional changes over six time frames for phylum, genus and species taxonomic level bacteria, virus, fungi, and archaea.
Time Frame: Baseline, 3 week, 13 week, 26 week, 39 week, 52 week
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).
Time Frame: Baseline, 3 week, 13 week, 52 week
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).
Time Frame: Baseline, 3 week, 13 week, 52 week
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).
Time Frame: Baseline, 3 week, 13 week, 52 week
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).
Time Frame: Baseline, 3 week, 13 week, 52 week
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).
Time Frame: Baseline, 3 week, 13 week, 52 week
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).
Time Frame: Baseline, 3 week, 13 week, 52 week
Orthopedic gait task, side gaze gait, and alternating gaze gait metrics.
Baseline, 3 week, 13 week, 52 week

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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).
Time Frame: Baseline, 3 week, 13 week, 26 week, 39 week, 52 week
Targeted metabolomics of short-chain-fatty-acids (SCFA).
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.
Time Frame: Baseline, 3 week, 13 week, 26 week, 39 week, 52 week
ELISA (enzyme-linked immunosorbent assay)
Baseline, 3 week, 13 week, 26 week, 39 week, 52 week
Sleep changes over six time frames.
Time Frame: Baseline, 3 week, 13 week, 26 week, 39 week, 52 week
Munich ChronoType Questionnaire (MCTQ). Questions about work day and free day sleep schedules, work details, and lifestyle provide data to aid in the understanding of how biological clocks work in social life, such as Roenneberg's conclusions of social jetlag. The MCTQ categorizes each participant into one of seven chronotype groups, and utilizes data on participants' midsleep phase and sleep debt to survey what "type" of sleeper each person is.
Baseline, 3 week, 13 week, 26 week, 39 week, 52 week
Food timing changes over six time frames.
Time Frame: Baseline, 3 week, 13 week, 26 week, 39 week, 52 week
Food Timing Screener (FTS) questionnaire. A structured food demographics questionnaire was therefore developed to access food timing. The questionnaire consists of eight questions asking subjects' eating habits on work days and non-work days. Questions include the time of the main meal during work and non-work days, time of last meal before bed, consistency of dinner within work and non-work days, and consistency of breakfast, lunch, and dinner between work and non-work days.
Baseline, 3 week, 13 week, 26 week, 39 week, 52 week
Gastrointestinal symptoms changes over six time frames (t-scores, mean, standard deviations).
Time Frame: Baseline, 3 week, 13 week, 26 week, 39 week, 52 week
Patient-Reported Outcomes Measurements Information System (PROMIS) gastrointestinal questionnaire for Belly Pain (6 questions), Bowel Incontinence (4 questions), Constipation (9 questions), and Gas & Bloating (12 questions). Higher score denoted more GI symptoms. Lower score denotes less GI symptoms. Scores range from 20 (low) to 80 (high). A score of 50 is denoted as the general population.
Baseline, 3 week, 13 week, 26 week, 39 week, 52 week
Walking changes over six time frames.
Time Frame: Baseline, 3 week, 13 week, 26 week, 39 week, 52 week
Multiple sclerosis walking scale questionnaire. Higher scores indicate a greater impact from MS on walking than lower scores. Scale range from 1 (no impact) to 5 (high impact). 12 questions in total.
Baseline, 3 week, 13 week, 26 week, 39 week, 52 week
Lesions changes over three time frames.
Time Frame: Baseline, 26 week and 52 week
MRI of brain and spine
Baseline, 26 week and 52 week
Food and frequency of consumption changes over six time frames.
Time Frame: Baseline, 3 week, 13 week, 26 week, 39 week, 52 week
Food Time Questionnaire (FTQ) consists of a list of foods and the frequency in which these foods are consumed in at each time frame.
Baseline, 3 week, 13 week, 26 week, 39 week, 52 week
Single day food recall changes over six time frames.
Time Frame: Baseline, 3 week, 13 week, 26 week, 39 week, 52 week
Automated Self-Administered 24-Hour Recall (ASA24) Dietary Assessment. Total nutrients from all supplements reported in a given day.
Baseline, 3 week, 13 week, 26 week, 39 week, 52 week
Diet changes over six time frames.
Time Frame: Baseline, 3 week, 13 week, 26 week, 39 week, 52 week
Vioscreen Food Frequency Questionnaire (FFQ). Total of 19 measured food components collected for each time frame. Vioscreen captures comprehensive dietary behaviors in just 30 minutes. VioScreen is a unique online dietary questionnaire, management and analysis system that efficiently gathers and manages data, that immediately identify dietary "habits" and counsel for lifestyle changes.
Baseline, 3 week, 13 week, 26 week, 39 week, 52 week
Measurement of blood serum biomarker Interleukin-6 (IL-6) (pg/ml) changes over six time frames.
Time Frame: Baseline, 3 week, 13 week, 26 week, 39 week, 52 week
ELISA (enzyme-linked immunosorbent assay)
Baseline, 3 week, 13 week, 26 week, 39 week, 52 week
Measurement of blood serum biomarker Interleukin-* (IL-8) (pg/ml) changes over six time frames.
Time Frame: Baseline, 3 week, 13 week, 26 week, 39 week, 52 week
ELISA (enzyme-linked immunosorbent assay)
Baseline, 3 week, 13 week, 26 week, 39 week, 52 week
Measurement of blood serum biomarker Tumor necrosis factor alpha (TNFα) (pg/ml) changes over six time frames.
Time Frame: Baseline, 3 week, 13 week, 26 week, 39 week, 52 week
ELISA (enzyme-linked immunosorbent assay)
Baseline, 3 week, 13 week, 26 week, 39 week, 52 week

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Rush University Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 25, 2018

Primary Completion (Actual)

April 1, 2020

Study Completion (Actual)

May 1, 2020

Study Registration Dates

First Submitted

May 28, 2019

First Submitted That Met QC Criteria

June 3, 2019

First Posted (Actual)

June 5, 2019

Study Record Updates

Last Update Posted (Actual)

October 8, 2020

Last Update Submitted That Met QC Criteria

October 7, 2020

Last Verified

October 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 18082009

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Undecided

IPD Plan Description

It is not yet known if there will be a plan to make IPD available. This pilot study of FMT in a patient with multiple sclerosis (MS) could suggest a potential effective treatment. More clinical trials (larger sample size) will be needed to study the potential of FMT for the treatment of MS and it's long term effects in the future.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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