Clinical trial NCT03975413: Fecal Microbiota Transplantation (FMT) in Multiple Sclerosis
Official title: Single-Arm, Non-Randomized, Time Series, Single-Subject Study: Fecal Microbiota Transplantation (FMT) in Multiple Sclerosis
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Multiple Sclerosis, Relapsing-Remitting
Keywords: FMT
Microbiome
Gait
Longitudinal
Multiple Sclerosis
Lead sponsor: Rush University Medical Center
Sponsor class: OTHER
First posted: 2019-06-05
Enrollment: 1
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
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.

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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Fecal microbial community structure and functional changes over six time frames for phylum, genus and species taxonomic level bacteria, virus, fungi, and archaea.
timeFrame: Baseline, 3 week, 13 week, 26 week, 39 week, 52 week
measure: Walking and balance changes over four time frames for stride time (seconds).
timeFrame: Baseline, 3 week, 13 week, 52 week
measure: Walking and balance changes over four time frames for stride distance (meters).
timeFrame: Baseline, 3 week, 13 week, 52 week
measure: Walking and balance changes over four time frames for cadence (total number of steps per minute).
timeFrame: Baseline, 3 week, 13 week, 52 week
measure: Walking and balance changes over four time frames for step width (meters).
timeFrame: Baseline, 3 week, 13 week, 52 week
measure: Walking and balance changes over four time frames for average pelvis forward velocity (meters per second).
timeFrame: Baseline, 3 week, 13 week, 52 week
measure: Walking and balance changes over four time frames for pelvis smoothness (pelvis horizontal speed).
timeFrame: Baseline, 3 week, 13 week, 52 week
Secondary outcomes:
measure: 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).
timeFrame: Baseline, 3 week, 13 week, 26 week, 39 week, 52 week
measure: Measurement of blood serum biomarker brain-derived neurotrophic factor (BDNF) (ng/ml) changes over six time frames.
timeFrame: Baseline, 3 week, 13 week, 26 week, 39 week, 52 week
measure: Sleep changes over six time frames.
timeFrame: Baseline, 3 week, 13 week, 26 week, 39 week, 52 week
measure: Food timing changes over six time frames.
timeFrame: Baseline, 3 week, 13 week, 26 week, 39 week, 52 week
measure: Gastrointestinal symptoms changes over six time frames (t-scores, mean, standard deviations).
timeFrame: Baseline, 3 week, 13 week, 26 week, 39 week, 52 week
measure: Walking changes over six time frames.
timeFrame: Baseline, 3 week, 13 week, 26 week, 39 week, 52 week
measure: Lesions changes over three time frames.
timeFrame: Baseline, 26 week and 52 week
measure: Food and frequency of consumption changes over six time frames.
timeFrame: Baseline, 3 week, 13 week, 26 week, 39 week, 52 week
measure: Single day food recall changes over six time frames.
timeFrame: Baseline, 3 week, 13 week, 26 week, 39 week, 52 week
measure: Diet changes over six time frames.
timeFrame: Baseline, 3 week, 13 week, 26 week, 39 week, 52 week
measure: Measurement of blood serum biomarker Interleukin-6 (IL-6) (pg/ml) changes over six time frames.
timeFrame: Baseline, 3 week, 13 week, 26 week, 39 week, 52 week
measure: Measurement of blood serum biomarker Interleukin-* (IL-8) (pg/ml) changes over six time frames.
timeFrame: Baseline, 3 week, 13 week, 26 week, 39 week, 52 week
measure: Measurement of blood serum biomarker Tumor necrosis factor alpha (TNFα) (pg/ml) changes over six time frames.
timeFrame: Baseline, 3 week, 13 week, 26 week, 39 week, 52 week
Other outcomes:
Locations:
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
Study officials:
affiliation: Rush University Medical Center
name: Ali Keshavarzian, MD
role: PRINCIPAL_INVESTIGATOR
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