Clinical trial NCT04096443: Oral FMT (Fecal Microbial Transplant) in Subjects with Multiple Sclerosis
Official title: A Pilot Study of Oral FMT (Fecal Microbial Transplant) in Subjects with Multiple Sclerosis
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: EARLY_PHASE1
Conditions: Multiple Sclerosis
Keywords: Fecal microbial transplant
FMT
Pilot study
Lead sponsor: Griffin Hospital
Sponsor class: OTHER
Collaborators: name: Yale-Griffin Prevention Research Center
First posted: 2019-09-19
Enrollment: 9
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Pre/post pilot investigational study
Primary purpose: TREATMENT

Brief summary: The goal of this pilot study is to determine whether fecal microbial transplant (FMT) has the potential to be an effective, safe and tolerable therapy for the treatment of multiple sclerosis (MS). The investigators plan to gather preliminary data in a small cohort of 10 to 15 adults with MS.

Detailed description: The specific aims are to:

1. Determine the tolerability of a single dose of 30 capsules in a group of adults with MS
2. Determine whether any unexpected outcomes arise in participants who successfully complete an FMT procedure consisting of a single dose of 30 capsules
3. Determine whether successfully completed FMT leads to engraftment of donor microbiome in participants
4. If the FMT leads to engraftment of donor microbiome in participants, determine whether participants revert back to previous microbiome profiles, and if so, at what time point
5. Determine whether engrafted species following the FMT, if detected, result in any changes in immune or metabolomic parameters relative to baseline
6. Determine whether the FMT has any adverse impact, relative to baseline, on study participants' self-reported levels of fatigue, mental well-being, and health-related qualify of life
7. Determine whether the FMT has any adverse impact, relative to baseline, on study participants' neurological status, relative to baseline

The study population will consist of adults with clinically definite MS who are currently untreated with any disease-modifying therapy or are being treated with glatiramer acetate or interferon beta. The research team will offer study participants a single FMT procedure in the form of 30 oral capsules which contain fecal material. Study participants will visit Griffin Hospital facilities 8 times. The first visit will involve a clinical screening. Of the 7 remaining visits, 6 will involve data collection and one will involve the FMT procedure.

Eligibility criteria: Inclusion Criteria:

1. Diagnosis of clinically definite multiple sclerosis (CDMS) by 2017 McDonald Criteria
2. Ages between 18 and 55 years, inclusive;
3. Expanded Disability Status Score (EDSS) between 1.0 and 6.5.
4. Currently untreated with any disease-modifying therapy (DMT) or currently being treated with glatiramer acetate or interferon beta.
5. Ability to travel to Griffin Hospital for 8 visits over a 5-month period

Exclusion Criteria:

1. Inability to give consent;
2. Non-fluency in English;
3. Inability to adhere to the protocol;
4. Inability (e.g., dysphagia) to or unwillingness to swallow capsules;
5. Active gastrointestinal infection at the time of enrollment;
6. Use of antibiotics or corticosteroids within three months of study entry;
7. Requiring or anticipating antibiotic use during the four weeks after study entry;
8. MS relapse within one month of study entry;
9. Previous use of any of the following FDA-approved disease-modifying drugs within 12 months of study entry, including natalizumab, fingolimod, siponimod, ozanimod, teriflunomide, diroximel, ocrelizumab, ofatumumab, and/or dimethyl fumarate; or any of the following off-label therapies, including rituximab and cyclophosphamide;
10. Any previous use of the following FDA-approved DMTs, including mitoxantrone, alemtuzumab, and cladribine;
11. IV immunoglobulin or plasma exchange within six months prior to study entry;
12. Known or suspected toxic megacolon and/or known small bowel ileus;
13. Major gastrointestinal surgery (e.g., significant bowel resection) within 3 months prior to enrollment (this does not include appendectomy or cholecystectomy);
14. History of total colectomy or bariatric surgery;
15. Concurrent intensive induction chemotherapy, radiation therapy or biological treatment for active malignancy;
16. Anticipated life expectancy of less than six months;
17. Concomitant other known autoimmune diseases;
18. Concomitant pulmonary, cardiac, gastrointestinal (except as noted above) (Crohns, Colitis, inflammatory bowel, intestinal blockage), hepatic, dermatological or genitourinary disease.
19. Moderate to severe dysphagia;
20. History of alcohol abuse, as defined by the following criteria:

    Men: 5 or more alcoholic beverages per session or day, or 15 or more per week; Women: 4 or more alcoholic beverages per session or day, or 8 or more per week;
21. History of illicit drug abuse, e.g., of cocaine, heroin, PCP, and/or narcotic substances;
22. Grade 1 or greater lymphopenia, as measured at baseline/clinical screening;
23. Liver Function Tests (LFTs) greater than 1½ times upper limits of normal, as measured at baseline/clinical screening;
24. History of use of FMT or microbiome-based products (excluding probiotics) at any time, excluding this study;
25. History of severe anaphylactic or anaphylactoid food allergy;
26. History of solid organ transplantation;
27. Risk for Cytomegalovirus (CMV) or Epstein Barr virus (EBV) associated disease (at investigator's discretion, e.g., immunocompromised and negative (immunoglobulin gamma) IgG testing for CMV or EBV);
28. Women who are pregnant, lactating, planning to become pregnant, and/or not using an effective method of contraception (women of childbearing potential will undergo a pregnancy test, and will be excluded from the study if results are positive);
29. Any allergies to neomycin or similar antibiotics such as amikacin (Amikin), gentamicin (Garamycin), kanamycin (Kantrex), paromomycin (Humatin, Paromycin), streptomycin, or tobramycin (Nebcin, Tobi);
30. Any condition that would jeopardize the safety or rights of the subject, would make it unlikely for the subject to complete the study, or would confound the study results.
31. Household contacts, including children under the age of 5 years, pregnant women, any person with an immunocompromised condition or on medications causing immunosuppression or persons 70 years or older;
32. Failure to document a COVID-19 vaccine series at least two weeks prior to study entry.

Primary outcomes:
measure: Change in engraftment of donor microbiome in stool samples
timeFrame: Pre-FMT and 4 time points post-FMT (3-7 days, 10-15 days, 40-45 days, 100-110 days)
Secondary outcomes:
measure: Change in immune markers in blood samples assessed using assays of lymphocyte phenotyping and intracellular cytokines
timeFrame: Pre-FMT and 2 time points post-FMT (40-45 days, 100-110 days)
measure: Change in neurological status using Kurtzke Functional Systems Scale (FSS)
timeFrame: Pre-FMT and 4 time points post-FMT (3-7 days, 10-15 days, 40-45 days, 100-110 days)
measure: Change in neurological status using Kurtzke Expanded Disability Status Scale (EDSS)
timeFrame: Pre-FMT and 4 time points post-FMT (3-7 days, 10-15 days, 40-45 days, 100-110 days)
measure: Change in self-reported health-related quality of life assessed using the Health Status Questionnaire Short-Form 36 (SF-36)
timeFrame: Pre-FMT and 3 time points post-FMT (10-15 days, 40-45 days, 100-110 days)
measure: Change in self-reported mental health status assessed using Mental Health Inventory (MHI)
timeFrame: Pre-FMT and 3 time points post-FMT (10-15 days, 40-45 days, 100-110 days)
measure: Change in self-reported levels of fatigue assessed using Modified Fatigue Impact Scale (MFIS)
timeFrame: Pre-FMT and 3 time points post-FMT (10-15 days, 40-45 days, 100-110 days)
measure: Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
timeFrame: Day of FMT procedure and 5 time points post-FMT (1 day, 3-7 days, 10-15 days, 40-45 days, 100-110 days), or any time the study team is contacted by subjects who report adverse side effects
Other outcomes:
Locations:
city: Derby
country: United States
facility: Griffin Hospital
state: Connecticut
Study officials:
affiliation: Griffin Hospital
name: Joseph B Guarnaccia, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Griffin Hospital
name: Frederick Browne, MD
role: PRINCIPAL_INVESTIGATOR
References: