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Oral FMT (Fecal Microbial Transplant) in Subjects With Multiple Sclerosis

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ClinicalTrials.gov Identifier: NCT04096443
Recruitment Status : Recruiting
First Posted : September 19, 2019
Last Update Posted : February 7, 2022
Sponsor:
Collaborators:
Yale-Griffin Prevention Research Center
Multiple Sclerosis Treatment Center, Derby, Connecticut
Information provided by (Responsible Party):
Griffin Hospital

Tracking Information
First Submitted Date  ICMJE August 7, 2019
First Posted Date  ICMJE September 19, 2019
Last Update Posted Date February 7, 2022
Actual Study Start Date  ICMJE October 28, 2019
Estimated Primary Completion Date December 30, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 18, 2019)
Change in engraftment of donor microbiome in stool samples [ Time Frame: Pre-FMT and 4 time points post-FMT (3-7 days, 10-15 days, 40-45 days, 100-110 days) ]
Evidence of engraftment as measured by 16s rRNA microbiome sequencing
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 23, 2022)
  • Change in immune markers in blood samples assessed using assays of lymphocyte phenotyping and intracellular cytokines [ Time Frame: Pre-FMT and 2 time points post-FMT (40-45 days, 100-110 days) ]
    Phenotyping will be performed: for T cells - TCRβ, TCRγ, CD4, CD8, CD25, CD44, CD62L, CD69, PD1, CTLA4; for B cells - B220, CD19, CD21, CD23, CD1d, CD5, IgA, IgG1, IgG2a(c), IgG2b; for DCs - CD11c, CD11b, BDCA1, CD8, CD103, CD205 and CD86. The intracellular cytokine (ICC) panel will be IL-6, IL-10, IL-12, IL-17, TNFα, and IFNγ.
  • Change in neurological status using Kurtzke Functional Systems Scale (FSS) [ Time Frame: Pre-FMT and 4 time points post-FMT (3-7 days, 10-15 days, 40-45 days, 100-110 days) ]
    The FSS uses a set of single-item ordinal clinical rating scales to rate levels of function in seven domains (pyramidal, cerebellar, brainstem, sensory, bowel and bladder, visual, and cerebral/mental). Each single item scale ranges from 0 to 5 or 6 (0 = "normal;" 5 or 6 represents the worst level of function; and 9 = "unknown"). For each single item scale, scores representing the highest level of function are as follows: pyramidal: 6 = "quadriplegia"; cerebellar: 5 = "unable to perform coordinated movements due to ataxia"; brainstem: 5 = "inability to swallow or speak"; sensory: 6 = "sensation essentially lost below the head"; bowel and bladder: 6 = loss of bowel and bladder function"; visual: 6 = "grade 5 plus maximal visual acuity of better eye of 20/60 or less"; cerebral/mental: 5 = "dementia or chronic brain syndrome - severe or incompetent." The ratings are used in conjunction with observations and information concerning gait and use of assistive devices to rate the EDSS.
  • Change in neurological status using Kurtzke Expanded Disability Status Scale (EDSS) [ Time Frame: Pre-FMT and 4 time points post-FMT (3-7 days, 10-15 days, 40-45 days, 100-110 days) ]
    The EDSS is an ordinal clinical rating scale ranging from 0 (normal neurological examination) to 10 (death due to MS) in half-point increments.
  • Change in self-reported health-related quality of life assessed using the Health Status Questionnaire Short-Form 36 (SF-36) [ Time Frame: Pre-FMT and 3 time points post-FMT (10-15 days, 40-45 days, 100-110 days) ]
    The SF-35 has 36 questions. It has a single item covering change in health status over the last year and 8 multi-item scales. The scoring system is relatively complex and generates 8 subscales and 2 summary scores. The 8 subscales are: physical functioning, role limitations due to physical problems, bodily pain, general health perceptions, vitality, social functioning, role-limitations due to emotional problems, and mental health. Two summary scales (Physical and Mental) have been derived using factor analytic methods. Scales are set up so that a higher score indicates better health. To achieve this, responses on 10 items are recoded before being added to other items on the same scale. Raw scale scores are then transformed to a 0-100 scale.
  • Change in self-reported mental health status assessed using Mental Health Inventory (MHI) [ Time Frame: Pre-FMT and 3 time points post-FMT (10-15 days, 40-45 days, 100-110 days) ]
    The MHI consists of 18 items and assesses several domains of mental health. The scoring system generates 4 subscale scores (Anxiety, Depression, Behavioral Control, and Positive Affect) and 1 total score. The subscale and total scores range from 0-100, with higher scores indicating better mental health.
  • Change in self-reported levels of fatigue assessed using Modified Fatigue Impact Scale (MFIS) [ Time Frame: Pre-FMT and 3 time points post-FMT (10-15 days, 40-45 days, 100-110 days) ]
    The MFIS provides an assessment of the effects of fatigue on physical, cognitive, and psychosocial function. It consists of 21 items. The items be aggregated into 3 subscales (Physical, Cognitive, and Psychosocial), as well as into a total MFIS score. All items are scaled so that higher scores indicate a greater impact of fatigue on a patient's activities. The physical subscale can range from 0-36. The cognitive subscale can range from 0-40. The psychosocialsub scale can range from 0-8. The Total MFIS score can range from 0-84.
  • Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] [ Time Frame: 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 ]
    Measured by subject's ability to consume capsules as directed without vomiting or adverse side effects (as opposed to mild side effects)
Original Secondary Outcome Measures  ICMJE
 (submitted: September 18, 2019)
  • Change in immune markers in blood samples assessed using assays of lymphocyte phenotyping and intracellular cytokines [ Time Frame: Pre-FMT and 2 time points post-FMT (40-45 days, 100-110 days) ]
    Phenotyping will be performed: for T cells - TCRβ, TCRγ, CD4, CD8, CD25, CD44, CD62L, CD69, PD1, CTLA4; for B cells - B220, CD19, CD21, CD23, CD1d, CD5, IgA, IgG1, IgG2a(c), IgG2b; for DCs - CD11c, CD11b, BDCA1, CD8, CD103, CD205 and CD86. The intracellular cytokine (ICC) panel will be IL-6, IL-10, IL-12, IL-17, TNFα, and IFNγ.
  • Change in neurological status using Kurtzke Functional Systems Scale (FSS) [ Time Frame: Pre-FMT and 4 time points post-FMT (3-7 days, 10-15 days, 40-45 days, 100-110 days) ]
    The FSS uses a set of single-item ordinal clinical rating scales to rate levels of function in seven domains (pyramidal, cerebellar, brainstem, sensory, bowel and bladder, visual, and cerebral/mental). Each single item scale ranges from 0 to 5 or 6 (0 = "normal;" 5 or 6 represents the worst level of function; and 9 = "unknown"). For each single item scale, scores representing the highest level of function are as follows: pyramidal: 6 = "quadriplegia"; cerebellar: 5 = "unable to perform coordinated movements due to ataxia"; brainstem: 5 = "inability to swallow or speak"; sensory: 6 = "sensation essentially lost below the head"; bowel and bladder: 6 = loss of bowel and bladder function"; visual: 6 = "grade 5 plus maximal visual acuity of better eye of 20/60 or less"; cerebral/mental: 5 = "dementia or chronic brain syndrome - severe or incompetent." The ratings are used in conjunction with observations and information concerning gait and use of assistive devices to rate the EDSS.
  • Change in neurological status using Kurtzke Expanded Disability Status Scale (EDSS) [ Time Frame: Pre-FMT and 4 time points post-FMT (3-7 days, 10-15 days, 40-45 days, 100-110 days) ]
    The EDSS is an ordinal clinical rating scale ranging from 0 (normal neurological examination) to 10 (death due to MS) in half-point increments.
  • Change in self-reported health-related quality of life assessed using the Health Status Questionnaire Short-Form 36 (SF-36) [ Time Frame: Pre-FMT and 3 time points post-FMT (10-15 days, 40-45 days, 100-110 days) ]
    The SF-35 has 36 questions. It has a single item covering change in health status over the last year and 8 multi-item scales. The scoring system is relatively complex and generates 8 subscales and 2 summary scores. The 8 subscales are: physical functioning, role limitations due to physical problems, bodily pain, general health perceptions, vitality, social functioning, role-limitations due to emotional problems, and mental health. Two summary scales (Physical and Mental) have been derived using factor analytic methods. Scales are set up so that a higher score indicates better health. To achieve this, responses on 10 items are recoded before being added to other items on the same scale. Raw scale scores are then transformed to a 0-100 scale.
  • Change in self-reported mental health status assessed using Mental Health Inventory (MHI) [ Time Frame: Pre-FMT and 3 time points post-FMT (10-15 days, 40-45 days, 100-110 days) ]
    The MHI consists of 18 items and assesses several domains of mental health. The scoring system generates 4 subscale scores (Anxiety, Depression, Behavioral Control, and Positive Affect) and 1 total score. The subscale and total scores range from 0-100, with higher scores indicating better mental health.
  • Change in self-reported levels of fatigue assessed using Modified Fatigue Impact Scale (MFIS) [ Time Frame: Pre-FMT and 3 time points post-FMT (10-15 days, 40-45 days, 100-110 days) ]
    The MFIS provides an assessment of the effects of fatigue on physical, cognitive, and psychosocial function. It consists of 21 items. The items be aggregated into 3 subscales (Physical, Cognitive, and Psychosocial), as well as into a total MFIS score. All items are scaled so that higher scores indicate a greater impact of fatigue on a patient's activities. The physical subscale can range from 0-36. The cognitive subscale can range from 0-40. The psychosocialsub scale can range from 0-8. The Total MFIS score can range from 0-84.
  • Tolerability of FMT capsules measured by ability to consume capsules without vomiting or adverse side effects [ Time Frame: 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 ]
    Measured by subject's ability to consume capsules as directed without vomiting or adverse side effects (as opposed to mild side effects)
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Oral FMT (Fecal Microbial Transplant) in Subjects With Multiple Sclerosis
Official Title  ICMJE A Pilot Study of Oral FMT (Fecal Microbial Transplant) in Subjects With Multiple Sclerosis
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Early Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description:
Pre/post pilot investigational study
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Multiple Sclerosis
Intervention  ICMJE Biological: Fecal microbial transplant (FMT)
Oral fecal microbial transplant capsules
Study Arms  ICMJE Experimental: Intervention
Fecal microbial transplant capsules
Intervention: Biological: Fecal microbial transplant (FMT)
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: September 18, 2019)
15
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 30, 2022
Estimated Primary Completion Date December 30, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Diagnosis of clinically definite multiple sclerosis (CDMS) by 2017 McDonald Criteria
  2. Ages between 18 and 40 years, inclusive;
  3. Expanded Disability Status Score (EDSS) between 1.0 and 5.5.
  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, teriflunomide, and/or dimethyl fumarate;
  10. Any previous use of the following FDA-approved DMTs, including mitoxantrone, alemtuzumab, ocrelizumab, or any of the following off-label therapies, including rituximab and cyclophosphamide;
  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. Marijuana use within the past six months prior to study enrollment, whether for medical reasons or recreational purposes;
  23. History of using tobacco products within the past year prior to study enrollment;
  24. Grade 1 or greater lymphopenia, as measured at baseline/clinical screening;
  25. Liver Function Tests (LFTs) greater than 1½ times upper limits of normal, as measured at baseline/clinical screening;
  26. History of use of FMT or microbiome-based products (excluding probiotics) at any time, excluding this study;
  27. History of severe anaphylactic or anaphylactoid food allergy;
  28. History of solid organ transplantation;
  29. 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);
  30. 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);
  31. Any allergies to neomycin or similar antibiotics such as amikacin (Amikin), gentamicin (Garamycin), kanamycin (Kantrex), paromomycin (Humatin, Paromycin), streptomycin, or tobramycin (Nebcin, Tobi);
  32. 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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 40 Years   (Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Joseph B Guarnaccia, MD 203-732-1290 mstreatmentcenters@griffinhealth.org
Contact: Rockiy G. Ayettey, MS 203 732 1265 ext 300 rockiy.ayettey@yalegriffinprc.org
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04096443
Other Study ID Numbers  ICMJE 2018-09
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Current Responsible Party Griffin Hospital
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Griffin Hospital
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE
  • Yale-Griffin Prevention Research Center
  • Multiple Sclerosis Treatment Center, Derby, Connecticut
Investigators  ICMJE
Principal Investigator: Joseph B Guarnaccia, MD Griffin Hospital
Principal Investigator: Frederick Browne, MD Griffin Hospital
PRS Account Griffin Hospital
Verification Date January 2022

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP