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
|Condition or disease||Intervention/treatment||Phase|
|Multiple Sclerosis||Biological: Fecal microbial transplant (FMT)||Early Phase 1|
The specific aims are to:
- Determine the tolerability of a single dose of 30 capsules in a group of adults with MS
- Determine whether any unexpected outcomes arise in participants who successfully complete an FMT procedure consisting of a single dose of 30 capsules
- Determine whether successfully completed FMT leads to engraftment of donor microbiome in participants
- 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
- Determine whether engrafted species following the FMT, if detected, result in any changes in immune or metabolomic parameters relative to baseline
- 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
- 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 :||Interventional (Clinical Trial)|
|Estimated Enrollment :||15 participants|
|Intervention Model:||Single Group Assignment|
|Intervention Model Description:||Pre/post pilot investigational study|
|Masking:||None (Open Label)|
|Official Title:||A Pilot Study of Oral FMT (Fecal Microbial Transplant) in Subjects With Multiple Sclerosis|
|Actual Study Start Date :||October 28, 2019|
|Estimated Primary Completion Date :||December 30, 2022|
|Estimated Study Completion Date :||December 30, 2022|
Fecal microbial transplant capsules
Biological: Fecal microbial transplant (FMT)
Oral fecal microbial transplant capsules
- 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
- 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)
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04096443
|Contact: Joseph B Guarnaccia, MDfirstname.lastname@example.org|
|Contact: Rockiy G. Ayettey, MS||203 732 1265 ext email@example.com|
|United States, Connecticut|
|Derby, Connecticut, United States, 06418|
|Contact: Joseph B Guarnaccia, MD 203-676-7436 firstname.lastname@example.org|
|Contact: Rockiy G Ayettey, MS 203 732 1265 ext 300 email@example.com|
|Principal Investigator: Joseph B Guarnaccia, MD|
|Sub-Investigator: Frederick Browne, MD|
|Principal Investigator:||Joseph B Guarnaccia, MD||Griffin Hospital|
|Principal Investigator:||Frederick Browne, MD||Griffin Hospital|