Fecal Microbial Transplant (FMT) for Sjogrens Syndrome

• ClinicalTrials.gov Identifier: NCT03926286
• Recruitment Status: Completed
• First Posted: April 24, 2019
• Last Update Posted: June 5, 2020
• Sponsor: University of Miami
• Collaborators: Sjogrens Syndrome Foundation; Microbiome Health Research Institute
• Information provided by (Responsible Party): Anat Galor, University of Miami

Study Description

Brief Summary:

This is an open label study to evaluate the effect of Fecal Microbiota Transplantation (FMT) on the gut microbiome and Systemic parameters.

Condition or disease	Intervention/treatment	Phase
Sjogren's Syndrome	Drug: FMP-30	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 10 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Fecal Microbial Transplant for Sjogrens Syndrome
• Actual Study Start Date: April 15, 2019
• Actual Primary Completion Date: June 1, 2020
• Actual Study Completion Date: June 1, 2020

Arms and Interventions

Arm	Intervention/treatment
Experimental: FMT for Sjogrens; FMT- active ingredient coming from participant's screening stool	Drug: FMP-30; FMP-30 containing frozen human fecal microbiota administered as (3) units of FMP30 enema on Day 0 and Week1

Outcome Measures

Primary Outcome Measures :

1. Number of participants with reported adverse events (AEs) and serious adverse events (SAEs) [ Time Frame: 7 months ]
   As an evaluation of the safety of FMT, the number of participants with reported AEs and SAEs will be collected. All occurrences of AEs and SAEs, regardless of relatedness to FMT, will be reported and assessed by the clinician using the NIH CTCAE.
2. Number of participants with stable microbiome engraftment [ Time Frame: month 3 ]
   Engraftment will be analyzed via the Jensen-Shannon divergence (JSD). The engraftment scores will be the ratio between the donors and recipients at the bacterial genus level. Participants who successfully engraft will more closely resemble the donor microbial profile on JSD analysis.

Secondary Outcome Measures :

1. Change in dry eye symptoms [ Time Frame: baseline, 1 week, 1 month, 3 months ]
   Dry eye symptoms will be measured by the Ocular Surface Disease Index (OSDI) Scale 0-100 Continuous with higher scores representing greater dry eye symptoms
2. Change in dry eye symptoms [ Time Frame: baseline, 1 week, 1 month, 3 months ]
   Dry eye symptoms will be measured by the Dry Eye Questionnaire 5 (DEQ5) Scale Range 0-22 Continuous with a higher number representing greater symptomatology of dry eye
3. Change in diversity of bacterial communities [ Time Frame: Pre FMT, 3 months post FMT ]
   This will be captured via high-throughput 16S gene sequencing using DNA extracted from stool specimens in study participants. The Shannon diversity index will be used as our primary measure of diversity.
4. Change in system immune profiles as measured by T cell populations [ Time Frame: Pre-FMT, 1 Week, 1 Month, 3 months post FMT ]
   System immune profiles will be evaluated by completing a comprehensive immuno-phenotypic profile from blood samples evaluating T cell populations including Th1, Th17, and T regulatory cells.
5. Change in ocular and systemic symptoms as measured by the quality of life SF-12 Questionnaire [ Time Frame: Pre-FMT, 1 Week, 1 Month, 3 months post FMT ]
   Ranges 0-100 with higher scores representing a better quality of life
6. Change in self-reported ocular pain as assessed by the Numerical Rating Scale(NRS) [ Time Frame: Pre-FMT, 1 Week, 1 Month, 3 months post FMT ]
   NRS Scoring Ranges from 0-10 with 0=no pain sensation and 10=the most intense eye pain imaginable
7. Change in self-reported ocular pain as assessed by the Short-form McGill Pain Questionnaire(SFM-PQ) [ Time Frame: Pre-FMT, 1 Week, 1 Month, 3 months post FMT ]
   SFM-PQ Scoring Ranges from 0-45 with zero to 45 with a higher score indicating more server eye pain
8. Change in self-reported ocular pain as assessed by the Neuropathic Pain Symptom Inventory (NPSI) [ Time Frame: Pre-FMT, 1 Week, 1 Month, 3 months post FMT ]
   NPSI Scoring Ranges from 0-100 with the higher score indicating the worse pain imaginable.
9. Depression as assessed by the Patient Health Questionnaire-9 (PHQ-9) [ Time Frame: Pre-FMT, 1 Week, 1 Month, 3 months post FMT ]
   PHQ-9 scoring Ranges from 0-27 with the higher score indicating a greater degree of depression
10. Depression as assessed by the Symptom Checklist 90 for Depression (SCL-90 Depression) [ Time Frame: Pre-FMT, 1 Week, 1 Month, 3 months post FMT ]
    SCL-90 Depression scoring ranges from 0-4 with the higher score indicating a greater degree of depression.
11. Anxiety as assessed by the Symptom Checklist 90 for Anxiety (SCL-90 Anxiety) [ Time Frame: Pre-FMT, 1 Week, 1 Month, 3 months post FMT ]
    SCL-90 Anxiety scoring ranges from 0-4 with the higher score indicating a greater degree of anxiety.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion criteria:

1. Positive diagnosis of Sjogrens syndrome, defined by meeting two or more of the following three criteria:

   • Positive serum anti-SS-A/Ro and/or anti-SS-B/La (or positive rheumatoid factor and ANA ≥ 1:320)
   • Labial salivary gland biopsy exhibiting focal lymphocytic sialadenitis with a focus score ≥ focus/4 mm2
   • Keratoconjunctivitis sicca with ocular staining score ≥ 3 (assuming that individual is not currently using daily eye drops for glaucoma, and has not had corneal surgery or cosmetic eyelid surgery in the last 5 years)

   Or by both of the following:

   Positive antibodies to one of the early markers of Sjogrens Syndrome:

   • Anti-salivary gland protein 1 (SP1)
   • Anti-carbonic anhydrase 6 (CA6)
   • Parotid secretory protein (PSP) Ocular staining score ≥ 3
2. Age ≥ 18 years at time of enrollment
3. Able to provide signed and dated informed consent
4. Women of child childbearing potential in sexual relationships with men must use an acceptable method of contraception§ from 30 days prior to enrollment until 4 weeks after completing study treatment.

5. Males must agree to avoid impregnation of women during and for four weeks after completing study treatment through use of an acceptable method of contraception*.

   • Includes, but is not limited to, barrier with additional spermicidal foam or jelly, intrauterine device, hormonal contraception (started at least 30 days prior to study enrollment), intercourse with men who underwent vasectomy.

     • Includes, but is not limited to, barrier with additional spermicidal foam or jelly and vasectomy.

Participant exclusion criteria

Exclusion Criteria:

1. Inability to provide informed consent and/or unable or unwilling to comply with protocol requirements.
2. Antibiotics for at least 2 weeks prior to FMT.
3. Active infection for >15 days: bacteremia, urinary tract infection, pneumonia or abdominal collection.
4. Known or suspected toxic megacolon and/or known small bowel ileus.
5. Previous FMT
6. Major gastrointestinal surgery (e.g. significant bowel resection) within 3 months before enrollment. This does not include appendectomy or cholecystectomy.
7. History of total colectomy or bariatric surgery.
8. Antibiotics for the treatment of an active infection or anticipated antibiotic use during trial duration.
9. Concurrent intensive induction chemotherapy, radiation therapy or biological treatment for active malignancy.
10. Expected life expectancy < 6 months
11. Patients with a history of severe anaphylactic or anaphylactoid food allergy.
12. Solid organ transplant patients ≤ 90 days post-transplant or on active treatment for rejection.
13. Neutropenia (<500 neutrophils/mL) or other severe immunosuppression. Patients on monoclonal antibodies to B and T cells, anti-tumor necrosis factor, glucocorticoids, antimetabolites, calcineurin inhibitors may be enrolled after consultation with their medical doctor.
14. Renal failure (GFR <30 or dialysis)
15. Human immunodeficiency virus+ controlled or not well controlled on antiretroviral therapy
16. Regular probiotic supplement use within prior 2 weeks to enrollment
17. Pregnancy or inability/unwillingness to use contraceptives.
18. A 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 results of the study.
19. Exclusion on the discretion of the PI.

Contacts and Locations

Locations

United States, Florida

University of Miami

Miami, Florida, United States, 33133

Sponsors and Collaborators

University of Miami

Sjogrens Syndrome Foundation

Microbiome Health Research Institute

Investigators

• Principal Investigator: Anat Galor, MD, MSPH; University of Miami

More Information

Publications:

Zaheer M, Wang C, Bian F, Yu Z, Hernandez H, de Souza RG, Simmons KT, Schady D, Swennes AG, Pflugfelder SC, Britton RA, de Paiva CS. Protective role of commensal bacteria in Sjogren Syndrome. J Autoimmun. 2018 Sep;93:45-56. doi: 10.1016/j.jaut.2018.06.004. Epub 2018 Jun 20.

De Luca F, Shoenfeld Y. The microbiome in autoimmune diseases. Clin Exp Immunol. 2019 Jan;195(1):74-85. doi: 10.1111/cei.13158.

Wang C, Zaheer M, Bian F, Quach D, Swennes AG, Britton RA, Pflugfelder SC, de Paiva CS. Sjogren-Like Lacrimal Keratoconjunctivitis in Germ-Free Mice. Int J Mol Sci. 2018 Feb 13;19(2):565. doi: 10.3390/ijms19020565.

de Paiva CS, Jones DB, Stern ME, Bian F, Moore QL, Corbiere S, Streckfus CF, Hutchinson DS, Ajami NJ, Petrosino JF, Pflugfelder SC. Altered Mucosal Microbiome Diversity and Disease Severity in Sjogren Syndrome. Sci Rep. 2016 Apr 18;6:23561. doi: 10.1038/srep23561.

• Responsible Party: Anat Galor, Associate Professor, University of Miami
• ClinicalTrials.gov Identifier: NCT03926286
• Other Study ID Numbers: 20170733
• First Posted: April 24, 2019
• Last Update Posted: June 5, 2020
• Last Verified: June 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Anat Galor, University of Miami:

Dry Eye; Auto-Immune Disorder

Additional relevant MeSH terms:

Sjogren's Syndrome; Syndrome; Dry Eye Syndromes; Disease; Pathologic Processes; Arthritis, Rheumatoid; Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Xerostomia; Salivary Gland Diseases; Mouth Diseases; Stomatognathic Diseases; Lacrimal Apparatus Diseases; Eye Diseases; Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases