Clinical trial NCT03926286: Fecal Microbial Transplant (FMT) for Sjogrens Syndrome
Official title: Fecal Microbial Transplant for Sjogrens Syndrome
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Sjogren's Syndrome
Keywords: Dry Eye
Auto-Immune Disorder
Lead sponsor: University of Miami
Sponsor class: OTHER
Collaborators: name: Sjogrens Syndrome Foundation
name: Microbiome Health Research Institute
First posted: 2019-04-24
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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


Eligibility 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.

Primary outcomes:
measure: Number of participants with reported adverse events (AEs) and serious adverse events (SAEs)
timeFrame: 7 months
measure: Number of participants with stable microbiome engraftment
timeFrame: month 3
Secondary outcomes:
measure: Change in dry eye symptoms
timeFrame: baseline, 1 week, 1 month, 3 months
measure: Change in dry eye symptoms
timeFrame: baseline, 1 week, 1 month, 3 months
measure: Change in diversity of bacterial communities
timeFrame: Pre FMT, 3 months post FMT
measure: Change in system immune profiles as measured by T cell populations
timeFrame: Pre-FMT, 1 Week, 1 Month, 3 months post FMT
measure: Change in ocular and systemic symptoms as measured by the quality of life SF-12 Questionnaire
timeFrame: Pre-FMT, 1 Week, 1 Month, 3 months post FMT
measure: Change in self-reported ocular pain as assessed by the Numerical Rating Scale(NRS)
timeFrame: Pre-FMT, 1 Week, 1 Month, 3 months post FMT
measure: Change in self-reported ocular pain as assessed by the Short-form McGill Pain Questionnaire(SFM-PQ)
timeFrame: Pre-FMT, 1 Week, 1 Month, 3 months post FMT
measure: Change in self-reported ocular pain as assessed by the Neuropathic Pain Symptom Inventory (NPSI)
timeFrame: Pre-FMT, 1 Week, 1 Month, 3 months post FMT
measure: Depression as assessed by the Patient Health Questionnaire-9 (PHQ-9)
timeFrame: Pre-FMT, 1 Week, 1 Month, 3 months post FMT
measure: Depression as assessed by the Symptom Checklist 90 for Depression (SCL-90 Depression)
timeFrame: Pre-FMT, 1 Week, 1 Month, 3 months post FMT
measure: Anxiety as assessed by the Symptom Checklist 90 for Anxiety (SCL-90 Anxiety)
timeFrame: Pre-FMT, 1 Week, 1 Month, 3 months post FMT
Other outcomes:
Locations:
city: Miami
country: United States
facility: University of Miami
state: Florida
Study officials:
affiliation: University of Miami
name: Anat Galor, MD, MSPH
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: De Luca F, Shoenfeld Y. The microbiome in autoimmune diseases. Clin Exp Immunol. 2019 Jan;195(1):74-85. doi: 10.1111/cei.13158.
citation: 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.
citation: 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.