Fecal Microbiota Transplantation for the Treatment of Diarrhea-Predominant Irritable Bowel Syndrome

This is a multicenter study including Montefiore Medical Center, Concorde Medical Group PLLC
and the Medical Research Center of Connecticut/Yale-New Haven Hospital Langone Medical
Center. Patients with IBS-D will be recruited from outpatient gastroenterology clinics at
these institutions and referrals from the medical community.

FMT capsules and placebo capsules, provided by OpenBiome, Medford, MA, will be used for this
study. Patients will be randomized to undergo FMT using fecal capsules (experimental group)
or placebo capsules (control group) via a computer-generated program. All patients will
cross-over into the alternate arm of the study at 12 weeks. Therefore, all patients enrolled
will receive the experimental drug during the course of the study. Each patient will be
enrolled in the study for a total of 6 months.

Intestinal microbiome analyses using DNA sequencing and non-cultivation-based approaches (16S
DNA technology) will be performed in all patients in the experimental and control groups to
assess stability of the microbiome over time.

Inclusion Criteria:

- age 19-65 years

- established diagnosis of IBS-D as determined by Rome III Criteria

- moderate-severe disease activity (as determined by an IBS-Symptom Severity Score ≥175)

- persistent symptoms despite conventional therapy

- normal colonoscopy with biopsies in the past for work-up of IBS symptoms

- negative work-up for celiac disease either by duodenal biopsies or negative serologies

Exclusion Criteria:

- pregnancy

- nursing

- cognitive impairment or severe neuropsychiatric comorbidities who are incapable of
providing their own informed consent

- severely immunocompromised or immunosuppressed patients (e.g., organ transplant
recipients, severe neutropenia with an absolute neutrophil count of <500cells/mL,
current treatment or treatment within 3 months with anti-neoplastic agents and
HIV-positive patients with CD4 counts <200cells/mm^3)

- treated with any antibiotics in the 3 months prior to FMT

- GI symptoms can be explained by the presence of an underlying organic disease
including, underlying inflammatory bowel disease, infectious enteritis, previously
established and untreated small intestinal bacterial overgrowth or known motility
disorder

- previous FMT

- severe (anaphylactic) food allergy

- unable to comply with protocol requirements

- American Society of Anesthesiologists (ASA) Physical Status classification IV and V

- acute illness or fever on the day of planned FMT will be excluded (not randomized)
with the option of including that subject at a future date

- new antidepressant started or dose of antidepressant change <3 months prior to
enrollment

- elevated ESR or CRP within the past 3 months

- baseline laboratory abnormalities on CBC, chemistry or liver tests

- pain score >75 on IBS-SSS