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

Montefiore Medical Center48 enrolled

Overview

The objectives of this study are (1) to determine the efficacy of fecal microbiota transplantation (FMT), given as oral capsules, compared with placebo for the treatment of refractory diarrhea-predominant irritable bowel syndrome (IBS-D); (2) determine the impact of FMT on the intestinal microbiome of patients with IBS-D; and (3) assess the safety, feasibility, and tolerability of FMT for patients with IBS-D.

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Conditions

Irritable Bowel Syndrome

Interventions

Fecal microbiota transplantation capsulesDRUG

Fecal microbiota transplantation capsules contain extensively screened donor stool and are prepared by OpenBiome, Medford, MA.

Placebo capsulesDRUG

Placebo capsules prepared by OpenBiome, Medford, MA

Eligibility

Sex: ALLMin age: 19 YearsMax age: 65 Years

Medical Language ↔ Plain English

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

Locations (3)

Medical Research Center of Connecticut

Hamden, Connecticut, United States

Concorde Medical Group

New York, New York, United States

Montefiore Medical Center

The Bronx, New York, United States

Outcomes

Primary Outcomes

Within and Between Group Comparisons of Disease Severity as Determined by Irritable Bowel Syndrome-Symptom Severity Score (IBS-SSS)

Within and between group comparisons of changes (from baseline) in Irritable Bowel Syndrome-Symptom Severity Score (IBS-SSS), obtained via administration of a Questionnaire, for each of the two arms/groups (FMT capsules first, and placebo capsules first). The scale range was 0-500 (min-max). Scores were averaged among time points to yield an overall mean score. Higher scores were indicative of greater disease severity (worse outcome). Subjects were categorized as having mild (75-175), moderate (175-300), or severe (\>300) irritable bowel syndrome (IBS) based on symptomology. Only the following time points were analyzed: Baseline vs Week 12 and Week 24.

Time frame: Baseline, Week 12 (before cross-over), Week 24

Secondary Outcomes

Within and Between Group Comparisons of Quality of Life as Determined by the Irritable Bowel Syndrome-Quality of Life (IBS-QOL) Score

Within and between group comparisons of changes (from baseline) in Irritable Bowel Syndrome-Quality of Life (IBS-QOL), obtained via administration of a Questionnaire, for each of the two arms/groups (FMT capsules first, and placebo capsules first). Irritable Bowel Syndrome-Quality of Life (IBS-QOL) is administered via a questionnaire of 34 items each with an individual five-point response scale. The responses to these items are summed and averaged for a total score and then transformed to a 100-point scale for ease of interpretation based on a validated method. IBS-QOL is measured on a scale range of 0-100. Higher IBS-QOL scores are indicative of a better IBS-specific quality of life. Only the following time points were analyzed: Baseline vs Week 12

Time frame: Baseline, Week 12 (before cross-over), Week 24

Intestinal Microbiota Composition Pre- and Post-FMT (Fecal Microbiota Transplantation)

Microbiota composition before and after FMT were assessed among FMT responders and FMT non-responders. Only patients who received FMT capsules at the start of this clinical trial were included. Placebo capsule recipients were not included in these analyses. Data were analyzed up to 12 weeks and not beyond. Microbiome data following cross-over were not analyzed because of the potential for carry-over and order effects in the second half of the trial. Outcomes assessed included alpha and beta diversity (Jensen-Shannon divergence) and abundance of Bacteroidetes, Firmicutes and Prevotella. All of the microbiome data that were analyzed are included in the table below. No additional microbiome data from this clinical trial were analyzed.

Data from ClinicalTrials.gov

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Time frame: Baseline, Week 1, Week 4 and Week 12

Anxiety as Measured by the Hospital Anxiety and Depression Scale (HADS). HADS-A (Anxiety)

Anxiety at baseline and at the time of cross-over (Week 12) as measured by Hospital Anxiety and Depression Scale (HADS). HADS-A (Anxiety) The Hospital Anxiety and Depression Scale (HADS) is a fourteen item scale which was administered via questionnaire. Seven of the items relate to anxiety (HADS-A) and seven relate to depression (HADS-D). Each item on the questionnaire is scored from 0-3 and this means that a person can score between 0 and 21 for either anxiety or depression. The HADS uses a scale and therefore the data returned from the HADS is ordinal. Higher HADS scores are indicative of more severe depression and anxiety. Only the following time points were analyzed: Baseline vs Week 12

Time frame: Baseline, Week 12 (before cross-over), Week 24

Depression as Measured by the Hospital Anxiety and Depression Scale (HADS). HADS-D (Depression)

Depression at baseline and at the time of cross-over (Week 12) as measured by Hospital Anxiety and Depression Scale (HADS). HADS-D (Depression) The Hospital Anxiety and Depression Scale (HADS) is a fourteen item scale which was administered via questionnaire. Seven of the items relate to anxiety (HADS-A) and seven relate to depression (HADS-D). Each item on the questionnaire is scored from 0-3 and this means that a person can score between 0 and 21 for either anxiety or depression. The HADS uses a scale and therefore the data returned from the HADS is ordinal. Higher HADS scores are indicative of more severe depression and anxiety. Only the following time points were analyzed: Baseline vs Week 12

Time frame: Baseline, Week 12 (before cross-over), Week 24

Bowel Consistency as Measured by the Bristol Stool Form Scale (BSFS)

Bowel consistency as measured by the Bristol Stool Form Scale on a daily basis. The Bristol Stool Form Scale was administered via questionnaire. This scale is a diagnostic medical tool designed to classify the form of human feces into seven categories. Assigned categories range from 1-7 based on appearance of the stool. Type 1 and 2 stools indicate constipation. Type 4 are the ideal stools as they are easy to defecate while not containing excess liquid, Type 5 tends towards diarrhea, and Types 6 and 7 indicate diarrhea. Only the following time points were analyzed: Baseline vs Week 12

Time frame: Baseline, Week 12 (before cross-over), Week 24

Number of Participants With Adverse Events as a Measure of Safety and Tolerability

The total number of participants in each of the arms/groups (FMT and Placebo) who experienced at least one adverse event (AE) as recorded in patient diaries.

Time frame: All AEs over 24 weeks

Satisfaction With Fecal Microbiota Transplantation (FMT)

Weekly assessments of satisfaction with the Fecal Microbiota Transplantation (FMT) will be recorded in patient diaries.