Clinical trial NCT02328547: Fecal Microbiota Transplantation for the Treatment of Diarrhea-Predominant Irritable Bowel Syndrome
Official title: Randomized, Double-blinded, Placebo-controlled Trial of Fecal Microbiota Transplantation (FMT) for Diarrhea-Predominant Irritable Bowel Syndrome (IBS-D)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Irritable Bowel Syndrome
Keywords: fecal microbiota transplantation
diarrhea-predominant
Lead sponsor: Montefiore Medical Center
Sponsor class: OTHER
First posted: 2014-12-31
Enrollment: 48
Sex: ALL
Minimum age (years): 19
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Within and Between Group Comparisons of Disease Severity as Determined by Irritable Bowel Syndrome-Symptom Severity Score (IBS-SSS)
timeFrame: Baseline, Week 12 (before cross-over), Week 24
Secondary outcomes:
measure: Within and Between Group Comparisons of Quality of Life as Determined by the Irritable Bowel Syndrome-Quality of Life (IBS-QOL) Score
timeFrame: Baseline, Week 12 (before cross-over), Week 24
measure: Intestinal Microbiota Composition Pre- and Post-FMT (Fecal Microbiota Transplantation)
timeFrame: Baseline, Week 1, Week 4 and Week 12
measure: Anxiety as Measured by the Hospital Anxiety and Depression Scale (HADS). HADS-A (Anxiety)
timeFrame: Baseline, Week 12 (before cross-over), Week 24
measure: Depression as Measured by the Hospital Anxiety and Depression Scale (HADS). HADS-D (Depression)
timeFrame: Baseline, Week 12 (before cross-over), Week 24
measure: Bowel Consistency as Measured by the Bristol Stool Form Scale (BSFS)
timeFrame: Baseline, Week 12 (before cross-over), Week 24
measure: Number of Participants With Adverse Events as a Measure of Safety and Tolerability
timeFrame: All AEs over 24 weeks
measure: Satisfaction With Fecal Microbiota Transplantation (FMT)
timeFrame: Week 12 following administration of FMT
measure: Change in Bowel Habits and Abdominal Pain After Fecal Microbiota Transplantation (FMT)
timeFrame: Week 12 following administration of FMT
measure: Number of Doctor or Emergency Department (ED) Visits Post-Fecal Microbiota Transplantation (Post-FMT) for Irritable Bowel Syndrome-D (IBS-D) Related Symptoms
timeFrame: Week 12 following administration of FMT
measure: Initiation of New Medications Post-FMT for the Treatment of IBS-D Symptoms
timeFrame: Week 12 following administration of FMT
measure: Patient Attitudes Towards Fecal Microbiota Transplantation (FMT)
timeFrame: Week 12 following administration of FMT
measure: Tolerability of Fecal Microbiota Transplantation (FMT)
timeFrame: Week 12 following administration of FMT
measure: Intestinal Microbiota Composition Pre- and Post-FMT (Fecal Microbiota Transplantation)
timeFrame: Baseline, Week 1, Week 4 and Week 12
measure: Intestinal Microbiota Composition Pre- and Post-FMT (Fecal Microbiota Transplantation)
timeFrame: Baseline, Week 1, Week 4 and Week 12
measure: Intestinal Microbiota Composition Pre- and Post-FMT (Fecal Microbiota Transplantation)
timeFrame: Baseline and Week 1
Other outcomes:
Locations:
city: Hamden
country: United States
facility: Medical Research Center of Connecticut
state: Connecticut
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: New York
country: United States
facility: Concorde Medical Group
state: New York
Study officials:
affiliation: Montefiore Medical Center
name: Olga C Aroniadis, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Montefiore Medical Center
name: Lawrence J Brandt, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Aroniadis OC, Brandt LJ, Oneto C, Feuerstadt P, Sherman A, Wolkoff AW, Kassam Z, Sadovsky RG, Elliott RJ, Budree S, Kim M, Keller MJ. Faecal microbiota transplantation for diarrhoea-predominant irritable bowel syndrome: a double-blind, randomised, placebo-controlled trial. Lancet Gastroenterol Hepatol. 2019 Sep;4(9):675-685. doi: 10.1016/S2468-1253(19)30198-0. Epub 2019 Jul 17.