- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02328547
Fecal Microbiota Transplantation for the Treatment of Diarrhea-Predominant Irritable Bowel Syndrome
Randomized, Double-blinded, Placebo-controlled Trial of Fecal Microbiota Transplantation (FMT) for Diarrhea-Predominant Irritable Bowel Syndrome (IBS-D)
Study Overview
Status
Conditions
Intervention / Treatment
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.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
Connecticut
-
Hamden, Connecticut, United States, 06518
- Medical Research Center of Connecticut
-
-
New York
-
Bronx, New York, United States, 10467
- Montefiore Medical Center
-
New York, New York, United States, 10016
- Concorde Medical Group
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: FMT capsules
Intervention: Fecal microbiota transplantation capsules containing extensively screened donor stool, prepared by OpenBiome, Medford, MA. 25 FMT capsules will be take on three consecutive days.
|
Fecal microbiota transplantation capsules contain extensively screened donor stool and are prepared by OpenBiome, Medford, MA.
Other Names:
|
Placebo Comparator: Placebo capsules
Intervention: Placebo capsules that do not contain donor stool or any active drug, prepared by OpenBiome, Medford, MA. 25 placebo capsules will be taken on three consecutive days.
|
Placebo capsules prepared by OpenBiome, Medford, MA
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Within and Between Group Comparisons of Disease Severity as Determined by Irritable Bowel Syndrome-Symptom Severity Score (IBS-SSS)
Time Frame: Baseline, Week 12 (before cross-over), Week 24
|
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. |
Baseline, Week 12 (before cross-over), Week 24
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Within and Between Group Comparisons of Quality of Life as Determined by the Irritable Bowel Syndrome-Quality of Life (IBS-QOL) Score
Time Frame: Baseline, Week 12 (before cross-over), Week 24
|
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 |
Baseline, Week 12 (before cross-over), Week 24
|
Intestinal Microbiota Composition Pre- and Post-FMT (Fecal Microbiota Transplantation)
Time Frame: Baseline, Week 1, Week 4 and Week 12
|
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. |
Baseline, Week 1, Week 4 and Week 12
|
Anxiety as Measured by the Hospital Anxiety and Depression Scale (HADS). HADS-A (Anxiety)
Time Frame: Baseline, Week 12 (before cross-over), Week 24
|
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 |
Baseline, Week 12 (before cross-over), Week 24
|
Depression as Measured by the Hospital Anxiety and Depression Scale (HADS). HADS-D (Depression)
Time Frame: Baseline, Week 12 (before cross-over), Week 24
|
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 |
Baseline, Week 12 (before cross-over), Week 24
|
Bowel Consistency as Measured by the Bristol Stool Form Scale (BSFS)
Time Frame: Baseline, Week 12 (before cross-over), Week 24
|
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 |
Baseline, Week 12 (before cross-over), Week 24
|
Number of Participants With Adverse Events as a Measure of Safety and Tolerability
Time Frame: All AEs over 24 weeks
|
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.
|
All AEs over 24 weeks
|
Satisfaction With Fecal Microbiota Transplantation (FMT)
Time Frame: Week 12 following administration of FMT
|
Weekly assessments of satisfaction with the Fecal Microbiota Transplantation (FMT) will be recorded in patient diaries.
|
Week 12 following administration of FMT
|
Change in Bowel Habits and Abdominal Pain After Fecal Microbiota Transplantation (FMT)
Time Frame: Week 12 following administration of FMT
|
Degree of improvement in bowel habits and abdominal pain will be recorded in patient diaries.
|
Week 12 following administration of FMT
|
Number of Doctor or Emergency Department (ED) Visits Post-Fecal Microbiota Transplantation (Post-FMT) for Irritable Bowel Syndrome-D (IBS-D) Related Symptoms
Time Frame: Week 12 following administration of FMT
|
The number of doctor or ED visits post-Fecal Microbiota Transplantation for Irritable Bowel Syndrome-D (IBS-D) related symptoms will be recorded in patient diaries.
|
Week 12 following administration of FMT
|
Initiation of New Medications Post-FMT for the Treatment of IBS-D Symptoms
Time Frame: Week 12 following administration of FMT
|
Initiation of new medications post-FMT for the treatment of IBS-D symptoms will be recorded in patient diaries.
|
Week 12 following administration of FMT
|
Patient Attitudes Towards Fecal Microbiota Transplantation (FMT)
Time Frame: Week 12 following administration of FMT
|
Patient attitudes towards Fecal Microbiota Transplantation (FMT) will be recorded in patient diaries.
|
Week 12 following administration of FMT
|
Tolerability of Fecal Microbiota Transplantation (FMT)
Time Frame: Week 12 following administration of FMT
|
Tolerability of Fecal Microbiota Transplantation (FMT) will be maintained in patient diaries.
|
Week 12 following administration of FMT
|
Intestinal Microbiota Composition Pre- and Post-FMT (Fecal Microbiota Transplantation)
Time Frame: Baseline, Week 1, Week 4 and Week 12
|
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. The Alpha Diversity Index is a quantitative measure that reflects the diversity of bacterial species in a sample. The greater the index, the more diverse the intestinal microbiota. |
Baseline, Week 1, Week 4 and Week 12
|
Intestinal Microbiota Composition Pre- and Post-FMT (Fecal Microbiota Transplantation)
Time Frame: Baseline, Week 1, Week 4 and Week 12
|
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. The Beta Diversity Index or Jensen-Shannon divergence is a quantitative measure that reflects the diversity of bacterial species between two different regions. The greater the index, the more diverse the intestinal microbiota between the two regions. |
Baseline, Week 1, Week 4 and Week 12
|
Intestinal Microbiota Composition Pre- and Post-FMT (Fecal Microbiota Transplantation)
Time Frame: Baseline and Week 1
|
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. Information on abundance of Prevotella was only available at baseline and week 1. |
Baseline and Week 1
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Olga C Aroniadis, MD, Montefiore Medical Center
- Principal Investigator: Lawrence J Brandt, MD, Montefiore Medical Center
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 2014-3941
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Irritable Bowel Syndrome
-
ProgenaBiomeRecruitingIrritable Bowel Syndrome | Irritable Bowel Syndrome With Diarrhea | Irritable Bowel Syndrome With Constipation | Irritable Bowel Syndrome Characterized by Constipation | Irritable Bowel Syndrome Mixed | Irritable Bowel Syndrome Without Diarrhea | Irritable Bowel | Irritable Bowel Syndrome Aggravated and other conditionsUnited States
-
ClasadoCR2O B.V.RecruitingIrritable Bowel Syndrome | Irritable Bowel Syndrome - Constipation | Irritable Bowel Syndrome - Diarrhoea | Irritable Bowel Syndrome - MixedBelgium, Netherlands, United Kingdom
-
Istanbul Medipol University HospitalTepecik Training and Research Hospital; Bozyaka Training and Research Hospital and other collaboratorsRecruitingIrritable Bowel Syndrome | Irritable Bowel Syndrome With Diarrhea | Irritable Bowel Syndrome With Constipation | Irritable Bowel Syndrome MixedTurkey
-
Federal Stare Budgetary Scientific Institution,...I.M. Sechenov First Moscow State Medical University; RML INVEST, Torkhovsky...CompletedIrritable Bowel Syndrome | Irritable Bowel Syndrome With Diarrhea | Irritable Bowel Syndrome With Constipation | Irritable Bowel Syndrome MixedRussian Federation
-
University of California, Los AngelesCompletedIrritable Bowel Syndrome With Diarrhea | Irritable Bowel Syndrome With Mixed Bowel HabitsUnited States
-
University of ViennaCompleted
-
Thomayer University HospitalCharles University, Czech RepublicActive, not recruitingIrritable Bowel Syndrome With Diarrhea | Irritable Bowel Syndrome MixedCzechia
-
Shahid Beheshti University of Medical SciencesCompletedIrritable Bowel DiseaseIran, Islamic Republic of
-
Universidad Autonoma de ChihuahuaNot yet recruitingIrritable Bowel Syndrome | Constipation-predominant Irritable Bowel Syndrome | Diarrhea- Irritable Bowel Syndrome
-
Vasily IsakovRussian Science Foundation; Azbuka vkusa; Federal Research Centre of Nutrition...CompletedIrritable Bowel Syndrome With Constipation | Constipation-predominant Irritable Bowel SyndromeRussian Federation
Clinical Trials on Fecal microbiota transplantation capsules
-
Massachusetts General HospitalUniversity of California, San DiegoNot yet recruitingAuto-Brewery Syndrome | Gut Fermentation SyndromeUnited States
-
Alice Højer ChristensenCompleted
-
Xiangyu KongNot yet recruitingAdvanced Gastric CancerChina
-
Madhusudan (Madhu) Grover, MBBSRecruiting
-
Medical University of GrazBristol-Myers SquibbTerminatedMalignant Melanoma Stage III | Malignant Melanoma Stage IV | Fecal Microbiota TransplantationAustria
-
Assistance Publique - Hôpitaux de ParisRecruitingEnterobacteriaceae Infections | Fecal Microbiota TransplantationFrance
-
Children's Mercy Hospital Kansas CityUniversity of Pittsburgh; Stanford UniversityCompletedUlcerative Colitis (UC) | Inflammatory Bowel Diseases (IBD) | Crohn's Disease (CD)United States
-
The Second Hospital of Nanjing Medical UniversitySIR RUN RUN hospital of Nanjing Medical UniversityNot yet recruitingAttention-deficit/Hyperactivity DisorderChina
-
The Second Hospital of Nanjing Medical UniversityNot yet recruiting
-
The Second Hospital of Nanjing Medical UniversitySIR RUN RUN hospital of Nanjing Medical UniversityNot yet recruitingAutism Spectrum Disorder