Irritable Bowel Syndrome
Conditions
Keywords
fecal microbiota transplantation, diarrhea-predominant
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.
Interventions
Fecal microbiota transplantation capsules contain extensively screened donor stool and are prepared by OpenBiome, Medford, MA.
DRUGPlacebo capsules
Placebo capsules prepared by OpenBiome, Medford, MA
Sponsors
Montefiore Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
19 Years to 65 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Within and Between Group Comparisons of Disease Severity as Determined by Irritable Bowel Syndrome-Symptom Severity Score (IBS-SSS) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Intestinal Microbiota Composition Pre- and Post-FMT (Fecal Microbiota Transplantation) | 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. |
| Anxiety as Measured by the Hospital Anxiety and Depression Scale (HADS). HADS-A (Anxiety) | 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 |
| Depression as Measured by the Hospital Anxiety and Depression Scale (HADS). HADS-D (Depression) | 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 |
| Bowel Consistency as Measured by the Bristol Stool Form Scale (BSFS) | 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 |
| Number of Participants With Adverse Events as a Measure of Safety and Tolerability | 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. |
| Within and Between Group Comparisons of Quality of Life as Determined by the Irritable Bowel Syndrome-Quality of Life (IBS-QOL) Score | 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 |
| Change in Bowel Habits and Abdominal Pain After Fecal Microbiota Transplantation (FMT) | Week 12 following administration of FMT | Degree of improvement in bowel habits and abdominal pain will be recorded in patient diaries. |
| Number of Doctor or Emergency Department (ED) Visits Post-Fecal Microbiota Transplantation (Post-FMT) for Irritable Bowel Syndrome-D (IBS-D) Related Symptoms | 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. |
| Initiation of New Medications Post-FMT for the Treatment of IBS-D Symptoms | 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. |
| Patient Attitudes Towards Fecal Microbiota Transplantation (FMT) | Week 12 following administration of FMT | Patient attitudes towards Fecal Microbiota Transplantation (FMT) will be recorded in patient diaries. |
| Tolerability of Fecal Microbiota Transplantation (FMT) | Week 12 following administration of FMT | Tolerability of Fecal Microbiota Transplantation (FMT) will be maintained in patient diaries. |
| Satisfaction With Fecal Microbiota Transplantation (FMT) | Week 12 following administration of FMT | Weekly assessments of satisfaction with the Fecal Microbiota Transplantation (FMT) will be recorded in patient diaries. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Fecal Microbiota Transplantation Capsules First, Then Placebo Intervention: 25 Fecal Microbiota Transplantation (FMT) capsules were administered on each of three consecutive days (Day 1, Day 2, Day 3), then patients were followed for 12 weeks. At 12 weeks, patients crossed over into the alternate arm and received placebo capsules on each of three consecutive days (Day 1, Day 2, Day 3). At 12 weeks, patients crossed over into the alternate arm and received placebo capsules on each of three consecutive days (Day 1, Day 2, Day 3).
FMT capsules contained extensively screened donor stool and are prepared by OpenBiome. Placebo capsules contained saline and glycerol. Both FMT and Placebo capsules were prepared by OpenBiome, Medford, MA. | 25 |
| Placebo Capsules First, Then Fecal Microbiota Transplantation Intervention: 25 Placebo capsules, that did not contain donor stool or active drug, were administered on each of three consecutive days (Day 1, Day 2, Day 3), then patients were followed for 12 weeks. At 12 weeks, patients crossed over into the alternate arm and received fecal microbiota transplantation capsules on each of three consecutive days (Day 1, Day 2, Day 3).
FMT capsules contained extensively screened donor stool and are prepared by OpenBiome. Placebo capsules contained saline and glycerol. Both FMT and Placebo capsules were prepared by OpenBiome, Medford, MA. | 23 |
| Total | 48 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| First Intervention (12 Weeks) | Lost to Follow-up | 1 | 0 |
| First Intervention (12 Weeks) | Withdrawal by Subject | 2 | 0 |
Baseline characteristics
| Characteristic | Total | Placebo Capsules First, Then Fecal Microbiota Transplantation | Fecal Microbiota Transplantation Capsules First, Then Placebo |
|---|---|---|---|
| Age, Continuous | 38.4 years STANDARD_DEVIATION 12 | 39.0 years STANDARD_DEVIATION 11.7 | 37.8 years STANDARD_DEVIATION 12.3 |
| Bristol Stool Form Scale (BSFS) | 6.0 units on a scale STANDARD_DEVIATION 0.9 | 6.0 units on a scale STANDARD_DEVIATION 0.9 | 5.0 units on a scale STANDARD_DEVIATION 0.8 |
| Hospital Anxiety and Depression Scale (HADS). HADS-A (Anxiety) | 7.8 units on a scale STANDARD_DEVIATION 4.2 | 7.2 units on a scale STANDARD_DEVIATION 3.6 | 8.3 units on a scale STANDARD_DEVIATION 4.7 |
| Hospital Anxiety and Depression Scale (HADS) HADS-D (Depression) | 4.8 units on a scale STANDARD_DEVIATION 3.7 | 5.1 units on a scale STANDARD_DEVIATION 3 | 4.6 units on a scale STANDARD_DEVIATION 4.3 |
| IBS-QOL | 52 units on a scale STANDARD_DEVIATION 18 | 52 units on a scale STANDARD_DEVIATION 18 | 53 units on a scale STANDARD_DEVIATION 18 |
| IBS-SSS | 294 units on a scale STANDARD_DEVIATION 65 | 309 units on a scale STANDARD_DEVIATION 64 | 282 units on a scale STANDARD_DEVIATION 65 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 4 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 4 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 40 Participants | 19 Participants | 21 Participants |
| Region of Enrollment United States | 48 participants | 23 participants | 25 participants |
| Sex: Female, Male Female | 18 Participants | 9 Participants | 9 Participants |
| Sex: Female, Male Male | 30 Participants | 14 Participants | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 48 | 0 / 48 |
| other Total, other adverse events | 23 / 48 | 24 / 48 |
| serious Total, serious adverse events | 0 / 48 | 1 / 48 |
Outcome results
Primary
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
Population: Participants were randomized to FMT first followed by placebo (n=25) OR to placebo first followed by FMT (n=23) and analyzed in these groups. Participants who received FMT 1st and those who received FMT 2nd were not pooled together into one group because of potential carry-over effects.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| FMT Capsules, Followed by Placebo Capsules | Within and Between Group Comparisons of Disease Severity as Determined by Irritable Bowel Syndrome-Symptom Severity Score (IBS-SSS) | Baseline | 282 units on a scale | Standard Deviation 65 |
| FMT Capsules, Followed by Placebo Capsules | Within and Between Group Comparisons of Disease Severity as Determined by Irritable Bowel Syndrome-Symptom Severity Score (IBS-SSS) | Week 12 | 221 units on a scale | Standard Deviation 105 |
| FMT Capsules, Followed by Placebo Capsules | Within and Between Group Comparisons of Disease Severity as Determined by Irritable Bowel Syndrome-Symptom Severity Score (IBS-SSS) | Week 24 | 208 units on a scale | Standard Deviation 111 |
| Placebo Capsules, Followed by FMT Capsules | Within and Between Group Comparisons of Disease Severity as Determined by Irritable Bowel Syndrome-Symptom Severity Score (IBS-SSS) | Baseline | 309 units on a scale | Standard Deviation 64 |
| Placebo Capsules, Followed by FMT Capsules | Within and Between Group Comparisons of Disease Severity as Determined by Irritable Bowel Syndrome-Symptom Severity Score (IBS-SSS) | Week 12 | 236 units on a scale | Standard Deviation 95 |
| Placebo Capsules, Followed by FMT Capsules | Within and Between Group Comparisons of Disease Severity as Determined by Irritable Bowel Syndrome-Symptom Severity Score (IBS-SSS) | Week 24 | 157 units on a scale | Standard Deviation 101 |
Secondary
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
Population: Participants were randomized to FMT first followed by placebo (n=25) OR to placebo first followed by FMT (n=23) and analyzed in these groups. Participants who received FMT 1st and those who received FMT 2nd were not pooled together into one group because of potential carry-over effects. As such, data for crossover intervention couldn't be reported.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| FMT Capsules, Followed by Placebo Capsules | Anxiety as Measured by the Hospital Anxiety and Depression Scale (HADS). HADS-A (Anxiety) | Baseline | 8.3 score on a scale | Standard Deviation 4.7 |
| FMT Capsules, Followed by Placebo Capsules | Anxiety as Measured by the Hospital Anxiety and Depression Scale (HADS). HADS-A (Anxiety) | Week 12 | 8.6 score on a scale | Standard Deviation 5 |
| FMT Capsules, Followed by Placebo Capsules | Anxiety as Measured by the Hospital Anxiety and Depression Scale (HADS). HADS-A (Anxiety) | Week 24 | 7.9 score on a scale | Standard Deviation 4.8 |
| Placebo Capsules, Followed by FMT Capsules | Anxiety as Measured by the Hospital Anxiety and Depression Scale (HADS). HADS-A (Anxiety) | Baseline | 7.2 score on a scale | Standard Deviation 3.6 |
| Placebo Capsules, Followed by FMT Capsules | Anxiety as Measured by the Hospital Anxiety and Depression Scale (HADS). HADS-A (Anxiety) | Week 12 | 7.4 score on a scale | Standard Deviation 4.6 |
| Placebo Capsules, Followed by FMT Capsules | Anxiety as Measured by the Hospital Anxiety and Depression Scale (HADS). HADS-A (Anxiety) | Week 24 | 5.6 score on a scale | Standard Deviation 3.6 |
Secondary
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
Population: Participants were randomized to FMT first followed by placebo (n=25) OR to placebo first followed by FMT (n=23) and analyzed in these groups. Participants who received FMT 1st and those who received FMT 2nd were not pooled together into one group because of potential carry-over effects. As such, data for crossover intervention couldn't be reported.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| FMT Capsules, Followed by Placebo Capsules | Bowel Consistency as Measured by the Bristol Stool Form Scale (BSFS) | Baseline | 5 score on a scale | Standard Deviation 0.8 |
| FMT Capsules, Followed by Placebo Capsules | Bowel Consistency as Measured by the Bristol Stool Form Scale (BSFS) | Week 12 | 4 score on a scale | Standard Deviation 1 |
| FMT Capsules, Followed by Placebo Capsules | Bowel Consistency as Measured by the Bristol Stool Form Scale (BSFS) | Week 24 | 4 score on a scale | Standard Deviation 1 |
| Placebo Capsules, Followed by FMT Capsules | Bowel Consistency as Measured by the Bristol Stool Form Scale (BSFS) | Baseline | 6 score on a scale | Standard Deviation 0.9 |
| Placebo Capsules, Followed by FMT Capsules | Bowel Consistency as Measured by the Bristol Stool Form Scale (BSFS) | Week 12 | 5 score on a scale | Standard Deviation 1.1 |
| Placebo Capsules, Followed by FMT Capsules | Bowel Consistency as Measured by the Bristol Stool Form Scale (BSFS) | Week 24 | 4 score on a scale | Standard Deviation 1.3 |
Secondary
Change in Bowel Habits and Abdominal Pain After Fecal Microbiota Transplantation (FMT)
Degree of improvement in bowel habits and abdominal pain will be recorded in patient diaries.
Time frame: Week 12 following administration of FMT
Population: Data was not collected and, therefore, the outcome cannot be reported.
Secondary
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
Population: Participants were randomized to FMT first followed by placebo (n=25) OR to placebo first followed by FMT (n=23) and analyzed in these groups. Participants who received FMT 1st and those who received FMT 2nd were not pooled together into one group because of potential carry-over effects. As such, data for crossover intervention couldn't be reported.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| FMT Capsules, Followed by Placebo Capsules | Depression as Measured by the Hospital Anxiety and Depression Scale (HADS). HADS-D (Depression) | Baseline | 4.6 score on a scale | Standard Deviation 4.3 |
| FMT Capsules, Followed by Placebo Capsules | Depression as Measured by the Hospital Anxiety and Depression Scale (HADS). HADS-D (Depression) | Week 12 | 4.0 score on a scale | Standard Deviation 4.1 |
| FMT Capsules, Followed by Placebo Capsules | Depression as Measured by the Hospital Anxiety and Depression Scale (HADS). HADS-D (Depression) | Week 24 | 3.8 score on a scale | Standard Deviation 3.5 |
| Placebo Capsules, Followed by FMT Capsules | Depression as Measured by the Hospital Anxiety and Depression Scale (HADS). HADS-D (Depression) | Baseline | 5.1 score on a scale | Standard Deviation 3 |
| Placebo Capsules, Followed by FMT Capsules | Depression as Measured by the Hospital Anxiety and Depression Scale (HADS). HADS-D (Depression) | Week 12 | 4.0 score on a scale | Standard Deviation 2.6 |
| Placebo Capsules, Followed by FMT Capsules | Depression as Measured by the Hospital Anxiety and Depression Scale (HADS). HADS-D (Depression) | Week 24 | 3.4 score on a scale | Standard Deviation 2.8 |
Secondary
Initiation of New Medications Post-FMT for the Treatment of IBS-D Symptoms
Initiation of new medications post-FMT for the treatment of IBS-D symptoms will be recorded in patient diaries.
Time frame: Week 12 following administration of FMT
Population: Data was not collected and, therefore, the outcome cannot be reported.
Secondary
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. 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.
Time frame: Baseline, Week 1, Week 4 and Week 12
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| FMT Capsules, Followed by Placebo Capsules | Intestinal Microbiota Composition Pre- and Post-FMT (Fecal Microbiota Transplantation) | Alpha Diversity - Baseline | 3.96 index | Standard Deviation 0.43 |
| FMT Capsules, Followed by Placebo Capsules | Intestinal Microbiota Composition Pre- and Post-FMT (Fecal Microbiota Transplantation) | Alpha-Diversity - Week 1 | 4.00 index | Standard Deviation 0.41 |
| FMT Capsules, Followed by Placebo Capsules | Intestinal Microbiota Composition Pre- and Post-FMT (Fecal Microbiota Transplantation) | Alpha Diversity - Week 4 | 4.05 index | Standard Deviation 0.59 |
| FMT Capsules, Followed by Placebo Capsules | Intestinal Microbiota Composition Pre- and Post-FMT (Fecal Microbiota Transplantation) | Alpha Diversity - Week 12 | 4.02 index | Standard Deviation 0.62 |
| Placebo Capsules, Followed by FMT Capsules | Intestinal Microbiota Composition Pre- and Post-FMT (Fecal Microbiota Transplantation) | Alpha Diversity - Week 12 | 4.29 index | Standard Deviation 0.29 |
| Placebo Capsules, Followed by FMT Capsules | Intestinal Microbiota Composition Pre- and Post-FMT (Fecal Microbiota Transplantation) | Alpha Diversity - Baseline | 4.16 index | Standard Deviation 0.41 |
| Placebo Capsules, Followed by FMT Capsules | Intestinal Microbiota Composition Pre- and Post-FMT (Fecal Microbiota Transplantation) | Alpha Diversity - Week 4 | 4.29 index | Standard Deviation 0.29 |
| Placebo Capsules, Followed by FMT Capsules | Intestinal Microbiota Composition Pre- and Post-FMT (Fecal Microbiota Transplantation) | Alpha-Diversity - Week 1 | 4.13 index | Standard Deviation 0.28 |
Secondary
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. Information on abundance of Prevotella was only available at baseline and week 1.
Time frame: Baseline and Week 1
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| FMT Capsules, Followed by Placebo Capsules | Intestinal Microbiota Composition Pre- and Post-FMT (Fecal Microbiota Transplantation) | Prevotella - Baseline | 0.12 percentage of bacteria | Standard Deviation 0.18 |
| FMT Capsules, Followed by Placebo Capsules | Intestinal Microbiota Composition Pre- and Post-FMT (Fecal Microbiota Transplantation) | Prevotella - Week 1 | 0.14 percentage of bacteria | Standard Deviation 0.19 |
| Placebo Capsules, Followed by FMT Capsules | Intestinal Microbiota Composition Pre- and Post-FMT (Fecal Microbiota Transplantation) | Prevotella - Baseline | 0.04 percentage of bacteria | Standard Deviation 0.12 |
| Placebo Capsules, Followed by FMT Capsules | Intestinal Microbiota Composition Pre- and Post-FMT (Fecal Microbiota Transplantation) | Prevotella - Week 1 | 0.03 percentage of bacteria | Standard Deviation 0.09 |
Secondary
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.
Time frame: Baseline, Week 1, Week 4 and Week 12
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| FMT Capsules, Followed by Placebo Capsules | Intestinal Microbiota Composition Pre- and Post-FMT (Fecal Microbiota Transplantation) | Firmicutes - Baseline | 0.51 percentage of bacteria | Standard Deviation 0.19 |
| FMT Capsules, Followed by Placebo Capsules | Intestinal Microbiota Composition Pre- and Post-FMT (Fecal Microbiota Transplantation) | Firmicutes - Week 1 | 0.50 percentage of bacteria | Standard Deviation 0.15 |
| FMT Capsules, Followed by Placebo Capsules | Intestinal Microbiota Composition Pre- and Post-FMT (Fecal Microbiota Transplantation) | Firmicutes - Week 4 | 0.50 percentage of bacteria | Standard Deviation 0.13 |
| FMT Capsules, Followed by Placebo Capsules | Intestinal Microbiota Composition Pre- and Post-FMT (Fecal Microbiota Transplantation) | Firmicutes - Week 12 | 0.46 percentage of bacteria | Standard Deviation 0.12 |
| Placebo Capsules, Followed by FMT Capsules | Intestinal Microbiota Composition Pre- and Post-FMT (Fecal Microbiota Transplantation) | Firmicutes - Week 12 | 0.56 percentage of bacteria | Standard Deviation 0.09 |
| Placebo Capsules, Followed by FMT Capsules | Intestinal Microbiota Composition Pre- and Post-FMT (Fecal Microbiota Transplantation) | Firmicutes - Baseline | 0.55 percentage of bacteria | Standard Deviation 0.12 |
| Placebo Capsules, Followed by FMT Capsules | Intestinal Microbiota Composition Pre- and Post-FMT (Fecal Microbiota Transplantation) | Firmicutes - Week 4 | 0.57 percentage of bacteria | Standard Deviation 0.12 |
| Placebo Capsules, Followed by FMT Capsules | Intestinal Microbiota Composition Pre- and Post-FMT (Fecal Microbiota Transplantation) | Firmicutes - Week 1 | 0.54 percentage of bacteria | Standard Deviation 0.11 |
Secondary
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.
Time frame: Baseline, Week 1, Week 4 and Week 12
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| FMT Capsules, Followed by Placebo Capsules | Intestinal Microbiota Composition Pre- and Post-FMT (Fecal Microbiota Transplantation) | Bacteroidetes - Baseline | 0.41 percentage of bacteria | Standard Deviation 0.19 |
| FMT Capsules, Followed by Placebo Capsules | Intestinal Microbiota Composition Pre- and Post-FMT (Fecal Microbiota Transplantation) | Bacteroidetes - Week 1 | 0.43 percentage of bacteria | Standard Deviation 0.15 |
| FMT Capsules, Followed by Placebo Capsules | Intestinal Microbiota Composition Pre- and Post-FMT (Fecal Microbiota Transplantation) | Bacteroidetes - Week 4 | 0.38 percentage of bacteria | Standard Deviation 0.14 |
| FMT Capsules, Followed by Placebo Capsules | Intestinal Microbiota Composition Pre- and Post-FMT (Fecal Microbiota Transplantation) | Bacteroidetes - Week 12 | 0.47 percentage of bacteria | Standard Deviation 0.14 |
| Placebo Capsules, Followed by FMT Capsules | Intestinal Microbiota Composition Pre- and Post-FMT (Fecal Microbiota Transplantation) | Bacteroidetes - Week 12 | 0.34 percentage of bacteria | Standard Deviation 0.1 |
| Placebo Capsules, Followed by FMT Capsules | Intestinal Microbiota Composition Pre- and Post-FMT (Fecal Microbiota Transplantation) | Bacteroidetes - Baseline | 0.35 percentage of bacteria | Standard Deviation 0.1 |
| Placebo Capsules, Followed by FMT Capsules | Intestinal Microbiota Composition Pre- and Post-FMT (Fecal Microbiota Transplantation) | Bacteroidetes - Week 4 | 0.34 percentage of bacteria | Standard Deviation 0.09 |
| Placebo Capsules, Followed by FMT Capsules | Intestinal Microbiota Composition Pre- and Post-FMT (Fecal Microbiota Transplantation) | Bacteroidetes - Week 1 | 0.34 percentage of bacteria | Standard Deviation 0.1 |
Secondary
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. 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.
Time frame: Baseline, Week 1, Week 4 and Week 12
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| FMT Capsules, Followed by Placebo Capsules | Intestinal Microbiota Composition Pre- and Post-FMT (Fecal Microbiota Transplantation) | Jensen-Shannon Diversity - Baseline | 0.52 index | Standard Deviation 0.12 |
| FMT Capsules, Followed by Placebo Capsules | Intestinal Microbiota Composition Pre- and Post-FMT (Fecal Microbiota Transplantation) | Jensen-Shannon Diversity - Week 1 | 0.44 index | Standard Deviation 0.16 |
| FMT Capsules, Followed by Placebo Capsules | Intestinal Microbiota Composition Pre- and Post-FMT (Fecal Microbiota Transplantation) | Jensen Shannon Diversity - Week 4 | 0.43 index | Standard Deviation 0.14 |
| FMT Capsules, Followed by Placebo Capsules | Intestinal Microbiota Composition Pre- and Post-FMT (Fecal Microbiota Transplantation) | Jensen Shannon Diversity - Week 12 | 0.41 index | Standard Deviation 0.16 |
| Placebo Capsules, Followed by FMT Capsules | Intestinal Microbiota Composition Pre- and Post-FMT (Fecal Microbiota Transplantation) | Jensen Shannon Diversity - Week 12 | 0.40 index | Standard Deviation 0.15 |
| Placebo Capsules, Followed by FMT Capsules | Intestinal Microbiota Composition Pre- and Post-FMT (Fecal Microbiota Transplantation) | Jensen-Shannon Diversity - Baseline | 0.48 index | Standard Deviation 0.22 |
| Placebo Capsules, Followed by FMT Capsules | Intestinal Microbiota Composition Pre- and Post-FMT (Fecal Microbiota Transplantation) | Jensen Shannon Diversity - Week 4 | 0.38 index | Standard Deviation 0.16 |
| Placebo Capsules, Followed by FMT Capsules | Intestinal Microbiota Composition Pre- and Post-FMT (Fecal Microbiota Transplantation) | Jensen-Shannon Diversity - Week 1 | 0.40 index | Standard Deviation 0.16 |
Secondary
Number of Doctor or Emergency Department (ED) Visits Post-Fecal Microbiota Transplantation (Post-FMT) for Irritable Bowel Syndrome-D (IBS-D) Related Symptoms
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.
Time frame: Week 12 following administration of FMT
Population: Data was not collected and, therefore, the outcome cannot be reported.
Secondary
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
Population: Participants were randomized to FMT first followed by placebo (n=25) OR to placebo first followed by FMT (n=23) and analyzed in these groups. Participants who received FMT 1st and those who received FMT 2nd were pooled together into one group.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| FMT Capsules, Followed by Placebo Capsules | Number of Participants With Adverse Events as a Measure of Safety and Tolerability | Any Adverse Event | 23 Participants |
| FMT Capsules, Followed by Placebo Capsules | Number of Participants With Adverse Events as a Measure of Safety and Tolerability | No Adverse Events | 25 Participants |
| Placebo Capsules, Followed by FMT Capsules | Number of Participants With Adverse Events as a Measure of Safety and Tolerability | Any Adverse Event | 24 Participants |
| Placebo Capsules, Followed by FMT Capsules | Number of Participants With Adverse Events as a Measure of Safety and Tolerability | No Adverse Events | 24 Participants |
Secondary
Patient Attitudes Towards Fecal Microbiota Transplantation (FMT)
Patient attitudes towards Fecal Microbiota Transplantation (FMT) will be recorded in patient diaries.
Time frame: Week 12 following administration of FMT
Population: Data was not collected and, therefore, the outcome cannot be reported.
Secondary
Satisfaction With Fecal Microbiota Transplantation (FMT)
Weekly assessments of satisfaction with the Fecal Microbiota Transplantation (FMT) will be recorded in patient diaries.
Time frame: Week 12 following administration of FMT
Population: Data was not collected and, therefore, the outcome cannot be reported.
Secondary
Tolerability of Fecal Microbiota Transplantation (FMT)
Tolerability of Fecal Microbiota Transplantation (FMT) will be maintained in patient diaries.
Time frame: Week 12 following administration of FMT
Population: Data was not collected and, therefore, the outcome cannot be reported.
Secondary
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
Population: Participants were randomized to FMT first followed by placebo (n=25) OR to placebo first followed by FMT (n=23) and analyzed in these groups. Participants who received FMT 1st and those who received FMT 2nd were not pooled together into one group because of potential carry-over effects. As such, data for crossover intervention couldn't be reported.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| FMT Capsules, Followed by Placebo Capsules | Within and Between Group Comparisons of Quality of Life as Determined by the Irritable Bowel Syndrome-Quality of Life (IBS-QOL) Score | Baseline | 53 units on a scale | Standard Deviation 18 |
| FMT Capsules, Followed by Placebo Capsules | Within and Between Group Comparisons of Quality of Life as Determined by the Irritable Bowel Syndrome-Quality of Life (IBS-QOL) Score | Week 12 | 65 units on a scale | Standard Deviation 18 |
| FMT Capsules, Followed by Placebo Capsules | Within and Between Group Comparisons of Quality of Life as Determined by the Irritable Bowel Syndrome-Quality of Life (IBS-QOL) Score | Week 24 | 70 units on a scale | Standard Deviation 18 |
| Placebo Capsules, Followed by FMT Capsules | Within and Between Group Comparisons of Quality of Life as Determined by the Irritable Bowel Syndrome-Quality of Life (IBS-QOL) Score | Baseline | 52 units on a scale | Standard Deviation 18 |
| Placebo Capsules, Followed by FMT Capsules | Within and Between Group Comparisons of Quality of Life as Determined by the Irritable Bowel Syndrome-Quality of Life (IBS-QOL) Score | Week 12 | 66 units on a scale | Standard Deviation 17 |
| Placebo Capsules, Followed by FMT Capsules | Within and Between Group Comparisons of Quality of Life as Determined by the Irritable Bowel Syndrome-Quality of Life (IBS-QOL) Score | Week 24 | 76 units on a scale | Standard Deviation 17 |