Trial Outcomes & Findings for Fecal Microbiota Transplantation for the Treatment of Diarrhea-Predominant Irritable Bowel Syndrome (NCT NCT02328547)

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

48 participants

Primary outcome timeframe

Baseline, Week 12 (before cross-over), Week 24

Results posted on

2019-07-02

Participant Flow

Participant milestones

Participant milestones
Measure	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). Patients were seen on Day 10, Week 4, Week 8, and Week 12 after FMT administration. Patients were crossed-over into the Placebo arm at 12 weeks. After cross-over, patients were administered 25 Placebo capsules, that did not contain donor stool or active drug, on each of three consecutive days (Day 1, Day 2, Day 3). Patients were seen on Day 10, Week 4, Week 8, and Week 12 after Placebo dosing. The overall duration of the study was 6 months. 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.	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). Patients were seen on Day 10, Week 4, Week 8, and Week 12 after Placebo administration. Patients were then crossed-over into the FMT arm at 12 weeks. After cross-over, patients were administered 25 Fecal Microbiota Transplantation (FMT) capsules on each of three consecutive days (Day 1, Day 2, Day 3). Patients were seen on Day 10, Week 4, Week 8, and Week 12 after FMT administration. The overall duration of the study was 6 months. 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.
First Intervention (12 Weeks) STARTED	25	23
First Intervention (12 Weeks) COMPLETED	22	23
First Intervention (12 Weeks) NOT COMPLETED	3	0
Second Intervention (12 Weeks) STARTED	22	23
Second Intervention (12 Weeks) COMPLETED	22	23
Second Intervention (12 Weeks) NOT COMPLETED	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	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). Patients were seen on Day 10, Week 4, Week 8, and Week 12 after FMT administration. Patients were crossed-over into the Placebo arm at 12 weeks. After cross-over, patients were administered 25 Placebo capsules, that did not contain donor stool or active drug, on each of three consecutive days (Day 1, Day 2, Day 3). Patients were seen on Day 10, Week 4, Week 8, and Week 12 after Placebo dosing. The overall duration of the study was 6 months. 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.	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). Patients were seen on Day 10, Week 4, Week 8, and Week 12 after Placebo administration. Patients were then crossed-over into the FMT arm at 12 weeks. After cross-over, patients were administered 25 Fecal Microbiota Transplantation (FMT) capsules on each of three consecutive days (Day 1, Day 2, Day 3). Patients were seen on Day 10, Week 4, Week 8, and Week 12 after FMT administration. The overall duration of the study was 6 months. 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.
First Intervention (12 Weeks) Lost to Follow-up	1	0
First Intervention (12 Weeks) Withdrawal by Subject	2	0

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Fecal Microbiota Transplantation Capsules First, Then Placebo n=25 Participants 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.	Placebo Capsules First, Then Fecal Microbiota Transplantation n=23 Participants 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.	Total n=48 Participants Total of all reporting groups
Age, Continuous	37.8 years STANDARD_DEVIATION 12.3 • n=5 Participants	39.0 years STANDARD_DEVIATION 11.7 • n=7 Participants	38.4 years STANDARD_DEVIATION 12.0 • n=5 Participants
Sex: Female, Male Female	9 Participants n=5 Participants	9 Participants n=7 Participants	18 Participants n=5 Participants
Sex: Female, Male Male	16 Participants n=5 Participants	14 Participants n=7 Participants	30 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	21 Participants n=5 Participants	19 Participants n=7 Participants	40 Participants n=5 Participants
Race (NIH/OMB) More than one race	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	25 participants n=5 Participants	23 participants n=7 Participants	48 participants n=5 Participants
IBS-SSS	282 units on a scale STANDARD_DEVIATION 65 • n=5 Participants	309 units on a scale STANDARD_DEVIATION 64 • n=7 Participants	294 units on a scale STANDARD_DEVIATION 65 • n=5 Participants
IBS-QOL	53 units on a scale STANDARD_DEVIATION 18 • n=5 Participants	52 units on a scale STANDARD_DEVIATION 18 • n=7 Participants	52 units on a scale STANDARD_DEVIATION 18 • n=5 Participants
Hospital Anxiety and Depression Scale (HADS). HADS-A (Anxiety)	8.3 units on a scale STANDARD_DEVIATION 4.7 • n=5 Participants	7.2 units on a scale STANDARD_DEVIATION 3.6 • n=7 Participants	7.8 units on a scale STANDARD_DEVIATION 4.2 • n=5 Participants
Hospital Anxiety and Depression Scale (HADS) HADS-D (Depression)	4.6 units on a scale STANDARD_DEVIATION 4.3 • n=5 Participants	5.1 units on a scale STANDARD_DEVIATION 3.0 • n=7 Participants	4.8 units on a scale STANDARD_DEVIATION 3.7 • n=5 Participants
Bristol Stool Form Scale (BSFS)	5.0 units on a scale STANDARD_DEVIATION 0.8 • n=5 Participants	6.0 units on a scale STANDARD_DEVIATION 0.9 • n=7 Participants	6.0 units on a scale STANDARD_DEVIATION 0.9 • n=5 Participants

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	FMT Capsules, Followed by Placebo Capsules n=25 Participants 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). Analyses included change in outcome measure between baseline and 12 weeks.	Placebo Capsules, Followed by FMT Capsules n=23 Participants Intervention: 25 placebo 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 fecal microbiota transplantation capsules on each of three consecutive days (Day 1, Day 2, Day 3). Analyses included change in outcome measure between baseline and 12 weeks.
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	309 units on a scale Standard Deviation 64
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	236 units on a scale Standard Deviation 95
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	157 units on a scale Standard Deviation 101

SECONDARY outcome

Timeframe: 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.

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

Outcome measures

Outcome measures
Measure	FMT Capsules, Followed by Placebo Capsules n=25 Participants 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). Analyses included change in outcome measure between baseline and 12 weeks.	Placebo Capsules, Followed by FMT Capsules n=23 Participants Intervention: 25 placebo 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 fecal microbiota transplantation capsules on each of three consecutive days (Day 1, Day 2, Day 3). Analyses included change in outcome measure between baseline and 12 weeks.
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	52 units on a scale Standard Deviation 18
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	66 units on a scale Standard Deviation 17
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	76 units on a scale Standard Deviation 17

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	FMT Capsules, Followed by Placebo Capsules n=11 Participants 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). Analyses included change in outcome measure between baseline and 12 weeks.	Placebo Capsules, Followed by FMT Capsules n=11 Participants Intervention: 25 placebo 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 fecal microbiota transplantation capsules on each of three consecutive days (Day 1, Day 2, Day 3). Analyses included change in outcome measure between baseline and 12 weeks.
Intestinal Microbiota Composition Pre- and Post-FMT (Fecal Microbiota Transplantation) Bacteroidetes - Baseline	0.41 percentage of bacteria Standard Deviation 0.19	0.35 percentage of bacteria Standard Deviation 0.10
Intestinal Microbiota Composition Pre- and Post-FMT (Fecal Microbiota Transplantation) Bacteroidetes - Week 1	0.43 percentage of bacteria Standard Deviation 0.15	0.34 percentage of bacteria Standard Deviation 0.10
Intestinal Microbiota Composition Pre- and Post-FMT (Fecal Microbiota Transplantation) Bacteroidetes - Week 4	0.38 percentage of bacteria Standard Deviation 0.14	0.34 percentage of bacteria Standard Deviation 0.09
Intestinal Microbiota Composition Pre- and Post-FMT (Fecal Microbiota Transplantation) Bacteroidetes - Week 12	0.47 percentage of bacteria Standard Deviation 0.14	0.34 percentage of bacteria Standard Deviation 0.10

SECONDARY outcome

Timeframe: 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.

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

Outcome measures

Outcome measures
Measure	FMT Capsules, Followed by Placebo Capsules n=25 Participants 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). Analyses included change in outcome measure between baseline and 12 weeks.	Placebo Capsules, Followed by FMT Capsules n=23 Participants Intervention: 25 placebo 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 fecal microbiota transplantation capsules on each of three consecutive days (Day 1, Day 2, Day 3). Analyses included change in outcome measure between baseline and 12 weeks.
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	7.2 score on a scale Standard Deviation 3.6
Anxiety as Measured by the Hospital Anxiety and Depression Scale (HADS). HADS-A (Anxiety) Week 12	8.6 score on a scale Standard Deviation 5.0	7.4 score on a scale Standard Deviation 4.6
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	5.6 score on a scale Standard Deviation 3.6

SECONDARY outcome

Timeframe: 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.

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

Outcome measures

Outcome measures
Measure	FMT Capsules, Followed by Placebo Capsules n=25 Participants 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). Analyses included change in outcome measure between baseline and 12 weeks.	Placebo Capsules, Followed by FMT Capsules n=23 Participants Intervention: 25 placebo 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 fecal microbiota transplantation capsules on each of three consecutive days (Day 1, Day 2, Day 3). Analyses included change in outcome measure between baseline and 12 weeks.
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	5.1 score on a scale Standard Deviation 3.0
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	4.0 score on a scale Standard Deviation 2.6
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	3.4 score on a scale Standard Deviation 2.8

SECONDARY outcome

Timeframe: 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.

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

Outcome measures

Outcome measures
Measure	FMT Capsules, Followed by Placebo Capsules n=25 Participants 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). Analyses included change in outcome measure between baseline and 12 weeks.	Placebo Capsules, Followed by FMT Capsules n=23 Participants Intervention: 25 placebo 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 fecal microbiota transplantation capsules on each of three consecutive days (Day 1, Day 2, Day 3). Analyses included change in outcome measure between baseline and 12 weeks.
Bowel Consistency as Measured by the Bristol Stool Form Scale (BSFS) Week 24	4 score on a scale Standard Deviation 1.0	4 score on a scale Standard Deviation 1.3
Bowel Consistency as Measured by the Bristol Stool Form Scale (BSFS) Baseline	5 score on a scale Standard Deviation 0.8	6 score on a scale Standard Deviation 0.9
Bowel Consistency as Measured by the Bristol Stool Form Scale (BSFS) Week 12	4 score on a scale Standard Deviation 1.0	5 score on a scale Standard Deviation 1.1

SECONDARY outcome

Timeframe: 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.

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.