Crohn's Disease
Conditions
Keywords
Prevention, Recurrence, Fecal Microbiota Therapy
Brief summary
The objective of this trial is to assess if Fecal Microbiota Therapy (FMT) can reduce the risk of endoscopic recurrence of Crohn's disease (CD) in patients after intestinal resection. The specific outcomes of FMT to be examined are: 1) endoscopic appearance, 2) clinical symptoms, 3) safety and tolerability, and 4) microbial diversity. The research team hypothesizes that FMT will prevent establishment of pro-inflammatory microbiome after surgery, leading to a reduced probability of recurrence of macroscopic inflammation. It is also hypothesized that FMT will be safe and well-tolerated in these patients.
Interventions
BIOLOGICALFecal Microbiota Transplant (FMT)
Fecal Microbiota Transplant (FMT)
Sponsors
Brigham and Women's Hospital
Beth Israel Deaconess Medical Center
Massachusetts Institute of Technology
Boston Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
(Patients): * Adults (age \> 18) * Confirmed diagnosis of Crohn's disease (CD), based on endoscopy, histology and imaging (confirmed by Study PI for each site) * Ileo-cecal resection or terminal ileal resection for CD within 30 days prior to enrollment * Resection margins & anastomosis free of active inflammation based on histology and surgical description (confirmed by Study PI for each site) * No therapy to prevent post-operative recurrence of CD. A 30-day wash-out period for anti- tumor necrosis factors (TNF)s, thiopurines, antibiotics will be required prior to enrollment.
Exclusion criteria
(Patients): * Diagnosis of indeterminate colitis * Women who are pregnant or nursing * Patients who are unable to give informed consent * Patients who are unable or unwilling to undergo colonoscopy with moderate sedation (\>ASA class II) * Patients who have previously undergone FMT * Patients who have a confirmed malignancy or cancer * Participation in a clinical trial in the preceding 30 days or simultaneously during this trial * Probiotic use within 30 days of start date * Decompensated cirrhosis * Congenital or acquired immunodeficiencies * Chronic kidney disease as defined by a GFR \<60mL/min/1.73m2 44 * History of rheumatic heart disease, endocarditis, or valvular disease due to risk of bacteremia from colonoscopy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Post-operative Endoscopic Recurrence | within 6 months of ileo-cecal resection | Percentage of patients in each arm of the trial who develop endoscopic recurrence within 6 months of ileo-cecal resection. Endoscopic recurrence will be defined as a Rutgeert's score of greater than i2 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Microbial Diversity: Shannon Diversity Index | baseline, 4, 12, and 26 weeks | The Shannon Diversity Index is a measure of entropy and is a function of the distribution of the total number of organisms across all of the species. If S is the total number of species in the sample and p\_i is the number of organisms in the i-th species divided by the total number of organisms, then Diversity = -Σ p\_i log(p\_i). Lower values indicate more diversity while higher values indicate less diversity. |
| Number of Participants in Clinical Remission at 26 Weeks | 26 weeks | Clinical remission is defined as having a Harvey Bradshaw Index (HBI) score \<5 at week 26. The HBI can range from 0 to 18 and higher scores are associated with more severe disease. |
| Adverse Events Frequency | 4, 12, and 26 weeks | Number of participants with adverse events |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Fecal Microbiota Transplant (FMT) Fecal Microbiota Transplant (FMT) via colonoscopy
Fecal Microbiota Transplant (FMT): Fecal Microbiota Transplant (FMT) | 15 |
| Control No Fecal Microbiota Transplant (FMT) via colonoscopy | 9 |
| Total | 24 |
Baseline characteristics
| Characteristic | Total | Control | Fecal Microbiota Transplant (FMT) |
|---|---|---|---|
| Age, Continuous | 41 years STANDARD_DEVIATION 6 | 46 years STANDARD_DEVIATION 6 | 39 years STANDARD_DEVIATION 7 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 24 Participants | 9 Participants | 15 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Montreal B3 classification | 6 Participants | 2 Participants | 4 Participants |
| Prior resection | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 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 | 24 Participants | 9 Participants | 15 Participants |
| Region of Enrollment United States | 24 participants | 9 participants | 15 participants |
| Sex: Female, Male Female | 16 Participants | 6 Participants | 10 Participants |
| Sex: Female, Male Male | 8 Participants | 3 Participants | 5 Participants |
| Smoker | 1 Participants | 0 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 15 | 0 / 9 |
| other Total, other adverse events | 11 / 15 | 6 / 9 |
| serious Total, serious adverse events | 0 / 15 | 1 / 9 |
Outcome results
Primary
Post-operative Endoscopic Recurrence
Percentage of patients in each arm of the trial who develop endoscopic recurrence within 6 months of ileo-cecal resection. Endoscopic recurrence will be defined as a Rutgeert's score of greater than i2
Time frame: within 6 months of ileo-cecal resection
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Fecal Microbiota Transplant (FMT) | Post-operative Endoscopic Recurrence | 20 percentage of participants |
| Control | Post-operative Endoscopic Recurrence | 0 percentage of participants |
Secondary
Adverse Events Frequency
Number of participants with adverse events
Time frame: 4, 12, and 26 weeks
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Fecal Microbiota Transplant (FMT) | Adverse Events Frequency | 4 weeks | 2 Participants |
| Fecal Microbiota Transplant (FMT) | Adverse Events Frequency | 26 weeks | 0 Participants |
| Fecal Microbiota Transplant (FMT) | Adverse Events Frequency | 12 weeks | 0 Participants |
| Control | Adverse Events Frequency | 12 weeks | 2 Participants |
| Control | Adverse Events Frequency | 26 weeks | 3 Participants |
| Control | Adverse Events Frequency | 4 weeks | 1 Participants |
Secondary
Change in Microbial Diversity: Shannon Diversity Index
The Shannon Diversity Index is a measure of entropy and is a function of the distribution of the total number of organisms across all of the species. If S is the total number of species in the sample and p\_i is the number of organisms in the i-th species divided by the total number of organisms, then Diversity = -Σ p\_i log(p\_i). Lower values indicate more diversity while higher values indicate less diversity.
Time frame: baseline, 4, 12, and 26 weeks
Population: There was insufficient data collected for any of the timeframes to calculate the Shannon Diversity Index.
| Arm | Measure | Group | Value |
|---|---|---|---|
| Unknown | Change in Microbial Diversity: Shannon Diversity Index | 4 weeks | — |
| Unknown | Change in Microbial Diversity: Shannon Diversity Index | 12 weeks | — |
| Unknown | Change in Microbial Diversity: Shannon Diversity Index | 26 weeks | — |
Secondary
Number of Participants in Clinical Remission at 26 Weeks
Clinical remission is defined as having a Harvey Bradshaw Index (HBI) score \<5 at week 26. The HBI can range from 0 to 18 and higher scores are associated with more severe disease.
Time frame: 26 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Fecal Microbiota Transplant (FMT) | Number of Participants in Clinical Remission at 26 Weeks | 14 Participants |
| Control | Number of Participants in Clinical Remission at 26 Weeks | 5 Participants |