Pouchitis, Ulcerative Colitis
Conditions
Keywords
FMT
Brief summary
The aim of our study is to investigate the efficacy and safety of fecal microbiota transplantation (FMT) in the treatment of antibiotic dependent chronic pouchitis. This is a double-blinded randomized placebo controlled study. 13 patients receive a fecal transplantation from the healthy tested donor and 13 patients in the control group receive their own feces.
Detailed description
Pouchitis is the most common long term complication among patients with ulcerative colitis who have undergone restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA). The etiology of pouchitis remains unclear. There is significant clinical evidence implicating bacteria in the pathogenesis. It has been shown that fecal microbiota transplantation (FMT) is an effective treatment for recurrent Clostridium difficile -infection. Case reports have also shown promising results of FMT in patients with inflammatory bowel disease. Currently there is no established effective treatment for chronic antibiotic dependent or refractory pouchitis. The aim of our study is to investigate the efficacy and safety of fecal transplantation in the treatment of chronic pouchitis instead of antibiotic therapy. Another aim is to evaluate phylogenetic analysis of the fecal microbiota trying to find microorganisms contributing to good results in fecal transplantation in IPAA patients. Patients receive FMTs on weeks 0 and 4. Antibiotic treatment has been stopped 36 hours before the first FMT.
Interventions
BIOLOGICALFecal microbiota transplantation
Follow up of the patients include a telephone call after 12 and 26 weeks after the FMT, and a clinical control visit 52 weeks after the transplantation. The clinical part of the Pouchitis Disease Activity Index score is assessed during each call and clinical visit. Fecal stool samples for phylogenetic analysis are collected before FMT and on weeks 4, 12, 26, and 52.
BIOLOGICALPlacebo
Follow up of the patients include a telephone call after 12 and 26 weeks after the FMT, and a clinical control visit 52 weeks after the transplantation. The clinical part of the Pouchitis Disease Activity Index score is assessed during each call and clinical visit. Fecal stool samples for phylogenetic analysis are collected before FMT and on weeks 4, 12, 26, and 52.
Sponsors
Helsinki University Central Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Status post of restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) for ulcerative colitis * Pouchitis diagnosed by the symptoms and by endoscopy including histology within 6 months prior to FMT * Need of frequent or continuous use of antibiotics or probiotics because of the chronic pouchitis * Availability of consecutive fecal samples during one year * Compliance to attend FMT and control pouchoscopy after 52 weeks
Exclusion criteria
* Unable to provide informed consent * Use of immunosuppressive or biological medication * Use of corticosteroids * Acute pouchitis * Pregnancy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Remission | 52 weeks | Clinical remission at week 52. All criteria need to be met: Pouchitis Disease Activity Index \<7 and no need for antibiotic treatment for pouchitis during the follow up |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Evaluation of the Changes in Gut Microbiota | 54 weeks | Fecal stool samples for phylogenetic analysis are collected before FMT and on weeks 4, 12, 26, and 52. |
Countries
Finland
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Donors Feces Fecal microbiota transplantation is performed by experienced endoscopists through flexible sigmoideoscopy into the afferent limb. The second FMT is installed via catheter into the pouch 4 weeks after the first FMT.
Fecal microbiota transplantation: Follow up of the patients include a telephone call after 12 and 26 weeks after the FMT, and a clinical control visit 52 weeks after the transplantation. The clinical part of the Pouchitis Disease Activity Index score is assessed during each call and clinical visit. Fecal stool samples for phylogenetic analysis are collected before FMT and on weeks 4, 12, 26, and 52. | 13 |
| Patients Own Feces Fecal microbiota transplantation is performed by experienced endoscopists through flexible sigmoideoscopy into the afferent limb. The second FMT is installed via catheter into the pouch 4 weeks after the first FMT.
Placebo: Follow up of the patients include a telephone call after 12 and 26 weeks after the FMT, and a clinical control visit 52 weeks after the transplantation. The clinical part of the Pouchitis Disease Activity Index score is assessed during each call and clinical visit. Fecal stool samples for phylogenetic analysis are collected before FMT and on weeks 4, 12, 26, and 52. | 13 |
| Total | 26 |
Baseline characteristics
| Characteristic | Donors Feces | Patients Own Feces | Total |
|---|---|---|---|
| Age, Continuous | 42.7 years STANDARD_DEVIATION 10.2 | 45.5 years STANDARD_DEVIATION 11.7 | 44.1 years STANDARD_DEVIATION 10.9 |
| Antibiotic use at time of study enrollment continuous use | 5 Participants | 7 Participants | 12 Participants |
| Antibiotic use at time of study enrollment repeated | 8 Participants | 6 Participants | 14 Participants |
| Probiotics | 5 Participants | 6 Participants | 11 Participants |
| Race and Ethnicity Not Collected | — | — | 0 Participants |
| Region of Enrollment Finland | 13 participants | 13 participants | 26 participants |
| Sex: Female, Male Female | 6 Participants | 5 Participants | 11 Participants |
| Sex: Female, Male Male | 7 Participants | 8 Participants | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 13 | 0 / 13 |
| other Total, other adverse events | 3 / 13 | 1 / 13 |
| serious Total, serious adverse events | 0 / 13 | 0 / 13 |
Outcome results
Primary
Clinical Remission
Clinical remission at week 52. All criteria need to be met: Pouchitis Disease Activity Index \<7 and no need for antibiotic treatment for pouchitis during the follow up
Time frame: 52 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Donors Feces | Clinical Remission | 4 Participants |
| Patients Own Feces | Clinical Remission | 5 Participants |
Comparison: The sample size (n = 26) was calculated according to the estimation that the remission rate in the FMT group would be 80% and 25% in the placebo group during the follow-up of 1 year. This difference of 55% was considered to be clinically meaningful. The significance level was selected to be 1%, and the power was set to 90%.p-value: 0.183Log Rank
Secondary
Evaluation of the Changes in Gut Microbiota
Fecal stool samples for phylogenetic analysis are collected before FMT and on weeks 4, 12, 26, and 52.
Time frame: 54 weeks