Crohn's Disease (CD), Inflammatory Bowel Diseases (IBD), Ulcerative Colitis (UC)
Conditions
Keywords
Inflammatory Bowel Diseases (IBD), Crohn's Disease (CD), Ulcerative Colitis (UC)
Brief summary
A disturbance in the diversity of gut bacterial composition could be linked to several immune mediated diseases including inflammatory bowel diseases (IBD). IBD can be classified into Crohn's Disease (CD) and Ulcerative Colitis (UC). Both these diseases occur from abnormal immune reaction to resident gut bacteria.The process of fecal microbiota transplantation (FMT) where fecal bacteria from a healthy individual is transferred into a recipient, has recently received attention as an alternative therapy for individuals affected with these life-altering diseases. In this study, the investigators will perform fecal transplantation on the subjects meeting inclusion criteria, to determine the efficacy and safety of this therapy in subjects with IBD (CD and UC) who are not responding to first line therapy, and are in a flare.
Detailed description
50 subjects (25 subjects with Crohn's Disease and 25 subjects with Ulcerative Colitis) who are 2 to 22 years of age will be enrolled in the trial over 3 years. The fecal donors, preferably a parent or sibling, will be extensively screened for infectious diseases prior to providing stool for the transplant. Patients who are failing primary therapy, are in a flare, and require restaging of their IBD by an endoscopy and colonoscopy will be approached for the study. Standard of care endoscopy and colonoscopy will be performed on each subject and 2 additional biopsies will be taken for analysis. Microbiota analysis will also be performed on both the donor and recipient stool sample prior to transplantation, and on the recipient sample at 1 week, 1 month, and 6 months post transplantation. The primary objective will be to study the safety of FMT in all enrolled subjects. The study will also correlate efficacy and patient outcomes with the fecal microbiome prior to, and after FMT. The secondary objectives are to examine the efficacy of FMT in the treatment of children with IBD using the Pediatric Ulcerative Colitis Activity Index (PUCAI) and the Pediatric Crohn Disease Activity Index (PCDAI) analysis. Correlate the patient outcomes with the fecal microbiome prior to, and after FMT.
Interventions
BIOLOGICALFecal Microbiota Transplantation (FMT)
The process of fecal microbiota transplantation (FMT), where fecal bacteria from a healthy individual is transferred into a recipient as an alternative therapy for individuals affected with these life-altering diseases: Crohn's Disease (CD), and/or Ulcerative Colitis (UC).
Sponsors
University of Pittsburgh
Stanford University
Children's Mercy Hospital Kansas City
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
2 Years to 22 Years
Healthy volunteers
Yes
Inclusion criteria
STUDY SUBJECT INCLUSION CRITERIA: Current IBD patients who have: * UC patients with a flare due to failure of current therapy and have to undergo esophagogastroduodenoscopy (EGD) and colonoscopy for restaging the disease and escalation of therapy. * CD patients with ileo colonic or colonic disease who require an EGD and colonoscopy for disease assessment due to a flare or poor control. * The ability to safely undergo colonoscopy (physical status classification used by the American Society of Anesthesiologists). * PUCAI score less than sixty five. * PCDAI score less than forty. STUDY SUBJECTS
Exclusion criteria
* Patients with Crohn's disease: complications like an abscess, phlegmon, stricture, small bowel obstruction, perforation, internal or external fistulization or infection as causes for flare up before being deemed eligible for recruitment to the study. We will check for these complications if a recent study has not been done. * Severe immunosuppression: Biologicals with concomitant steroids (\>30 mg/day). * Central Line. * Pressor or ventilatory support. * On antibiotics. * Patients with Crohn's disease found to have complications like an abscess, phlegmon, stricture, small bowel obstruction, perforation, internal or external fistulization or infection. * Not willing to consent or follow guidelines throughout research trial. * Screening labs in either donor or recipient reveal problems with performing fecal microbiome transplantation because inclusion requirements are no longer met. * Physician discretion. * Participant request. DONOR
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Occurrences of Adverse Events at 6 Months According to Adverse Event Term | 6 months | Adverse events recorded to determine safety of Fecal Microbiome Transplant in the treatment of children with IBD. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Examine the Efficacy of Fecal Microbiome Transplant in the Treatment of Children With IBD Using the Pediatric Ulcerative Colitis Activity Index (PUCAI) and the Pediatric Crohn Disease Activity Index (PCDAI) Analysis. | Baseline, Day 30, Day 180 | Efficacy outcomes scored via Pediatric Ulcerative Colitis Activity Index (PUCAI) and the Pediatric Crohn Disease Activity Index (PCDAI) analysis. Scored at baseline, day 30, and at day 180 for responders. The PUCAI score range is 0-85, where the higher the number the more severe the disease (A score of 65 and up is considered severe, a score of 35-64 is considered moderate, and a score of 10-34 is considered mild). The PUCAI is the scoring system used for patients with ulcerative colitis/indeterminate colitis. The PCDAI score range is 0-100, where the higher the number the more severe the disease (A score of greater than 30 is considered moderate to severe, a score of 11-30 is considered mild, and a score of 10 or less is considered inactive disease). The PCDAI is the scoring system used for patients with crohn's disease. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Fecal Microbiome Transplantation Use of Fecal Microbiome Transplantation for participants with IBD. | 23 |
| Total | 23 |
Baseline characteristics
| Characteristic | Fecal Microbiome Transplantation |
|---|---|
| Age, Categorical <=18 years | 19 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 4 Participants |
| Age, Continuous | 10 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 20 Participants |
| Region of Enrollment United States | 23 Participants |
| Sex: Female, Male Female | 11 Participants |
| Sex: Female, Male Male | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 23 |
| other Total, other adverse events | 12 / 23 |
| serious Total, serious adverse events | 0 / 23 |
Outcome results
Primary
Number of Occurrences of Adverse Events at 6 Months According to Adverse Event Term
Adverse events recorded to determine safety of Fecal Microbiome Transplant in the treatment of children with IBD.
Time frame: 6 months
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Overall Study | Number of Occurrences of Adverse Events at 6 Months According to Adverse Event Term | Moderate Abdominal Pain | 11 Events |
| Overall Study | Number of Occurrences of Adverse Events at 6 Months According to Adverse Event Term | Diarrhea | 5 Events |
| Overall Study | Number of Occurrences of Adverse Events at 6 Months According to Adverse Event Term | Flatulence and Bloating | 5 Events |
| Overall Study | Number of Occurrences of Adverse Events at 6 Months According to Adverse Event Term | Emesis | 3 Events |
| Overall Study | Number of Occurrences of Adverse Events at 6 Months According to Adverse Event Term | Bloody Stools | 2 Events |
| Overall Study | Number of Occurrences of Adverse Events at 6 Months According to Adverse Event Term | Nausea | 2 Events |
| Overall Study | Number of Occurrences of Adverse Events at 6 Months According to Adverse Event Term | Fever | 1 Events |
Secondary
Examine the Efficacy of Fecal Microbiome Transplant in the Treatment of Children With IBD Using the Pediatric Ulcerative Colitis Activity Index (PUCAI) and the Pediatric Crohn Disease Activity Index (PCDAI) Analysis.
Efficacy outcomes scored via Pediatric Ulcerative Colitis Activity Index (PUCAI) and the Pediatric Crohn Disease Activity Index (PCDAI) analysis. Scored at baseline, day 30, and at day 180 for responders. The PUCAI score range is 0-85, where the higher the number the more severe the disease (A score of 65 and up is considered severe, a score of 35-64 is considered moderate, and a score of 10-34 is considered mild). The PUCAI is the scoring system used for patients with ulcerative colitis/indeterminate colitis. The PCDAI score range is 0-100, where the higher the number the more severe the disease (A score of greater than 30 is considered moderate to severe, a score of 11-30 is considered mild, and a score of 10 or less is considered inactive disease). The PCDAI is the scoring system used for patients with crohn's disease.
Time frame: Baseline, Day 30, Day 180
Population: Only participants that responded to treatment
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Overall Study | Examine the Efficacy of Fecal Microbiome Transplant in the Treatment of Children With IBD Using the Pediatric Ulcerative Colitis Activity Index (PUCAI) and the Pediatric Crohn Disease Activity Index (PCDAI) Analysis. | Baseline | 40 score on a scale |
| Overall Study | Examine the Efficacy of Fecal Microbiome Transplant in the Treatment of Children With IBD Using the Pediatric Ulcerative Colitis Activity Index (PUCAI) and the Pediatric Crohn Disease Activity Index (PCDAI) Analysis. | Day 30 in responders | 11.6 score on a scale |
| Overall Study | Examine the Efficacy of Fecal Microbiome Transplant in the Treatment of Children With IBD Using the Pediatric Ulcerative Colitis Activity Index (PUCAI) and the Pediatric Crohn Disease Activity Index (PCDAI) Analysis. | Day 180 in responders | 21.6 score on a scale |
| Fecal Microbiome Transplantation With Crohn's Disease | Examine the Efficacy of Fecal Microbiome Transplant in the Treatment of Children With IBD Using the Pediatric Ulcerative Colitis Activity Index (PUCAI) and the Pediatric Crohn Disease Activity Index (PCDAI) Analysis. | Baseline | 11.6 score on a scale |
| Fecal Microbiome Transplantation With Crohn's Disease | Examine the Efficacy of Fecal Microbiome Transplant in the Treatment of Children With IBD Using the Pediatric Ulcerative Colitis Activity Index (PUCAI) and the Pediatric Crohn Disease Activity Index (PCDAI) Analysis. | Day 30 in responders | 1.6 score on a scale |
| Fecal Microbiome Transplantation With Crohn's Disease | Examine the Efficacy of Fecal Microbiome Transplant in the Treatment of Children With IBD Using the Pediatric Ulcerative Colitis Activity Index (PUCAI) and the Pediatric Crohn Disease Activity Index (PCDAI) Analysis. | Day 180 in responders | 0 score on a scale |