Inflammatory Bowel Disease (IBD)
Conditions
Keywords
ulcerative colitis, gut microbial transplantation
Brief summary
Inflammatory bowel disease (IBD) is a chronic, debilitating, relapsing inflammatory disorder affecting the gastrointestinal tract which does not have a medical cure. IBD consists of 2 different forms: Crohn's Disease (CD) and Ulcerative Colitis (UC). In the last 2 decades, Gut Microbial Transplantation (GMT), also known as fecal transplantation, has been used as a treatment option for Clostridium difficile colitis and UC. The literature supports strong evidence for the plausibility of using GMT for patients with IBD associated colitis, especially for patients with UC. This research will be conducted in the Helen DeVos Children's Hospital (HDVCH) Pediatric gastrointestinal outpatient clinic. A pilot study of ten patients will be conducted to evaluate if GMT improves clinical symptoms in patients with IBD. Patients with IBD colitis (UC and CD with colonic involvement only) will be approached for GMT as a treatment option for their disease. Each subject will undergo 5 sessions (1 session/day, and not necessarily on consecutive days) of GMT within a period of 10 days. Post treatment evaluation will be done at their regularly scheduled clinic follow up. Healthy donors \>18 years of age will be chosen by the family, inclusive of immediate family members and friends. Donors will be required to complete a screening questionnaire, provide medical history, and undergo blood and stool tests.
Interventions
DRUGGut Microbial Transplantation
Each participant received Gut Microbial Transplantation (GMT) as retention enema over a period of 1 hour (60mL enema every 15 minutes) daily for 5 days. Although 240mL of GMT solution was prepared for each participant, the final administered dose was dependent on the subject's comfort and willingness to proceed with the next enema, which was assessed after each enema infusion. Subjects were monitored for 30 minutes after GMT for any immediate adverse events and discharged.
Sponsors
Corewell Health West
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
7 Years to 21 Years
Healthy volunteers
No
Inclusion criteria
Participant Inclusion Criteria: 1. Children ages \>7 and ≤21 years of age with established diagnosis of Inflammatory Bowel Disease (IBD) colitis (patient with ulcerative colitis (UC) or patients with crohn's disease (CD) with colonic involvement only) 2. Have clinical disease (mild to moderate disease: 10≤ Pediatric Ulcerative Colitis Activity Index (PUCAI) \<65) 3. Have stable disease activity and therapy for two months prior to Gut Microbial Transplantation (GMT) procedure. Participant
Exclusion criteria
1. Fulminant colitis 2. Indication or scheduled for surgery 3. Pregnancy 4. Use of probiotic supplements during the study period (subjects who have stopped use of probiotic supplements will be eligible as long as they stop taking it 2 weeks prior to Day 1 of GMT) 5. anemia (hemoglobin \< 6.0 g/dL) in last one month 6. Graft versus host disease (GVHD) 7. Severely immunocompromised - defined as 1. History of opportunistic infection (tuberculosis, Pneumocystis jirovecii or systemic fungal infections) in last one year or 2. Neutropenia: Absolute neutrophil count (ANC) \<500 8. Major intra-abdominal surgery within 90 days prior to Day 1 of GMT 9. Administration of any investigational drug within 30 days prior to Day 1 of GMT. 10. Have received infliximab or other tumor necrosis factor (TNF) inhibitors within 2 months prior to Day 1 of GMT or are expected to receive such therapy within 1 month post final GMT. Donor Inclusion Criteria 1. Based on patient's and parents'/guardian's decision 2. Will be chosen from immediate adult (≥18 years) family members or close friends 3. Should have negative or normal results on screening tests (as explained in donor
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Response | 4 weeks following GMT Treatment | Clinical response (i.e. improvement in Pediatric Ulcerative Colitis Activity Index (PUCAI) score by greater than or equal to 15 points from baseline) at 4 weeks following GMT treatment |
Countries
United States
Participant flow
Recruitment details
An open-label, uncontrolled, single-center, prospective pilot study was conducted at Helen DeVos Children's Hospital's outpatient gastroenterology center. Participants were enrolled between April and December 2012. Each participant took part in the study for 6 weeks. The study was not advertised.
Pre-assignment details
Fifteen patients with ulcerative colitis (UC) were assessed for eligibility; all showed interest in the study. Ten participants met the eligibility criteria and the donors were identified by the participants.
Participants by arm
| Arm | Count |
|---|---|
| Study Participants Ten participants between the ages of 7 to 21 years with mild-to moderate UC (pediatric UC activity index \[PUCAI\] between 15 and 65) were enrolled in the study. PUCAI is a validated tool to measure disease activity in pediatric UC based on clinical symptoms: a score of \<10 = remission; 10-34 = mild disease; 35-64 = moderate disease; 65-85 = severe disease. Participants had stable disease activity and medical treatment for UC for 2 months prior to enrollment. Participants' ongoing treatment for UC was not changed. None of the subjects had concurrent C difficile infection. | 10 |
| Donors Healthy donors (\>18 years of age) were chosen by participants. Donors were required to complete a screening questionnaire, provide medical history, and undergo blood and stool tests. | 10 |
| Total | 20 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Physician Decision | 1 | 0 |
Baseline characteristics
| Characteristic | Study Participants | Donors | Total |
|---|---|---|---|
| Age, Customized | 15.2 Years STANDARD_DEVIATION 4.4 | 39.6 Years STANDARD_DEVIATION 12.7 | 27.4 Years STANDARD_DEVIATION 15.6 |
| Disease Activity before Treatment 0-9: Remission | 0 Participants | 0 Participants | 0 Participants |
| Disease Activity before Treatment 10-34: Mild Disease | 3 Participants | 0 Participants | 3 Participants |
| Disease Activity before Treatment 35-64: Moderate Disease | 7 Participants | 0 Participants | 7 Participants |
| Disease Activity before Treatment 65-85: Severe Disease | 0 Participants | 0 Participants | 0 Participants |
| Disease Extent Extensive | 1 Participants | 0 Participants | 1 Participants |
| Disease Extent Left-sided | 1 Participants | 0 Participants | 1 Participants |
| Disease Extent Pancolitis | 6 Participants | 0 Participants | 6 Participants |
| Disease Extent Proctitis | 2 Participants | 0 Participants | 2 Participants |
| Sex: Female, Male Female | 4 Participants | 4 Participants | 8 Participants |
| Sex: Female, Male Male | 6 Participants | 6 Participants | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 10 / 10 |
| serious Total, serious adverse events | 0 / 10 |
Outcome results
Primary
Clinical Response
Clinical response (i.e. improvement in Pediatric Ulcerative Colitis Activity Index (PUCAI) score by greater than or equal to 15 points from baseline) at 4 weeks following GMT treatment
Time frame: 4 weeks following GMT Treatment
Population: One participant showed intolerance to the treatment (immediate leaking of enema) and was not included in post-treatment disease activity evaluation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Study Participants | Clinical Response | 9 Participants |
Comparison: A power calculation was not done for this pilot study. Changes in PUCAI post-treatment were compared with baseline using the Wilcoxon signed rank test. P value \<0.05 was considered statistically significant.p-value: 0.03Wilcoxon signed rank test