The primary aim of this phase I/II, randomized, placebo controlled study is the assessment of
safety and tolerability of universal donor FMT compared to placebo in pediatric and young
adult subjects (ages 5 years through 30 years) with active Crohn's colitis (CD) who have
failed, are intolerant to, or have refused traditional first-line maintenance therapy.
Secondary objectives include the identification biomarkers in both donor and recipient that
may confer a clinical response and to establish whether or not ongoing FMT maintenance
therapy is required for maintenance of clinical benefit in pediatric CD.
This is a single-center, phase I/II, randomized, prospective, double-blinded,
placebo-controlled study of FMT in the treatment of active pediatric CD. The primary aim is
to assess safety and feasibility of a weekly FMT maintenance therapy. A total of 60 patients
with active CD (as defined by PCDAI score of >10) will be enrolled and randomized to receive
FMT or placebo-FMT (study treatment) by retention enema for 1 week and oral, frozen
encapsulated inocula/placebo for 7 weeks. After the first 8 weeks, subjects on FMT who
improve or subjects on placebo-FMT who do not improve will have the option to continue on
study treatment or switch to open-label FMT until the end of 4 months from study initiation.
Subjects will be followed by telephone to assess adverse events for a total of 6 months after
their last FMT dose.
An initial subset of 10 subjects will be enrolled in the study (will be limited to only those
patients 12 years of age or older and to those who have mild to moderate Crohn's Disease) and
randomized to receive FMT or placebo. We'd expect short term adverse events to occur within 7
days of FMT administration. Individual subject safety data will be reviewed by the PIto
assess whether FMT appears to be safe in the subject before continuing the subject towards
open-label use of FMT.
Patient metadata and stool samples will be collected at key time points. The patient-reported
metadata collection technique will allow for numerous clinical correlations to be parsed out
using the random forest machine learning capabilities of synthetic learning in microbial
ecology (SLiME) to identify taxonomic features associated with important clinical parameters.
Male and female children and young adults, aged 5 years to 30 years, who meet the following
inclusion criteria, will be enrolled in the study.
An initial subset of 10 subjects will be limited to patients with mild to moderate Crohn's
disease (i.e., PCDAI < 30) and to individuals > 12 years of age. If FMT appears to be safe
in this subset of patients after 8 weeks in the study (to be assessed by a Data Safety
Monitoring Board), expanded enrollment as is described above will occur.
All patients must satisfy below criteria:
1. Have Crohn's colitis (PCDAI >10) and have failed, are intolerant to, or have refused
traditional first-line maintenance therapy.
2. Have had visual or histologic evidence of inflammation confirmed through colonoscopy
no more than 90 days prior to randomization.
3. Have negative test results for Hepatitis B (HBV), Hepatitis C (HCV), and Human
Immunodeficiency Virus (HIV).
4. Have a negative urine hCG test if female of childbearing potential.
5. Able to swallow antibiotic, FMT or placebo capsules.
6. Able to give informed consent and/or assent as appropriate (patients 12-17 will be
asked to provide written assent, patients 5-11 will be observed for assent or dissent
behaviorally, or with verbal/written communication)
7. Willing and able to participate in the study requirements, including serial stool
collection, survey completion and clinic visits.
8. Willing to undergo telephone follow-up to assess for safety and adverse events.
9. Must be free of any known food allergy.
10. Agrees and willing to have an enema for purposes of induction therapy.
Patients who have disease that has required other medications (including steroids,
immunosuppressives, and biologics) will be included.
Subjects who fall into any of the following exclusion criteria at the time of screening are
not eligible for enrollment into the study.
1. Patients with extensive and/or severe CD (i.e. fistulizing disease, abscess, small
bowel obstruction, fevers).
2. Patients in a clinical remission (PCDAI <10).
3. Patients with recent (within 4 weeks) dose change of biologics, 5-ASA, steroids or
4. Patients considered to have toxic megacolon.
5. Patients with a known drug allergy to vancomycin, metronidazole or polymixin.
6. Patients with a history of aspiration, gastroparesis, surgery involving the upper
gastrointestinal tract (that might affect upper gastrointestinal motility) or unable
to swallow pills.
7. Patients with esophageal dysmotility or swallowing dysfunction.
8. Patients with known food allergies.
9. Patients with positive test results for HBV, HCV, or HIV.
10. Female patients with a positive test result on a urine hCG test.
11. Patients unwilling or unable to give consent or participate in all study requirements.
12. Patients unable or unwilling to receive a retention enema for purposes of induction
13. Patients with recent (within 6 weeks) systemic antibiotic use
14. Patients who have testing consistent with active clostridium difficile.
15. Patients with known prior experience with donor FMT
Research personnel and care providers will be educated about inclusion/exclusion criteria
so that only appropriate patients are approached for informed consent. This will reduce the
burden of worry for families and patients as to whether they are suitable candidates for
the study. Subjects who are found to have no evidence of active disease by colonoscopy will
be excluded from the study.