Pilot Study of Fundamental Modification of the Gut Microbiota in the Treatment of Refractory Crohn's Disease

Investigators will evaluate the efficacy of a novel treatment regimen, employing
non-immunosuppressive medications, in the management of refractory CD. Refractory patients
include those patients who have experienced loss of responsiveness (LOR) or primary
nonresponse to an immunomodulator or a biologic. Investigators will treat participants with a
combination of gut microbiota-targeted therapies to restore a healthy gut microbiome
composition. Investigators believe that this strategy will both treat the gut inflammation
associated with inflammatory bowel disease (IBD) as well as salvage response to immune
suppressive therapies.

Inclusion Criteria:

- Males or females 6-18 years of age

- Current weight >10 kg (or 22 lb)

- Ability to swallow pills

- Normal kidney function

- Normal Aspartate transaminase (AST), Alanine transaminase (ALT), and alkaline
phosphatase

- Active CD defined as PCDAI ≥ 30

- C-Reactive Protein (CRP) ≥ 15mg/L (or 1.5mg/dL) or fecal calprotectin (FCP)>350mcg/g
(within one month of enrollment)

- Have been treated with one of the following therapies for at least 8 weeks with
primary nonresponse or an initial response, followed by loss of response [LOR]
(self-reported worsening of symptoms for ≥ 7 days): azathioprine, 6-mercaptopurine,
methotrexate, adalimumab, certolizumab, golimumab, infliximab, natalizumab,
vedolizumab, or ustekinumab **These medications must have been administered at
standard, therapeutic dosages.

Exclusion Criteria:

- Known allergy or intolerance to aminoglycosides or any of the medications used in this
study

- Current use of one or more of the following medications: 5-fluorouracil, digoxin,
anticoagulants, theophylline, phenytoin, probenecid, duloxetine, clozapine,
sildenafil, hydrochlorothiazide, cyclosporine, hypoglycemics, terfenadine, tacrolimus,
rifabutin, midazolam, and voriconazole

- Known diagnosis of diabetes mellitus

- Known or suspected structuring disease producing obstructive symptoms

- Active Clostridium difficile infection

- Prolonged QTc interval as seen on enrollment EKG

- Current use of antibiotics

- Starting or increasing the dose of an IBD related medication within 4 weeks of
screening