Pilot Study of Fundamental Modification of the Gut Microbiota in the Treatment of Refractory Crohn's Disease
Condition: Crohn Disease
MeSH terms: Crohn Disease
Intervention: Vancomycin; Neomycin; Ciprofloxacin; Polyethylene Glycol 3350; Fluconazole
Intervention description: Oral suspension 4 times daily (Day 1-14); Oral three times daily (Days 1-3); Oral twice daily (Days 4-14); Dissolved in Gatorade on day 2; Orally once daily (Day 1-14)
Intervention MeSH terms: Vancomycin; Ciprofloxacin; Neomycin; Fluconazole; Polyethylene glycol 3350
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 10.0
Sex: All
Minimum age: 6 Years
Healthy volunteers: No

Summary:

      The purpose of this study is to determine the effect of a novel gut microbiota-targeted
      therapeutic regimen (bowel lavage and antibiotics with or without an antifungal) in the
      management of active Crohn's Disease (CD) or indeterminate colitis (IBDU) that is refractory
      to conventional, immunosuppressive therapy. In addition, the study will determine the effect
      of PEG lavage alone on fecal calprotectin and gut microbiota in patients who are undergoing a
      PEG lavage for clinical care.
    

Eligibility criteria:

        Group 1

        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 or IBDU 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

        Group 2

        Inclusion Criteria

          -  Males or females 10 years of age and older.

          -  Patients undergoing a clinical GI endoscopy due to suspicion for active intestinal
             inflammation determined by physician global assessment (PGA).

          -  Undergoing a bowel preparation as part of clinical care.

          -  Parental/guardian permission (informed consent) and if appropriate, child assent.

        Exclusion Criteria

          -  Antibiotic use within the past 30 days.

          -  Current presence of an ostomy bag.

          -  Patients undergoing a non- polyethylene glycol 3350 cleanout.

          -  Unwillingness to provide informed consent.

          -  Parents/guardians or subjects who, in the opinion of the Investigator, may be
             non-compliant with study schedules or procedures.