Personalized AZithromycin/metronidAZole, in combination with standard induction therapy, to achieve a fecal microbiome community structure and metagenome changes associated with sustained remission in pediatric Crohn*s Disease (CD): a pilot study

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 20

Inclusion Criteria

1. Provision of signed and dated informed consent form (and assent form, as
applicable)
2. Stated willingness to comply with all study procedures and availability for
the duration of the study
3. Male or female, aged 3 to 17 years
4. Diagnosed with CD according to standard clinical and histological criteria,
within 36 months of week 0
5. Exhibiting mild to moderate symptoms of active disease, as determined by a
PCDAI score >10 (or >7.5 excluding the height item) and <=37.5
6. Evidence of active inflammation based on either: fecal calprotectin level
>=250 microgram/g (local laboratory or pre-arranged sponsor testing) within 30
days prior to week 0 visit; or according to accepted endoscopic and histologic
evidence obtained during an endoscopy procedure completed within 30 days prior
to Week 0 Visit.

Exclusion Criteria

1.Current or previous use of anti-TNF or other biologic therapy
2.Presence of stricturing, penetrating (intestinal or perianal) and/or
fistulizing CD.
3.Pregnancy or lactation
4.Have undergone intestinal resection
5.Laboratory diagnosis of Clostridium Difficile Infection (CDI), if performed
for clinical indication
6.Treatment with another investigational drug or other intervention within 30
days before week 0
7.Risk factors for arrhythmia including history of prolonged QTc, hypokalemia
or hypomagnesemia, resting bradycardia, or concurrent treatment with other
drugs with potential for QT prolongation.
8.History of Cockayne syndrome
9.Prior diagnosis of any hematologic condition/blood dyscrasia which may result
in leukopenia (even if leukocyte count is normal at screening)
10.Known allergy or intolerance to azithromycin or metronidazole
11.Subjects who received IV anti-infective within 35 days prior to week 0 visit
or oral anti-infectives within 14 days prior to the week 0 visit.
12.Subject on oral aminosalicylates who has not been on stable doses for
greater than, or discontinued within, at least 14 days prior to week 0.
13.Subject on cyclosporine, tacrolimus or mycophenolate mofetil. Stable doses
(no change within 14 days prior to week 0) of Azathioprine, 6-mercaptopurine or
MTX are not a reason for exclusion.
14.Subject who received fecal microbial transplantation within 35 days prior to
week 0 visit.
15.Screening laboratory and other analyses show any of the following abnormal
results:
o AST, ALT > 2 X upper limit of the reference range (as determined locally at
each site)
o Urea, Creatinine > 1.5X upper limit of the reference range (as determined
locally at each site)
o White blood cell (WBC) count < 3.0 X 109/L
o Total bilirubin >= 20 micromol/liter (1.17mg/dl); except for subjects with
isolated elevation of indirect bilirubin relating to Gilbert syndrome
o Hemoglobin < 80 gram/liter
o Platelets < 100,000/µL

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Primary Outcome variable: Sustained remission defined as no need of<br /><br>re-induction for clinical flare (new course of nutritional therapy, need to<br /><br>start steroids), steroid dependence, biologic (anti-TNF) use, and/or intestinal<br /><br>surgery by 12 months.</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>Secondary Outcome variables: Longitudinal (clustered and with respect to<br /><br>baseline) changes in disease activity indices (PCDAI: 0-100) components and<br /><br>inflammatory markers in stool and blood at each study visit up to 12 months.<br /><br>Longitudinal (clustered and with respect to baseline) changes in<br /><br>patient-reported outcomes (PRO) by 12 months.<br /><br>Exploratory Outcome variable: Longitudinal (clustered and with respect to<br /><br>baseline) changes in fecal microbiome taxonomic composition or in total gene<br /><br>(metagenome) content. The changes will be analyzed for association with<br /><br>changes in disease activity (e.g. relapse or sustained remission) over time up<br /><br>to 12 months.</p><br>