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
- Conditions
- Crohn's Disease
- Registration Number
- NL-OMON24884
- Lead Sponsor
- Amsterdam UMC, location AMC
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Pending
- Sex
- Not specified
- Target Recruitment
- 20
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.
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/µ
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method - To evaluate the feasibility of a multicenter trial on different continents with treatment allocation at week 4 depending on stool sample results at baseline<br>- To evaluate the potential efficacy of personalized adjunctive antibiotic therapy in maintaining clinical remission in pediatric subjects undergoing SOC induction therapy for mild to moderate Crohn’s disease who have a relapse-associated microbiome profile
- Secondary Outcome Measures
Name Time Method - To evaluate the potential efficacy of personalized adjunctive antibiotic therapy in improving PRO, components of established disease activity measures in remission, as well as ‘biochemical’ remission in pediatric subjects undergoing SOC induction therapy for mild to moderate Crohn’s disease who have a relapse-associated microbiome profile<br>- To investigate relationship between changes in subject microbiome composition and changes in disease activity over time.