This is a multi-center, randomized, controlled open-label add-on design trial pilot study to evaluate the efficacy of personalized adjunctive antibiotic (azithromycin + metronidazole) therapy in pediatric subjects with mild to moderate Crohn's disease (CD) who have a microbiome profile associated with increased risk of early relapse. This an add-on design trial for subjects already receiving standard of care therapy to induce remission; there will be no placebos.
The study hypothesis is that adjunctive antibiotic therapy will improve clinical response to standard of care (SOC) induction therapy in a subgroup of CD patients with a relapse-associated microbiome profile. Prior to starting SOC induction therapy at week 0, subjects will provide a baseline stool sample that will be screened for microbiome profiles associated with risk of relapse according to an established statistical model. At week 4, subjects with a relapse-associated microbiome will be randomized into either a control arm that will continue to receive SOC induction therapy for an additional 8 weeks, or a treatment arm that will receive adjunctive antibiotic therapy in addition to continuing to receive SOC induction therapy for an additional 8 weeks. Subjects who do not have a relapse-associated microbiome will enter a separate control arm that will continue to receive SOC induction therapy and will have data collected for exploratory objectives. Subjects who are not in clinical remission by week 4 will receive antibiotic therapy regardless of microbiome signature at baseline. Subjects will be monitored for an additional 40 weeks after the treatment period (52 weeks total).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
13
Weeks 4-12: 7.5 mg/kg azithromycin once daily (500 mg/day maximum) for five consecutive days/ week for 4 weeks, and 3 times a week for the following 4 weeks
Weeks 4-12: 20 mg/kg/day of metronidazole (10 mg/kg twice daily to a maximum of 1000 mg/day) for 8 weeks
SOC induction therapy is nutritional therapy (Crohn's disease exclusion diet + partial enteral nutrition) for up to 12 weeks. Induction therapy is as assigned by the treating gastroenterologist prior to study entry.
UCSF Benioff Children's Hospital
San Francisco, California, United States
University of Pittsburgh Medical Center, Children's Hospital of Pittsburgh
Pittsburgh, Pennsylvania, United States
IWK Health Centre
Halifax, Canada
Wolfson Medical Centre
Tel Aviv, Israel
Number of Participants With Sustained Remission
Participants stratified based on carriage of an at-risk microbiome without need for re-induction for clinical flare (new course of nutritional therapy, need to restart steroids), steroid dependence, biologic (e.g. anti-TNF) use, and/or intestinal surgery.
Time frame: Week 52
Feasibility of Multinational Microbiome-randomized Trial
The number of participants with microbiome data available at Week 4/5.
Time frame: Week 4/5
Number of Participants With Normal Pediatric Crohn's Disease Activity Index (PCDAI) Score at Week 52
Pediatric Crohn's Disease Activity Index (PCDAI) is an index used to measure disease activity of pediatric patients with Crohn's Disease assessing abdominal pain, stool frequency, patient functioning, hematocrit, erythrocyte sedimentation rate, albumin, weight, height, examination of abdomen, perirectal disease, and extraintestinal manifestations. Scores range from 0 to 100, with higher scores indicating greater disease activity.
Time frame: Week 52
Number of Participants With Normal Fecal Calprotectin Levels in Stool at Week 52
Fecal calprotectin is a non-invasive surrogate protein marker for bowel inflammation. The normal range is \<200 mcg/g.
Time frame: Week 52
Number of Participants With Normal C-Reactive Protein (CRP) Levels in Blood at Week 52
CRP is a blood protein marker of inflammation. CRP levels are classified as 'normal/low' or 'elevated/high' based on standard laboratory reference ranges.
Time frame: Week 52
IMPACT-III Score at Week 52
The IMPACT III questionnaire is a 35-item assessment of health-related quality of life in patients with inflammatory bowel disease (Crohn's disease \[CD\] or ulcerative colitis). In this study, participants aged 9 and older will complete this questionnaire at week 0, 12, 24, and 52. Participants mark an option from 1 to 5 for each item.The total scores range from 35 to 175, with higher scores representing a better quality of life.
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Amsterdam UMC
Amsterdam, Netherlands
Time frame: Week 52