Crohn Disease Clinical Trial
— PAZAZOfficial title:
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
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.
Status | Recruiting |
Enrollment | 20 |
Est. completion date | December 2023 |
Est. primary completion date | December 2023 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 3 Years to 17 Years |
Eligibility | 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. Fecal calprotectin level >=250 µg/g within 30 days prior to week 0 visit based on local measurement, if available, or to be arranged with lead site if an endoscopy is not performed within 30 days prior to week 0 visit. Exclusion Criteria: 1. Current or previous use of biologic therapy; 2. Presence of stricturing, penetrating (intestinal or perianal) and/or fistulizing CD; 3. Pregnancy or lactation; 4. Have undergone intestinal resection; 5. Positive Clostridium Difficile toxin; 6. Treatment with another investigational drug or other intervention within 30 days before week 0; 7. Risk factors for arrhythmia including history of prolonged corrected QT interval (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 intravenous anti-infective within 35 days prior to week 0 visit or 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 methotrexate (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: - aspartate transaminase (AST), alanine transaminase (ALT) > 2 X upper limit of the reference range, - White blood cell (WBC) count < 3.0 X 109/L, - Total bilirubin >= 20 micromol/liter (1.17 mg/dL); except for subjects with isolated elevation of indirect bilirubin relating to Gilbert syndrome, - Estimated glomerular filtration rate (GFR) by simplified 4-variable Modification of Diet in Renal Disease (MDRD) formula of < 30 mL/min/1.73 m², - Hemoglobin < 80 gram/liter, - Platelets < 100,000/µL. |
Country | Name | City | State |
---|---|---|---|
Canada | IWK Health Centre | Halifax | |
Israel | Wolfson Medical Centre | Tel Aviv | |
Netherlands | Amsterdam UMC | Amsterdam | |
United States | University of Pittsburgh Medical Center, Children's Hospital of Pittsburgh | Pittsburgh | Pennsylvania |
United States | UCSF Benioff Children's Hospital | San Francisco | California |
Lead Sponsor | Collaborator |
---|---|
University of North Carolina, Chapel Hill | Crohn's and Colitis Foundation, University of Amsterdam |
United States, Canada, Israel, Netherlands,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Percent of Subjects with Sustained Remission | Subjects 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 | Week 52 | |
Primary | Feasibility of multinational microbiome-randomized trial | Proportion of subjects that are successfully randomized in randomization procedure, proportion of patients per treatment arm, proportion of subjects that complete 1 year endpoint | week 52 | |
Secondary | Change in Pediatric Crohn's Disease Activity Index (PCDAI) Score over Baseline to 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. | Baseline to Week 52 | |
Secondary | Change in Fecal Calprotectin Levels in Stool over Baseline to Week 52 | Fecal calprotectin is a non-invasive surrogate protein marker for bowel inflammation. | Baseline to Week 52 | |
Secondary | Change in C-Reactive Protein (CRP) Levels in Blood over Baseline to 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. | Baseline to Week 52 | |
Secondary | Change in IMPACT-III Score over Baseline to 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, subjects aged 9 and older will complete this questionnaire at week 0, 12, 24, and 52. Subjects 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. | Baseline to Week 52 |
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