Summary

Eligibility
for people ages 3-17 (full criteria)
Location
at San Francisco, California and other locations
Dates
study started
estimated completion

Description

Summary

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.

Official 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

Details

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).

Keywords

Crohn Disease Pediatric Crohns Disease Microbiome Azithromycin Metronidazole

Eligibility

You can join if…

Open to people ages 3-17

  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.

You CAN'T join if...

  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:
  16. aspartate transaminase (AST), alanine transaminase (ALT) > 2 X upper limit of the reference range,
  17. White blood cell (WBC) count < 3.0 X 109/L,
  18. Total bilirubin >= 20 micromol/liter (1.17 mg/dL); except for subjects with isolated elevation of indirect bilirubin relating to Gilbert syndrome,
  19. Estimated glomerular filtration rate (GFR) by simplified 4-variable Modification of Diet in Renal Disease (MDRD) formula of < 30 mL/min/1.73 m²,
  20. Hemoglobin < 80 gram/liter,
  21. Platelets < 100,000/µL.

Locations

  • UCSF Benioff Children's Hospital
    San Francisco California 94158 United States
  • Children's Hospital Pittsburgh
    Pittsburgh Pennsylvania 15224 United States

Details

Status
not yet accepting patients
Start Date
Completion Date
(estimated)
Sponsor
University of North Carolina, Chapel Hill
ID
NCT04186247
Phase
Phase 2
Study Type
Interventional
Last Updated