The Vitamin D in Pediatric Crohn's Disease
Condition: Crohn's Disease
MeSH terms: Crohn Disease
Study type: Interventional
Phase: Phase 3

Summary: 
      The purpose of this study is to determine if vitamin D as an adjuvant therapy can improve the
      outcome (i.e. fewer relapses) and the quality of life, including levels of physical activity,
      in children with newly diagnosed Crohn's disease (CD).
    

Detailed description: 
      Crohn's disease is a chronic inflammatory condition affecting all segments of the digestive
      tract from the mouth to the anus. This condition is associated with an increased risk of
      relapses throughout the course of the disease. Nearly 25% of patients with Crohn's disease
      are in the pediatric age range. Many epidemiological data are in favor of an increase
      incidence of pediatric Crohn's disease. Environmental factors could explain this increased
      incidence. Among them sunlight exposure and vitamin D deficiency have been suggested by many
      authors.

      Recent studies have described how varying doses of oral vitamin D supplementation can alter
      serum levels of 25 hydroxyvitamin D (25(OH)D), but no study has specifically addressed the
      question as to whether vitamin D supplementation can alter the rate of relapse/complications
      and/or quality of life in children diagnosed with CD.

      Current treatments of CD at diagnosis are effective around the time of diagnosis, but in the
      short and long term, some of these therapies are inefficient or lead to allergic or
      intolerance reactions. Altogether the rate of relapses in the year after diagnosis is
      significant. Thus, different therapeutic approaches must be investigated with the aim of
      lowering the burden of the disease.

      From November 2012 to July 2013, we conducted an open label pilot cohort study aiming to
      investigate the bioavailability and tolerance of high doses of vitamin D3 (3,000 IU or 4,000
      IU per day) administered orally as an adjunct therapy in 20 children with newly diagnosed
      pediatric CD (http://clinicaltrials.gov/ct2/show/NCT01692808). Data from laboratory studies,
      observational research and pilot trials taken together suggest that vitamin D can be of great
      importance in the genesis and progression of CD. Vitamin D deficiency could be a true risk
      factor for disease occurrence and/or relapses. The results of our pilot study demonstrate
      that in children with active CD at diagnosis, a daily dose of 4,000 IU of vitamin D is well
      tolerated and quickly increases the blood levels of 25OHD3 to 100 nmol/L or above in 100% of
      children with CD at diagnosis. Moreover a maintenance dosage of 2,000 IU a day is required
      (and sufficient) for maintaining this target over several months. Currently there is no
      adequately powered study in the pediatric CD population exploring the relationship between
      vitamin D therapy at diagnosis and CD outcomes.

      We propose a randomized controlled trial (RCT) to study the efficacy of high-dose oral
      vitamin D, as adjunct therapy, in children with newly diagnosed CD, to reduce the relapse
      rate and to improve patients' quality of life.

      Primary Efficacy End Point: The proportion of patient with at least one relapse 52 weeks
      after randomization.

      Secondary efficacy endpoint: Quality of life scores, Cumulative steroid dose, Time to first
      relapse, Duration of corticotherapy, Number of relapses, Number of hospitalizations Safety
      Endpoint : incidence of hypercalcemia (defined as a corrected serum calcium level >2.65
      mmol/L), incidence of hypercalciuria (defined as urinary calcium to creatinine molar ratio
      ≥1.50), incidence of supra-optimal levels of 25OHD3 as defined by a serum level ≥ 250 nmol/L,
      rate of study discontinuation due to hypercalcemia or hypercalciuria.

      Efficacy Variable: Occurrence of relapse, Time to relapse, Change in QoL score from baseline
      to 26 weeks, 52 weeks. Change in physical activity score from baseline to 26 weeks, 52 weeks.
    

Intervention name(s): Vitamin D3: 3000 or 4000 UI/day then 2,000 UI/day; Vitamin D3 800 UI/day then 800 UI/day
Intervention type(s): Drug; Drug
Intervention description(s): Weight at inclusion < 40 kg : 3 capsules of 1000 UI per day at induction and 2 capsules of 1000 UI per day at maintenance.
Weight at inclusion ≥ 40 kg : 4 capsules of 1000 UI per day at induction and 2 capsules of 1000 UI per day at maintenance.; Weight < 40 kg: 2 capsules of 400 UI per day and 1 capsules of placebo at induction and 2 capsules of 400 UI per day at maintenance
Weight ≥ 40 kg: 2 capsules of 400 UI per day and 2 capsules of placebo at induction and 2 capsules of 400 UI per day at maintenance
Other intervention name(s): Cholecalciferol; Cholecalciferol
Intervention MeSH terms: Vitamin D; Ergocalciferols; Cholecalciferol; Vitamins
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Treatment
Keywords: Crohn; vitamin D; remission; inflammation; tolerance