Clinical trial NCT02186275: The Vitamin D in Pediatric Crohn's Disease
Official title: Randomized Controlled Trial of High Dose Vitamin D in Children With Newly Diagnosed Crohn's Disease for the Prevention of Relapses
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Crohn's Disease
Keywords: Crohn
vitamin D
remission
inflammation
tolerance
Lead sponsor: St. Justine's Hospital
Sponsor class: OTHER
Collaborators: name: Canadian Institutes of Health Research (CIHR)
First posted: 2014-07-10
Enrollment: 25
Sex: ALL
Minimum age (years): 9
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Eligibility criteria: Eligibility Criteria:

- Diagnosis of CD by the usual clinical, endoscopic and histological criteria and classified according to the Paris classification

Inclusion Criteria:

* Age at randomization between 9 and 18 years inclusively
* Interval between diagnosis and randomization between 2 weeks and 6 months after the diagnosis
* Pediatric Crohn's Disease Activity Index (PCDAI) ≤ 30 at inclusion
* Concurrent treatment with corticosteroids and/or enteral nutrition and/or thiopurines (azathioprine, 6-mercaptopurine) and/or methotrexate and/or 5-aminosalicylic acid (5-ASA) and/or TNF-α inhibitors (Infliximab, Adalimumab).

Exclusion Criteria:

* Patient diagnosed with severe complex perianal fistulizing CD (defined as the presence at diagnosis of a high intersphincteric, transsphincteric, extrasphincteric, or suprasphincteric complex perianal fistula)
* Known chronic liver cholestasis (defined by an elevation of conjugated bilirubin and/or gamma glutamyl transferase \> 3 upper limit normal)
* Known renal dysfunction requiring chronic dialysis or creatinine ≥ 100 micromol/L.
* Known congenital bone disease
* Known cystic fibrosis or other exocrine pancreatic insufficiency.
* Currently treated with anticonvulsants metabolized through cytochrome P-450
* Unable to take oral capsule form.

Primary outcomes:
measure: Occurrence of at least one relapse within 52 weeks after randomization in the trial.
timeFrame: within 52 weeks after inclusion in the study
Secondary outcomes:
measure: the lapse of time from randomization to first relapse
timeFrame: from randomization to first relapse
measure: the number of relapses per patient per year
timeFrame: within 52 weeks after randomization in the trial
measure: the duration of corticotherapy
timeFrame: between randomization and 52 weeks later
measure: The number of CD related hospitalizations
timeFrame: between randomization and 52 weeks later
measure: The quality of life
timeFrame: at 26 weeks and 52 weeks
Other outcomes:
measure: Change in the level of physical activities
timeFrame: between randomization and 52 weeks later
measure: Changes in bone mineral density
timeFrame: between randomization and 52 weeks later
Locations:
city: Edmonton
country: Canada
facility: Edmonton Clinic Health Academy
state: Alberta
city: Vancouver
country: Canada
facility: University of British Columbia
state: British Columbia
city: Winnipeg
country: Canada
facility: Health Science Center Pediatric
state: Manitoba
city: St. John's
country: Canada
facility: Janeway Children's Health Centre
state: Newfoundland and Labrador
city: Halifax
country: Canada
facility: IWK Health Centre
state: Nova Scotia
city: Hamilton
country: Canada
facility: McMaster University
state: Ontario
city: Toronto
country: Canada
facility: Hospital for Sick Childrens
state: Ontario
city: Montreal
country: Canada
facility: Ste-Justine hospital
state: Quebec
city: Montréal
country: Canada
facility: Montreal Children's Hospital (Montreal).
state: Quebec
city: Québec
country: Canada
facility: Centre Hospitalier Universitaire Laval
Study officials:
affiliation: St. Justine's Hospital
name: Prevost Jantchou, MD
role: PRINCIPAL_INVESTIGATOR
References: