Clinical trial NCT03999580: The Vitamin D in Pediatric Crohn's Disease ( ViDiPeC-2 )
Official title: A Pragmatic Randomized Controlled Trial on High Dose Vitamin D to Prevent Relapses of Crohn's Disease in Children
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Crohn Disease
Keywords: Crohn
vitamin D
remission
inflammation
tolerance
Lead sponsor: St. Justine's Hospital
Sponsor class: OTHER
First posted: 2019-06-26
Enrollment: 316
Sex: ALL
Minimum age (years): 4
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Time zero for each patient will be the day of randomization. Patients will be randomly assigned (1:1 ratio) in one of two study arms:

3,000 or 4,000 IU/day, according to the patient body weight, as induction for 4 weeks then 2,000 IU/day as maintenance for 48 weeks. Control: 600 IU/day of Vitamin D as induction (4 weeks) and maintenance (48 weeks).
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 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 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: Inclusion Criteria:

1. Age at randomization between 4 and 17 years inclusively
2. Pediatric Crohn's Disease Activity Index (PCDAI) ≤ 10 with no clinical symptoms (abdominal pain or blood in the stool) at inclusion
3. Receiving a stable dose for at least 4 weeks of any of the following drugs: Thiopurines, Methotrexate, or TNF-α inhibitors (Infliximab/Adalimumab)
4. Dosage of fecal calprotectin lower than 250 µg/g stool at inclusion.

Exclusion Criteria:

1. History of surgery resulting in a permanent colostomy or ileostomy (because of the inability to calculate PCDAI at baseline)
2. Patients who have already been included in the pilots vitamin D trials
3. Patients actively enrolled in other CD drug trials.

Primary outcomes:
measure: Relapse
timeFrame: Within 52 weeks after randomization in the study
Secondary outcomes:
measure: Lapse of time from randomization to first relapse
timeFrame: From date of randomization until the date of first relapse, assessed up to 52 weeks after randomization in the study
measure: Number of relapses per patient per year
timeFrame: Within 52 weeks after randomization in the study
measure: Number of hospitalizations per year
timeFrame: Between randomization and Week 52
measure: Improvement of the Quality of life
timeFrame: At week 26 and week 52
Other outcomes:
measure: Change in the level of physical activities
timeFrame: Between randomization and 52 weeks
Locations:
city: Edmonton
country: Canada
facility: Stollery Children's Hospital
state: Alberta
city: Vancouver
country: Canada
facility: BC Children's Hospital
state: British Columbia
city: Winnipeg
country: Canada
facility: Children's Hospital
state: Manitoba
city: Hamilton
country: Canada
facility: McMaster University
state: Ontario
city: London
country: Canada
facility: London Health Sciences Centre
state: Ontario
city: Montréal
country: Canada
facility: Montreal Children's Hospital
state: Quebec
city: Montréal
country: Canada
facility: CHU Sainte-Justine
state: Quebec
Study officials:
affiliation: St. Justine's Hospital
name: Prevost Jantchou, MD,PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Jantchou, P., Mailhot, G., Ezri, J., Le Deist, F., Deslandres, C., & Delvin, E. (2014). P-102: Bioavailability and tolerance of high doses vitamin D in children with newly diagnosed Crohn's disease. Journal of Crohn's and Colitis, 8, S432. doi:10.1016/s1873-9946(14)50130-4
citation: Jantchou P, Clavel-Chapelon F, Racine A, Kvaskoff M, Carbonnel F, Boutron-Ruault MC. High residential sun exposure is associated with a low risk of incident Crohn's disease in the prospective E3N cohort. Inflamm Bowel Dis. 2014 Jan;20(1):75-81. doi: 10.1097/01.MIB.0000436275.12131.4f.