Bioavailability of Vitamin D in Children and Adolescents With Crohn's Disease

Background : 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.

Vitamin D, in addition to its action on bone metabolism, exerts an anti-inflammatory effect by modulating the innate and acquired immune system. The biological effect of high doses of vitamin D administered orally have not been extensively studied in children with Crohn's disease. In these patients, the absorption and bioavailability of vitamin D may be altered in relation with mucosal lesions.

Objective :

Thus our aim is to investigate the effect of high doses of vitamin D3 administered orally as an adjunct therapy to children with newly diagnosed pediatric Crohn diseases or children in remission.

Methods : In this Prospective study 40 children will be enrolled and followed up for a duration of one month. The administration of vitamin D 3000 IU or 4000 IU per day will be considered as an adjunct to conventional therapy (steroids or enteral nutrition for patients at diagnosis or immunosuppressants for patients in remission).

Analysis:

• Tolerance will be assessed during weekly visits by a brief questionnaire and blood tests.
• Efficacy will be assessed by monitoring the change in fecal and blood inflammatory markers.
• Change in the immunological status will be assessed by measuring the following parameters :

• T lymphocyte count CD3, CD4, CD8, and invariant Natural Killer T cell, Treg.
• Proliferation and activation of CD4 and CD8 T lymphocytes induced by anti-CD3 antibody activator (OKT3). The activation will be evaluated by dosing CD25 and the proliferation by the study of cell cycle after 3 days of culture of total blood culture.
• The culture supernatants will be collected and frozen for subsequent analysis of cytokines Th1 and Th2 (IFN, IL2, IL4, IL13) with Affymetrix method that allows simultaneous determination of multiples cytokines.

Inclusion criteria

• Age between 10 and 18 years
• Crohn's disease diagnosed by usual clinical and endoscopic criteria
• Recent (less than one week) blood test with results of : Albumin, sedimentation rate, hematocrit

Exclusion criteria

• Known renal or cardiac malformation
• Disorders of phospho-calcic metabolism and vitamin D
• Intake of vitamin D supplementation in the last three months prior to enrollment
• Current intake of medications known to interfere with the metabolism of calcium, phosphate and vitamin D *