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

Study Overview
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Brief Summary
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The purpose of this study is to determine if high doses of vitamin D3 administered orally as adjunct therapy to children with Crohn's disease could improve the outcome of the disease.

Detailed Description
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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.

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

Conditions
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Crohn's Disease

Intervention / Treatment
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* Drug: Vitamin D3 3000 UI daily
* Drug: Vitamin D3 4000 UI daily


Participation Criteria
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Eligibility Criteria
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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 *

Ages Eligible for Study
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Minimum Age: 10 Years
Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Exclusive Enteral Nutrition<br>This group is one of the non interventional group. As enteral nutrition is one of the usual therapy of Crohn disease at diagnosis. | |
| Experimental: EEN + Vitamin D3 3000 UI daily<br>Exclusive Enteral Nutrition + Vitamin D3 3000 UI daily for one month This arm will be one of the two experimental arms. | Drug: Vitamin D3 3000 UI daily<br>* Vitamin D3 will be administered as an adjunct to corticosteroids or enteral nutrition at the doses of 3000 UI daily or 4000 UI daily<br>* Other names: Cholecalciferol;|
| No Intervention: Corticosteroïd<br>Corticosteroids (1mg/kg/day) associated with usual vitamin and calcium supplementation: vitamin D 800 IU of vitamin D3 + 1000 mg calcium per day) for one month | |
| Experimental: Corticosteroids + Vitamin D3 4000 UI<br>Corticosteroids (1mg/kg/day) associated with vitamin D3 4000 UI daily and calcium 1000 mg daily for one month | Drug: Vitamin D3 4000 UI daily<br>* This arm is intended for those at diagnosis treated with Corticosteroid or in Remission<br>* Other names: Cholecalciferol;|
| Experimental: Vitamin D3 4000 UI<br>Vitamin D3 4000 UI /day . This arm is intended for those children in remission with or without immunosuppressant. Vitamin D will be administered in adjunction to usual therapy. | Drug: Vitamin D3 4000 UI daily<br>* This arm is intended for those at diagnosis treated with Corticosteroid or in Remission<br>* Other names: Cholecalciferol;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with adverse events after one month | Tolerance will be assessed weekly by measuring clinical adverse events in relation with high blood level of 25 hydroxy vitamin D. Biological measures will also be performed including : Circulating level of Calcium, phosphorus, PTH. | up to 1 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Decrease of inflammatory parameters | Evaluate the change from baseline in effect in blood and fecal inflammatory parameters (erythrocyte sedimentation rate, C-reactive protein, faecal Calprotectin). | Baseline and 1 month | 
| Immunological changes | Evaluate the change from baseline in immunological parameters (lymphocytes CD3, CD4, CD8, Treg and iNKT, proliferation and activation of CD4 and CD8). | Baseline and 1 month | 
| Bioavailability | The bioavailability will be assessed by measuring the level of 25 hydroxy vitamin D at baseline then 24 hours after the first administration of vitamin D then weekly up to one month and compare this level to baseline. | Baseline, after 24 h and then weekly for one month | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Crohn, vitamin D, remission, inflammation, tolerance