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

NCT ID: NCT01692808

Last Updated: 2015-11-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-10-31
• Study Completion Date: 2014-11-30

Brief Summary

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

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:

1. Tolerance will be assessed during weekly visits by a brief questionnaire and blood tests.

2. Efficacy will be assessed by monitoring the change in fecal and blood inflammatory markers.

3. 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.

Conditions

Crohn's Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Exclusive Enteral Nutrition

This group is one of the non interventional group. As enteral nutrition is one of the usual therapy of Crohn disease at diagnosis.

Group Type: NO_INTERVENTION

No interventions assigned to this group

EEN + Vitamin D3 3000 UI daily

Exclusive Enteral Nutrition + Vitamin D3 3000 UI daily for one month This arm will be one of the two experimental arms.

Group Type: EXPERIMENTAL

Vitamin D3 3000 UI daily

Intervention Type: DRUG

Vitamin D3 will be administered as an adjunct to corticosteroids or enteral nutrition at the doses of 3000 UI daily or 4000 UI daily

Corticosteroïd

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

Group Type: NO_INTERVENTION

No interventions assigned to this group

Corticosteroids + Vitamin D3 4000 UI

Corticosteroids (1mg/kg/day) associated with vitamin D3 4000 UI daily and calcium 1000 mg daily for one month

Group Type: EXPERIMENTAL

Vitamin D3 4000 UI daily

Intervention Type: DRUG

This arm is intended for those at diagnosis treated with Corticosteroid or in Remission

Vitamin D3 4000 UI

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.

Group Type: EXPERIMENTAL

Vitamin D3 4000 UI daily

Intervention Type: DRUG

This arm is intended for those at diagnosis treated with Corticosteroid or in Remission

Interventions

Vitamin D3 3000 UI daily

Vitamin D3 will be administered as an adjunct to corticosteroids or enteral nutrition at the doses of 3000 UI daily or 4000 UI daily

Intervention Type: DRUG

Vitamin D3 4000 UI daily

This arm is intended for those at diagnosis treated with Corticosteroid or in Remission

Intervention Type: DRUG

Other Intervention Names

Cholecalciferol; Cholecalciferol

Eligibility Criteria

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 *

• Minimum Eligible Age: 10 Years
• Maximum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

St. Justine's Hospital

OTHER

Sponsor Role: lead

Responsible Party

Jantchou Prevost

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Prevost Jantchou, MD, PHD

Role: PRINCIPAL_INVESTIGATOR

mother-child university hospital Ste. Justine Montreal-Canada

Locations

Mother-child university hospital

Montreal, Quebec, Canada

Countries

Canada

References

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.

Reference Type: BACKGROUND

PMID: 24247650 (View on PubMed)

Nerich V, Jantchou P, Boutron-Ruault MC, Monnet E, Weill A, Vanbockstael V, Auleley GR, Balaire C, Dubost P, Rican S, Allemand H, Carbonnel F. Low exposure to sunlight is a risk factor for Crohn's disease. Aliment Pharmacol Ther. 2011 Apr;33(8):940-5. doi: 10.1111/j.1365-2036.2011.04601.x. Epub 2011 Feb 20.

Reference Type: RESULT

PMID: 21332762 (View on PubMed)

Other Identifiers

JP2012042

Identifier Type: -

Identifier Source: org_study_id