The Vitamin D in Pediatric Crohn's Disease

NCT ID: NCT02186275

Last Updated: 2020-09-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 25 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-02-29
• Study Completion Date: 2019-12-20

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.

Conditions

Crohn's Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Vitamin D3 3000 or 4000 UI/day then 2,000 UI/day

3000 UI or 4,000 UI/day as induction therapy (according to weight) for 4 weeks then 2,000 UIday as maintenance therapy for 48 weeks.

The administration of vitamin D will be considered as an adjunct to conventional therapy (corticosteroids, exclusive enteral nutrition or immunosuppressive agents (ISA)).

Group Type: EXPERIMENTAL

Vitamin D3: 3000 or 4000 UI/day then 2,000 UI/day

Intervention Type: DRUG

• Weight at inclusion < 40 kg : 3 capsules of 1000 UI per day at induction and 2 capsules of 1000 UI per day at maintenance.
• Weight at inclusion ≥ 40 kg : 4 capsules of 1000 UI per day at induction and 2 capsules of 1000 UI per day at maintenance.

Vitamin D3 800 UI/day then 800 UI/day

800 UI/day as induction therapy for 4 weeks, then 800 UI/day as maintenance therapy for 48 weeks. The administration of vitamin D will be considered as an adjunct to conventional therapy (corticosteroids, exclusive enteral nutrition or immunosuppressive agents (ISA)).

Group Type: ACTIVE_COMPARATOR

Vitamin D3 800 UI/day then 800 UI/day

Intervention Type: DRUG

• Weight < 40 kg: 2 capsules of 400 UI per day and 1 capsules of placebo at induction and 2 capsules of 400 UI per day at maintenance
• Weight ≥ 40 kg: 2 capsules of 400 UI per day and 2 capsules of placebo at induction and 2 capsules of 400 UI per day at maintenance

Interventions

Vitamin D3: 3000 or 4000 UI/day then 2,000 UI/day

• Weight at inclusion < 40 kg : 3 capsules of 1000 UI per day at induction and 2 capsules of 1000 UI per day at maintenance.
• Weight at inclusion ≥ 40 kg : 4 capsules of 1000 UI per day at induction and 2 capsules of 1000 UI per day at maintenance.

Intervention Type: DRUG

Vitamin D3 800 UI/day then 800 UI/day

• Weight < 40 kg: 2 capsules of 400 UI per day and 1 capsules of placebo at induction and 2 capsules of 400 UI per day at maintenance
• Weight ≥ 40 kg: 2 capsules of 400 UI per day and 2 capsules of placebo at induction and 2 capsules of 400 UI per day at maintenance

Intervention Type: DRUG

Other Intervention Names

Cholecalciferol; Cholecalciferol

Eligibility Criteria

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.

• Minimum Eligible Age: 9 Years
• Maximum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Canadian Institutes of Health Research (CIHR)

OTHER_GOV

Sponsor Role: collaborator

St. Justine's Hospital

OTHER

Sponsor Role: lead

Responsible Party

Jantchou Prevost

MD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Prevost Jantchou, MD

Role: PRINCIPAL_INVESTIGATOR

St. Justine's Hospital

Locations

Edmonton Clinic Health Academy

Edmonton, Alberta, Canada

University of British Columbia

Vancouver, British Columbia, Canada

Health Science Center Pediatric

Winnipeg, Manitoba, Canada

Janeway Children's Health Centre

St. John's, Newfoundland and Labrador, Canada

IWK Health Centre

Halifax, Nova Scotia, Canada

McMaster University

Hamilton, Ontario, Canada

Hospital for Sick Childrens

Toronto, Ontario, Canada

Montreal Children's Hospital (Montreal).

Montreal, Quebec, Canada

Ste-Justine hospital

Montreal, Quebec, Canada

Centre Hospitalier Universitaire Laval

Québec, , Canada

Countries

Canada

Other Identifiers

JP2014

Identifier Type: -

Identifier Source: org_study_id