A Pragmatic Randomized Controlled Trial on High Dose Vitamin D to Prevent Relapses of Crohn's Disease in Children
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- 入组人数
- 316
- 试验地点
- 7
- 主要终点
- Relapse
研究概览
简要总结
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).
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
盲法说明
The vitamin D will be donated by a pharmaceutical company. It will be dispensed in anonymized bottles with the content similar in color and taste in order to keep patients unaware of their allocation. We will implement a number of study maneuvers aimed at minimizing measurement biases. These include: (1) masking of the data; (2) documenting the use of major co-interventions such as other multivitamin supplements.
入排标准
- 年龄范围
- 4 Years 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age at randomization between 4 and 17 years inclusively
- •Pediatric Crohn's Disease Activity Index (PCDAI) ≤ 10 with no clinical symptoms (abdominal pain or blood in the stool) at inclusion
- •Receiving a stable dose for at least 4 weeks of any of the following drugs: Thiopurines, Methotrexate, or TNF-α inhibitors (Infliximab/Adalimumab)
- •Dosage of fecal calprotectin lower than 250 µg/g stool at inclusion.
排除标准
- •History of surgery resulting in a permanent colostomy or ileostomy (because of the inability to calculate PCDAI at baseline)
- •Patients who have already been included in the pilots vitamin D trials
- •Patients actively enrolled in other CD drug trials.
研究组 & 干预措施
Experimental Arm:
Experimental: 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 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).
干预措施: vitamin D3 (Drug)
Control Arm:
Active Comparator: Vitamin D3 600 UI/day then 600 UI/day
600 UI/day as induction therapy for 4 weeks, then 600 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)).
干预措施: vitamin D3 (Drug)
结局指标
主要结局
Relapse
时间窗: Within 52 weeks after randomization in the study
A relapse is defined as the occurrence of clinical symptoms (\> 2 bowel movements per day, abdominal pain, fever, weight loss, perianal disease or extra-intestinal symptoms) and a pediatric Crohn's disease Activity Index (PCDAI) less than 10. The PCDAI is a validated and reproducible tool that was developed by consensus at a meeting of pediatric (Inflammatory bowel disease) IBD experts and subsequently validated in 12 North American institutions. It includes 11 domains, with clinical symptoms, physical examination, laboratory parameters, and growth. The PCDAI score can range from 0-100, with higher scores signifying more active disease. A score \< 10 is consistent with inactive disease; 11-30 indicates mild disease; \> 30 suggests moderate to severe disease. The PCDAI has been used in many pediatric trials.
次要结局
- Number of relapses per patient per year(Within 52 weeks after randomization in the study)
- Number of hospitalizations per year(Between randomization and Week 52)
- Lapse of time from randomization to first relapse(From date of randomization until the date of first relapse, assessed up to 52 weeks after randomization in the study)
- Improvement of the Quality of life(At week 26 and week 52)
研究者
Jantchou Prevost
Associate Professor of Pediatrics
St. Justine's Hospital