The Effect of Vitamin D3 to Maintain Surgical Remission in Postoperative Crohn's Disease: a Placebo-controlled Randomized Trial
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 142
- 试验地点
- 1
- 主要终点
- Proportion of patients with clinically significant endoscopic recurrence at 6 months of vitamin D3 treatment postoperatively, defined as endoscopic Rutgeerts' score ≥i2.
研究概览
简要总结
The majority of patients with Crohn's disease (CD) need to undergo surgical bowel resection. Postoperative recurrence of the disease is virtually inevitable and continues to be one of the most challenging therapeutic problems in inflammatory bowel diseases. Medical treatments to prevent recurrence have had limited effect. Anti-tumor necrosis factor (TNF) agents appear promising but are hampered by immunogenicity, side effects and high cost.
Vitamin D has recently received a lot of scientific attention and was found to have strong anti-inflammatory and antifibrotic effects in gut and liver inflammation. Many CD patients appear to have deficiency in Vitamin D. A controlled trial to prevent relapse of CD in medical (not surgical) remission suggested a preventive effect for Vitamin D but marginally missed its endpoint because of lack of power.
The ultimate proof of the anti-inflammatory effect of Vitamin D in CD can best be studied in the prevention of postoperative recurrence.
详细描述
Our objective is to study the prophylactic effect of Vitamin D3 to prevent post-operative recurrence of Crohn's disease (CD), with an endoscopic endpoint 6 months after surgery as the primary outcome. Endoscopy has been an established surrogate marker for future clinical relapse. Secondary objectives include clinical recurrence rates at 6 months, the difference in recurrence rates among patients with and without low Vitamin D levels at baseline, the effects of Vitamin D3 on quality of life parameters, resource use and related costs.
ANTICIPATED OUTCOME This study will provide proof of the anti-inflammatory effect of vitamin D, which to our opinion can best be studied in a post-operative setting. Since post-operative recurrence is frequent, a safe and cost-effective therapy is highly needed for this indication. The hypothesis is that patients who receive vitamin D treatment will have less frequent and less severe endoscopic recurrence.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥ 18 years, either male or female
- •Established CD
- •First or second ileocolonic resection with ileocolonic anastomosis and removal of all tissue macroscopically affected by CD according to the surgeon
- •Able to give written informed consent
- •Normal levels of serum calcium at inclusion
- •Being able to resume oral intake within 2 weeks after surgery
排除标准
- •Patients in whom not all visible CD has been resected
- •Active fistulizing perianal disease (requiring anti TNF treatment)
- •Extensive small bowel resection
- •Third, fourth or later ileocolonic resection
- •Patients undergoing ileocoecal resection in the Lir!c Trial (NTR 1150, http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=1150)
- •A history of primary hyperparathyroidism
- •A history of osteoporosis for which calcium and Vitamin D treatment are mandatory
- •A history of another granulomatous diseases (sarcoidosis, tuberculosis)
- •Pregnant or breastfeeding (at index date) female patients
- •Patients undergoing other resections than ileocolonic resections
- •Patients who prefer to use open-label vitamin D preparations
- •Patients who will continue to use tanning beds
研究组 & 干预措施
Vitamin D
Weekly Vitamin D3 drops 25.000 IU for 6 months following ileocoecal resection
干预措施: Vitamin D (Drug)
Placebo
Weekly placebo drops for 6 months following ileocoecal resection
干预措施: Placebo (Drug)
结局指标
主要结局
Proportion of patients with clinically significant endoscopic recurrence at 6 months of vitamin D3 treatment postoperatively, defined as endoscopic Rutgeerts' score ≥i2.
时间窗: 0-6 months
次要结局
- 5. Any adverse events(0-6 months)
- 1. Clinical CD recurrence measured with CDAI among the 2 groups at week 26 (CDAI ≥220)(0-6 months)
- 2. NOD2 gene mutations: the difference in response to vitamin D treatment in patients NOD2+ versus patients NOD2-.(0-6 months)
- 4. Quality of life, measured by one validated questionnaire for IBD patients (IBD-Q) and two general questionnaires (SF-36 and EuroQol)(0-6 months)
- 3. Difference in significant recurrence among all patients with low vitamin D at baseline(0-6 months)
研究者
Geert D'Haens
MD, PhD
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)