The Effect of Vitamin D3 to Maintain Surgical Remission in Postoperative Crohn's Disease

Study Overview
=================
Brief Summary
-----------------
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.

Detailed Description
-----------------
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.

Official Title
-----------------
The Effect of Vitamin D3 to Maintain Surgical Remission in Postoperative Crohn's Disease: a Placebo-controlled Randomized Trial

Conditions
-----------------
Crohn's Disease

Intervention / Treatment
-----------------
* Drug: Vitamin D
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 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 Exclusion Criteria: 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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Vitamin D<br>Weekly Vitamin D3 drops 25.000 IU for 6 months following ileocoecal resection | Drug: Vitamin D<br>* 25.000 IU oral drops<br>|
| Placebo Comparator: Placebo<br>Weekly placebo drops for 6 months following ileocoecal resection | Drug: Placebo<br>* placebo oral drops<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients with clinically significant endoscopic recurrence at 6 months of vitamin D3 treatment postoperatively, defined as endoscopic Rutgeerts' score ≥i2. |  | 0-6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 3. Difference in significant recurrence among all patients with low vitamin D at baseline |  | 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 | 
| 5. Any adverse events |  | 0-6 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Crohn's disease, Vitamin D, Postoperative, Recurrence, Inflammatory bowel disease, Gastroenteritis, Gastrointestinal Diseases, Digestive System Diseases, Colonic Diseases, Intestinal Diseases, Pathologic Processes