Clinical trial NCT02010762: The Effect of Vitamin D3 to Maintain Surgical Remission in Postoperative Crohn's Disease
Official title: The Effect of Vitamin D3 to Maintain Surgical Remission in Postoperative Crohn's Disease: a Placebo-controlled Randomized Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Crohn's Disease
Keywords: Crohn's disease
Vitamin D
Postoperative
Recurrence
Inflammatory bowel disease
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Colonic Diseases
Intestinal Diseases
Pathologic Processes
Lead sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Sponsor class: OTHER
First posted: 2013-12-13
Enrollment: 142
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

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

Primary outcomes:
measure: Proportion of patients with clinically significant endoscopic recurrence at 6 months of vitamin D3 treatment postoperatively, defined as endoscopic Rutgeerts' score ≥i2.
timeFrame: 0-6 months
Secondary outcomes:
measure: 1. Clinical CD recurrence measured with CDAI among the 2 groups at week 26 (CDAI ≥220)
timeFrame: 0-6 months
measure: 2. NOD2 gene mutations: the difference in response to vitamin D treatment in patients NOD2+ versus patients NOD2-.
timeFrame: 0-6 months
measure: 3. Difference in significant recurrence among all patients with low vitamin D at baseline
timeFrame: 0-6 months
measure: 4. Quality of life, measured by one validated questionnaire for IBD patients (IBD-Q) and two general questionnaires (SF-36 and EuroQol)
timeFrame: 0-6 months
measure: 5. Any adverse events
timeFrame: 0-6 months
Other outcomes:
Locations:
city: Amsterdam
country: Netherlands
facility: Academic Medical Center
Study officials:
affiliation: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
name: Geert D'Haens, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: de Bruyn JR, Bossuyt P, Ferrante M, West RL, Dijkstra G, Witteman BJ, Wildenberg M, Hoentjen F, Franchimont D, Clasquin E, van der Bilt JD, Tollens T, Bemelman WA, D'Hoore A, Duijvestein M, D'Haens GR; Dutch-Belgian The Effect of Vitamin D3 to Prevent Postoperative Relapse of Crohn's Disease: A Placebo-controlled Randomized Trial Study Group. High-Dose Vitamin D Does Not Prevent Postoperative Recurrence of Crohn's Disease in a Randomized Placebo-Controlled Trial. Clin Gastroenterol Hepatol. 2021 Aug;19(8):1573-1582.e5. doi: 10.1016/j.cgh.2020.05.037. Epub 2020 May 24.