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

NCT ID: NCT02010762

Last Updated: 2017-12-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 142 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-02-28
• Study Completion Date: 2017-12-31

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.

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

Vitamin D

Weekly Vitamin D3 drops 25.000 IU for 6 months following ileocoecal resection

Group Type: ACTIVE_COMPARATOR

Vitamin D

Intervention Type: DRUG

25.000 IU oral drops

Placebo

Weekly placebo drops for 6 months following ileocoecal resection

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

placebo oral drops

Interventions

Vitamin D

25.000 IU oral drops

Intervention Type: DRUG

Placebo

placebo oral drops

Intervention Type: DRUG

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

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

Sponsors

Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

OTHER

Sponsor Role: lead

Responsible Party

Geert D'Haens

MD, PhD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Geert D'Haens, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Locations

Academic Medical Center

Amsterdam, , Netherlands

Countries

Netherlands

References

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.

Reference Type: DERIVED

PMID: 32461138 (View on PubMed)

Other Identifiers

NL.45391.018.13

Identifier Type: -

Identifier Source: org_study_id