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

NCT02010762 | Completed Phase 4 DMC

• 1 other identifier: NL.45391.018.13
• Study Type: interventional
• Target: 142
• Locations: 1 country
• Sites: 1

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.

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• 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

Study Arms (2)

Vitamin D

ACTIVE COMPARATOR

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

Drug: Vitamin D

Placebo

PLACEBO COMPARATOR

Weekly placebo drops for 6 months following ileocoecal resection

Drug: Placebo

Interventions

Vitamin D DRUG

25.000 IU oral drops

Vitamin D

Placebo DRUG

placebo oral drops

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• Being able to resume oral intake within 2 weeks after surgery

You may not qualify if:

• 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

Sponsors & Collaborators

• Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA): lead

Study Sites (1)

Academic Medical Center

Amsterdam, 1105 BK, Netherlands

Location

Related Publications (1)

• 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.

  PMID: 32461138 DERIVED

MeSH Terms

Conditions

Crohn Disease; Recurrence; Inflammatory Bowel Diseases; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Colonic Diseases; Intestinal Diseases; Pathologic Processes

Interventions

Vitamin D

Condition Hierarchy (Ancestors)

Disease Attributes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Secosteroids; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Geert D'Haens, MD, PhD

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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, PhD

Study Record Dates

• First Submitted: December 10, 2013
• First Posted: December 13, 2013
• Study Start: February 1, 2013
• Primary Completion: December 1, 2017
• Study Completion: December 1, 2017
• Last Updated: December 7, 2017

Record last verified: 2017-12

Locations

NL (1)