Ulcerative Colitis and Vitamin D Supplementation

Immunomodulating and Clinical Effects of Vitamin D on Remission Induction in Patients With Moderate and Severe Ulcerative Colitis, Undergoing Treatment With Infliximab.

Ulcerative colitis (UC) is an inflammatory disease involving the colonic mucosa, with bleedings and ulcerations. Consequences are destroyed mucosal barrier and increased permeability. Several cytokines are described to mediate the progressive course of ulcerative colitis and it is considered nowadays an immunologic disease. Patients with UC have often low levels of vitamin D and elevated prevalence of osteoporosis.

In vitro studies demonstrate that vitamin D has an immunomodulating effect, and may have a direct healing action on colonic mucosa has been described in animal studies. One can therefore rise a hypothesis that vitamin D supplementation could be crucial in patients with UC. To our knowledge, it has not been performed randomized clinical trials to study these possible effects of vitamin D and it has not been studied the effects of vitamin D on the relapse frequency and immunological composition of colic mucosa in patient with moderate to severe ulcerative colitis.

Objectives for our study are as follows: To examine if high-dose vitamin D supplementation in patients with moderate to severe ulcerative colitis:

• reduces relapse frequency and increase the duration of the Infliximab induced remission
• mediates and changes the cytokines composition in the colic mucosa
• decreases the excretion of calprotectin in feces and reduces the concentration of inflammation markers
• augments bone mass

Study Overview

• Status: Withdrawn
• Conditions: Ulcerative Colitis
• Intervention / Treatment: Drug: placebo; Drug: Vitamin D

• Study Type: Interventional
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Norway
  • Tromsø, Norway, 9014
    • University Hospital of North Norway

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Men and women older than18 years old, diagnosed with UC (either debut or relapsed chronic UC), moderate or severe, where it is an indication to treat with infliximab.

Exclusion Criteria:

• Primary hyperparathyroidism (PHPT)
• Sarcoidosis
• Renal failure (serum creatinine > 125 mumol/L in men or > 105 mumol/L in women)
• Those, who use solarium routinely are not included
• Pregnant or breastfeeding women, otherwise women of fertile age must be on approved birth control methods during the study
• Renal stones last 15 years
• Cancer of any origin, diagnosed during last 5 years
• Unstable angina pectoris

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Vitamin D; Decristol (cholecalciferol) 20000 IU per capsule 1 capsule per week	Drug: Vitamin D; compare how vitamin D influences the course of ulcerative colitis versus placebo; Other Names: Cholecalciferol
Placebo Comparator: Placebo; capsule with peanut oil	Drug: placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
number of patients with remission	Mandatory criterion of remission: clinical remission (defined as Mayo score <= 1, including endoscopic findings) and non-mandatory: laboratory (calprotectin < 100, WBC and SR within reference range). These criteria will be assessed at 12 month after the start of intervention	12 months after start of intervention

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
change in fecal calprotectin	change in fecal calprotectin compared to baseline value	12 months after start of intervention
change in bone mineral density (whole body)	change in bone mineral density in whole body, measured with DEXA (t-score and z-score)	12 months after the start of intervention
change in fecal calprotectin	change in fecal calprotectin	3 months
change in tnf-alpha levels in colonic mucosa	change in mucosal tnf-alpha levels. Biopsies will be taken with the forceps from the colonic mucosa (colon sigmoid) and stored in RNA later media for the further analysis for TNF alpha concentration with PCR method.	3 months
change in tnf-alpha (in colonic mucosa)	Biopsies and analysis will be carried out as described ata 3 months follow-up	12 months after baseline

Collaborators and Investigators

• Sponsor: University Hospital of North Norway
• Investigators: Principal Investigator: Elena Kamycheva, MD, PhD, Medical Clinic, University Hospital of North Norway

Study record dates

Study Major Dates

• Study Start: April 1, 2013
• Primary Completion (Actual): April 1, 2014
• Study Completion (Anticipated): December 1, 2016

Study Registration Dates

• First Submitted: April 30, 2013
• First Submitted That Met QC Criteria: May 2, 2013
• First Posted (Estimate): May 3, 2013

Study Record Updates

• Last Update Posted (Estimate): June 2, 2015
• Last Update Submitted That Met QC Criteria: June 1, 2015
• Last Verified: June 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Gastrointestinal Diseases; Gastroenteritis; Colonic Diseases; Intestinal Diseases; Inflammatory Bowel Diseases; Ulcer; Colitis; Colitis, Ulcerative; Physiological Effects of Drugs; Micronutrients; Vitamins; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Vitamin D; Cholecalciferol
• Other Study ID Numbers: 2009/1392-13 (REK); 2009-015649-21 (EudraCT Number)