Ulcerative Colitis and Vitamin D Supplementation

Study Overview
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Brief Summary
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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

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

Conditions
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Ulcerative Colitis

Intervention / Treatment
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* Drug: Vitamin D
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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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 |