Trial of High Dose Vitamin D in Patient's With Crohn's Disease

Study Overview
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Brief Summary
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Crohn's disease is more common in areas of the world with less sunlight exposure. Sunlight is a major source of vitamin D. There is some research to suggest that patient's with higher vitamin D levels are less likely to undergo surgeries and have better control of their disease. We intend to study the effects of high dose vitamin D supplementation in patients with vitamin D deficiency and Crohn's disease. We hypothesize that patients given high doses will have less hospitalizations, surgeries, steroid use.

Detailed Description
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Subjects are randomized to low or high dose vitamin D, and outcomes including steroid prescriptions, CD-related hospitalizations, CD-related surgeries, and the modified Harvey-Bradshaw Index are measured.

Official Title
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A Randomized Controlled Trial of High-Dose Vitamin D in Crohn's Disease

Conditions
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Crohn's Disease, Vitamin D Deficiency

Intervention / Treatment
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* Drug: Cholecalciferol 10,000 IU
* Drug: Cholecalciferol 400 IU


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of CD Age >= 18 and <75 Vitamin D deficiency or insufficiency (serum 25-hydroxyvitamin D < 30ng/ml) Exclusion Criteria: Corticosteroid use in the last 4 weeks CD-related surgery in the last 6 months CD-related hospitalization in the last 4 weeks Pregnancy, intended pregnancy during the study period or nursing Serum calcium >10.2 mg/dL History of primary sclerosing cholangitis History of undergoing an ileal pouch-anal anastomosis Current active perianal disease History of nephrolithiasis in the past 2 years Anticipated change in therapy in the next 30 days (steroids, biologic initiation) modified Harvey-Bradshaw Index of 10 or more History of decreased renal function (glomerular filtration rate <30ml/min based on MDRD) or polycystic kidney disease History of sarcoidosis History of hyperparathyroidism Any other chronic condition that may preclude high doses of Vitamin D such as lymphoma Concurrent use of hydrochlorothiazide, phenytoin, phenobarbital, carbamazepine or primidone Osteoporosis

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Single Group Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Low Dose Vitamin D<br>Patients will be given 400 IU cholecalciferol once daily for 30 days. <-THIS IS THE Active Comparator Intervention. To maintain the blind, a random few will be given another round at the 30 day mark. For patients who enroll in the summer, a random few will again receive 400 IU cholecalciferol in March. | Drug: Cholecalciferol 400 IU<br>* Cholecalciferol 400 IU po daily<br>* Other names: Low dose vitamin D;|
| Experimental: High Dose Vitamin D<br>Patients will be given cholecalciferol 10,000 IU daily for 30 days. <-THIS IS THE INTERVENTION. At that point, if their vitamin D levels remain below 50 ng/ml, the 30 day course will be repeated. For patients who enroll in the summer, levels will be rechecked in March and if <50 ng/ml, a 30 day course will be administered. | Drug: Cholecalciferol 10,000 IU<br>* Cholecalciferol 10,000 IU po daily<br>* Other names: High Dose Vitamin D;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Composite Endpoint: Number of Participants With (Any of) a CD-related Hospitalization, CD-related Surgery, CD-related ER Visits and Steroid Prescriptions | Composite endpoint of (any of) Crohn's disease(CD)-related hospitalizations, CD-related surgeries, CD-related ER visits, or steroid prescriptions. Originally planned to collect at Day 180 and Day 360. Only 1 subject remained in the study to Day 180 so that data is presented here. | Day 180 | 
| Hypercalcemia | Hypercalcemia is presented as number of participants with Calcium >10.8 mg/dl Originally planned to collect at Day 180 and Day 360. Only 1 subject remained in the study to Day 180 so that data is presented here. | Day 180 | 
| Incidence of Nephrolithiasis | Incidence of nephrolithiasis associated with hypercalcemia (>10.8mg/dl) documented by imaging Originally planned to collect at Day 180 and Day 360. Only 1 subject remained in the study to Day 180 so that data is presented here. | Day 180 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Crohn's Related Hospitalizations | Dichotomous (0/1) endpoint for each subject, depending on whether a CD-related hospitalization occurred. Relatedness to Crohn's disease as judged by the DSMB. Originally planned to collect at Day 180 and Day 360. Only 1 subject remained in the study to Day 180 so that data is presented here. | Day 180 | 
| Steroid Prescription Given (Dichotomous 0/1) | Originally planned to collect at Day 180 and Day 360. Only 1 subject remained in the study to Day 180 so that data is presented here. No steroid prescriptions occurred | Day 180 | 
| Crohn's Related Surgeries (Dichotomous 0/1 Per Subject) | Originally planned to collect at Day 180 and Day 360. Only 1 subject remained in the study to Day 180 so that data is presented here. No CD-related surgeries occurred in the 1 subject | Day 180 | 
| Change in Modified Harvey-Bradshaw Index (HBI Without Examination) | modified Harvey-Bradshaw is a disease assessment scale. 0 is the lowest score and would be considered remission. Scale ranges to over 16 (upper limit is defined by the number of bowel movements in the prior day) with numbers over 16 being severe disease. A positive change (such as that indicated below) therefore references slightly worsening disease while a negative change references improving disease. Originally planned to collect at Day 180 and Day 360. Only 1 subject remained in the study to Day 180 so that data is presented here. 1 subject had an increase of 1 unit on the modified HBI. | Day 180 | 
| Change in C-reactive Protein | Originally planned to collect at Day 180 and Day 360. Only 1 subject remained in the study to Day 180 so that data is presented here. The delta between first (baseline) and last CRP (Day 180) is reported here. | Day 180 | 
| Changes in Fecal Calprotectin | Originally planned to collect at Day 180 and Day 360. Results were not collected on any subjects, as the one participant did not provide a stool sample. | 1 year | 
| Percent With Escalation of Therapy | Patients who had to have a change in therapy Originally planned to collect at Day 180 and Day 360. Only 1 subject remained in the study to Day 180 so that data is presented here. | Day 180 | 
| Quality of Life Measure Changes | change in quality of life measures based on Inflammatory bowel disease questionnaire (IBD-Q). Scale from 0 to 224 with 0 being the poorest quality of life and 224 being the highest quality of life. A positive change indicates improvement while a negative change indicates worsening. Originally planned to collect at Day 180 and Day 360. Only 1 subject remained in the study to Day 180 so that data is presented here. | Day 180 | 
| Change in Fatigue Measurements | Change in FACIT-F scale over the year. Scale is 0-160 with 0 being no fatigue and 160 being extreme fatigue. A positive change indicates worsening in symptoms and a negative change indicates an improvement. Originally planned to collect at Day 180 and Day 360. Only 1 subject remained in the study to Day 180 so that data is presented here. | Day 180 | 
| Participants With at Least One Crohn's Related Emergency Department (ED) Visit | Originally planned to collect at Day 180 and Day 360. Only 1 subject remained in the study to Day 180 so that data is presented here. No CD-related ED visits occurred in the 1 subject | Day 180 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Crohn's disease, Vitamin D deficiency