Trial of High Dose Vitamin D in Patient's With Crohn's Disease (RODIN-CD)

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

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.

Study Overview

• Status: Terminated
• Conditions: Vitamin D Deficiency; Crohn's Disease
• Intervention / Treatment: Drug: Cholecalciferol 400 IU; Drug: Cholecalciferol 10,000 IU

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 11
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Indiana
    • Indianapolis, Indiana, United States, 46001
      • Indiana University
  • Iowa
    • Iowa City, Iowa, United States, 55240
      • University of Iowa
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • University of North Carolina

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Low Dose Vitamin D; 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; Cholecalciferol 400 IU po daily; Other Names: Low dose vitamin D
Experimental: High Dose Vitamin D; 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; Cholecalciferol 10,000 IU po daily; Other Names: High Dose Vitamin D

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Michigan
• Collaborators: Crohn's and Colitis Foundation
• Investigators: Principal Investigator: Peter D. Higgins, MD, PhD, MSc, University of Michigan; Study Director: Shail M Govani, M.D., M.Sc., University of Michigan; Study Director: Hans Herfarth, MD, PhD, University of North Carolina

Publications and helpful links

General Publications

• Jorgensen SP, Agnholt J, Glerup H, Lyhne S, Villadsen GE, Hvas CL, Bartels LE, Kelsen J, Christensen LA, Dahlerup JF. Clinical trial: vitamin D3 treatment in Crohn's disease - a randomized double-blind placebo-controlled study. Aliment Pharmacol Ther. 2010 Aug;32(3):377-83. doi: 10.1111/j.1365-2036.2010.04355.x. Epub 2010 May 11.
• Khalili H, Huang ES, Ananthakrishnan AN, Higuchi L, Richter JM, Fuchs CS, Chan AT. Geographical variation and incidence of inflammatory bowel disease among US women. Gut. 2012 Dec;61(12):1686-92. doi: 10.1136/gutjnl-2011-301574. Epub 2012 Jan 11.
• Cantorna MT, Munsick C, Bemiss C, Mahon BD. 1,25-Dihydroxycholecalciferol prevents and ameliorates symptoms of experimental murine inflammatory bowel disease. J Nutr. 2000 Nov;130(11):2648-52. doi: 10.1093/jn/130.11.2648.
• Ananthakrishnan AN, Khalili H, Higuchi LM, Bao Y, Korzenik JR, Giovannucci EL, Richter JM, Fuchs CS, Chan AT. Higher predicted vitamin D status is associated with reduced risk of Crohn's disease. Gastroenterology. 2012 Mar;142(3):482-9. doi: 10.1053/j.gastro.2011.11.040. Epub 2011 Dec 9.

Study record dates

Study Major Dates

• Study Start: April 1, 2015
• Primary Completion (Actual): April 1, 2016
• Study Completion (Actual): April 1, 2016

Study Registration Dates

• First Submitted: August 1, 2014
• First Submitted That Met QC Criteria: August 1, 2014
• First Posted (Estimate): August 5, 2014

Study Record Updates

• Last Update Posted (Actual): October 6, 2017
• Last Update Submitted That Met QC Criteria: August 31, 2017
• Last Verified: August 1, 2017

More Information

Terms related to this study

• Keywords: Crohn's disease; Vitamin D deficiency
• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Nutrition Disorders; Gastroenteritis; Intestinal Diseases; Avitaminosis; Deficiency Diseases; Malnutrition; Inflammatory Bowel Diseases; Vitamin D Deficiency; Crohn Disease; Physiological Effects of Drugs; Micronutrients; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Vitamin D; Cholecalciferol; Vitamins; Ergocalciferols
• Other Study ID Numbers: CCFA-329225