Crohn's Disease, Vitamin D Deficiency
Conditions
Keywords
Crohn's disease, Vitamin D deficiency
Brief summary
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
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.
Interventions
DRUGCholecalciferol 10,000 IU
Cholecalciferol 10,000 IU po daily
DRUGCholecalciferol 400 IU
Cholecalciferol 400 IU po daily
Sponsors
Crohn's and Colitis Foundation
University of Michigan
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Composite Endpoint: Number of Participants With (Any of) a CD-related Hospitalization, CD-related Surgery, CD-related ER Visits and Steroid Prescriptions | Day 180 | 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. |
| Hypercalcemia | Day 180 | 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. |
| Incidence of Nephrolithiasis | Day 180 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Modified Harvey-Bradshaw Index (HBI Without Examination) | Day 180 | 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. |
| Change in C-reactive Protein | Day 180 | 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. |
| Changes in Fecal Calprotectin | 1 year | 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. |
| Crohn's Related Hospitalizations | Day 180 | 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. |
| Quality of Life Measure Changes | Day 180 | 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. |
| Change in Fatigue Measurements | Day 180 | 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. |
| Participants With at Least One Crohn's Related Emergency Department (ED) Visit | Day 180 | 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 |
| Percent With Escalation of Therapy | Day 180 | 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. |
| Steroid Prescription Given (Dichotomous 0/1) | Day 180 | 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 |
| Crohn's Related Surgeries (Dichotomous 0/1 Per Subject) | Day 180 | 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 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Low Dose Vitamin D Patients will be given 400 IU cholecalciferol once daily for 30 days. 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.
Cholecalciferol 400 IU | 6 |
| High Dose Vitamin D Patients will be given cholecalciferol 10,000 IU daily for 30 days. 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.
Cholecalciferol 10,000 IU | 5 |
| Total | 11 |
Baseline characteristics
| Characteristic | Low Dose Vitamin D | High Dose Vitamin D | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 1 Participants | 0 Participants | 1 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 5 Participants | 5 Participants | 10 Participants |
| Age, Continuous | 34.2 years STANDARD_DEVIATION 14.2 | 35.2 years STANDARD_DEVIATION 9 | 34.6 years STANDARD_DEVIATION 11.5 |
| Region of Enrollment United States | 6 participants | 5 participants | 11 participants |
| Sex: Female, Male Female | 4 Participants | 3 Participants | 7 Participants |
| Sex: Female, Male Male | 2 Participants | 2 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 5 |
| other Total, other adverse events | 0 / 6 | 1 / 5 |
| serious Total, serious adverse events | 0 / 6 | 0 / 5 |
Outcome results
Primary
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.
Time frame: Day 180
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| High Dose Vitamin D | Composite Endpoint: Number of Participants With (Any of) a CD-related Hospitalization, CD-related Surgery, CD-related ER Visits and Steroid Prescriptions | 0 participants |
Primary
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.
Time frame: Day 180
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| High Dose Vitamin D | Hypercalcemia | 0 Participants |
Primary
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.
Time frame: Day 180
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| High Dose Vitamin D | Incidence of Nephrolithiasis | 0 Participants |
Secondary
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.
Time frame: Day 180
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| High Dose Vitamin D | Change in C-reactive Protein | 0 mg/dL |
Secondary
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.
Time frame: Day 180
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| High Dose Vitamin D | Change in Fatigue Measurements | -3 units on a scale |
Secondary
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.
Time frame: Day 180
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| High Dose Vitamin D | Change in Modified Harvey-Bradshaw Index (HBI Without Examination) | 1 units on a scale (0-16) |
Secondary
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.
Time frame: 1 year
Population: Results were not collected on any subjects
Secondary
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.
Time frame: Day 180
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| High Dose Vitamin D | Crohn's Related Hospitalizations | 0 CD-related hospitalization occurred |
Secondary
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
Time frame: Day 180
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| High Dose Vitamin D | Crohn's Related Surgeries (Dichotomous 0/1 Per Subject) | 0 CD-related surgery occurred |
Secondary
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
Time frame: Day 180
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| High Dose Vitamin D | Participants With at Least One Crohn's Related Emergency Department (ED) Visit | 0 participants |
Secondary
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.
Time frame: Day 180
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| High Dose Vitamin D | Percent With Escalation of Therapy | 0 Participants |
Secondary
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.
Time frame: Day 180
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| High Dose Vitamin D | Quality of Life Measure Changes | -7 units on a scale |
Secondary
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
Time frame: Day 180
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| High Dose Vitamin D | Steroid Prescription Given (Dichotomous 0/1) | 0 Steroid prescription occurred |