Crohn's Disease, Inflammatory Bowel Disease, Ulcerative Colitis
Conditions
Keywords
IBD, Inflammatory Bowel Disease, Crohn's Disease, Ulcerative Colitis, Vitamin D
Brief summary
Research has shown that children with Inflammatory Bowel Disease may have lower levels of vitamin D than healthy children, especially in the winter. Vitamin D is important for growing and maintaining healthy bones throughout life, and this is particularly important, since children with IBD frequently have low bone density. It may also be helpful in the treatment of IBD itself, because it helps reduce inflammation. Vitamin D levels are measured by the amount of 25 OHD in the blood; however, measuring this level on a regular basis is not yet the standard for children with IBD. The purpose of this study is to find the best way to treat low vitamin D levels, and to maintain good vitamin D levels throughout the year. It will also test whether having higher vitamin D levels will improve the bone health of children with IBD, and whether it will help them have milder disease.
Detailed description
Vitamin D is essential for bone mineralization. The prevalence of vitamin D insufficiency \[serum 25-hydroxy-vitamin D concentration (25OHD) ≤ 20 ng/mL\] is high among adults with inflammatory bowel disease (IBD), and even higher in pediatric patients with IBD. Protein-losing enteropathy could represent both an etiologic factor for hypovitaminosis D, and an obstacle in treating it in IBD patients. There are currently no guidelines for the treatment of hypovitaminosis D in adults or children with IBD. Moreover we have obtained evidence that optimal vitamin D stores (25OHD ≥32 ng/mL) may not be maintained throughout the year in patients with IBD following current RDA recommendations. On the other hand, the prevalence of low bone mineral density is high among young patients with IBD, during a period in their lives when they should experience the most rapid acquisition of bone mass. Optimization of vitamin D status and its impact on the bone health of children with IBD has not been studied. In addition, vitamin D may play an important role in the regulation of the immune system as supported by animal models of colitis and in vitro human studies. Prospective studies of the effect of vitamin D supplementation on disease outcomes have not been undertaken in children with IBD to date. We aim to perform a) a randomized controlled trial to compare the efficacy of 3 regimens in treating vitamin D insufficiency in pediatric patients with IBD over a period of 6 weeks. We will also evaluate the effects of each regimen on markers of bone resorption, bone formation and parathyroid hormone levels, and the relationship between the magnitude of gastrointestinal protein loss, as reflected by clearance of fecal alpha -1-antitrypsin, and the efficacy of the treatment. b) We also aim to perform a randomized controlled trial to compare the efficacy of 2 regimens of different doses of oral vitamin D2 in maintaining optimal vitamin D stores in pediatric patients with IBD over a period of 2 years. We intend to study the effect of each regimen on a) bone mass acquisition (measured via DXA and pQCT) and bone strength (measured via pQCT), b) bone formation and resorption markers and parathyroid hormone, and c) disease outcomes and disease severity over the same period of time.
Interventions
DIETARY_SUPPLEMENTergocalciferol
8000 units/ml
DIETARY_SUPPLEMENTCholecalciferol
400 units per drop
Sponsors
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Crohn's and Colitis Foundation
NASPGHAN Foundation
Boston Children's Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
5 Years to 21 Years
Healthy volunteers
No
Inclusion criteria
* Clinical diagnosis of inflammatory bowel disease * serum 25OHD level ≤ 20 ng/mL (Treatment Trial) * serum 25OHD level \> 20 ng/mL (Maintenance Trial)
Exclusion criteria
* Patients unable to take medications by mouth, pregnant, with liver/kidney failure, receiving anticonvulsant medications (specifically, phenobarbital, carbamazepine and phenytoin, since they lead to increased vitamin D metabolism through hepatic induction of the cytochrome P450 (CYP450) hydroxylase enzymes), regularly attending a tanning salon (once weekly or more), currently being treated for hypovitaminosis D with therapeutic doses of vitamin D (\> 800 IU per day) and unwilling to discontinue this regimen. * patients on growth hormone, anabolic steroid hormones, calcitonin, bisphosphonates (Maintenance Trial only)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Treatment of Low 25 Hydroxy Vitamin D Levels in Pediatric Patients With Inflammatory Bowel Disease | 6 weeks | Change in serum 25OHD levels after treatment with vitamin D formulations for 6 weeks in pediatric patients with inflammatory bowel disease. 25OHD is the most abundant vitamin D metabolite, which is bound to vitamin D binding protein. The measurement of its concentration in serum, reflects vitamin D stores. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maintenance of 25 Hydroxy Vitamin D Levels in Pediatric Patients With Inflammatory Bowel Disease | 12 months | Percentage of pediatric patients with inflammatory bowel disease who maintained their serum 25OHD level at or above 32 ng/mL at all study visits over the duration of the maintenance study 25OHD is the most abundant vitamin D metabolite, which is bound to vitamin D binding protein. The measurement of its concentration in serum, reflects vitamin D stores. Concentration at or above 32 ng/mL has been identified as optimal vitamin D level for bone health by majority of experts. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Treatment A 2,000 IU/day of vitamin D2 orally for 6 weeks (control arm)
ergocalciferol: 8000 units/ml | 24 |
| Treatment B 2,000 IU/day of vitamin D3 orally for 6 weeks
Cholecalciferol: 400 units per drop | 24 |
| Treatment C 50,000 IU of vitamin D2 once a week orally for 6 weeks
ergocalciferol: 8000 units/ml | 23 |
| Maintenance A 400 IU/day of vitamin D2 orally over 2 years (control arm)
ergocalciferol: 8000 units/ml | 32 |
| Maintenance B 2,000 IU/day of vitamin D2 orally from November 1 to April 30, and 1,000 IU/day of vitamin D2 orally for the remainder of the year over 2 years
ergocalciferol: 8000 units/ml | 31 |
| Total | 134 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 | 1 | 0 | 0 |
| Overall Study | Lost to Follow-up | 4 | 0 | 2 | 4 | 7 |
| Overall Study | Physician Decision | 0 | 2 | 0 | 1 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 1 | 1 |
Baseline characteristics
| Characteristic | Total | Treatment A | Treatment B | Treatment C | Maintenance A | Maintenance B |
|---|---|---|---|---|---|---|
| Age, Continuous | 15.2 years STANDARD_DEVIATION 3.2 | 15.9 years STANDARD_DEVIATION 3 | 14.7 years STANDARD_DEVIATION 3.5 | 16.3 years STANDARD_DEVIATION 3.2 | 15.1 years STANDARD_DEVIATION 3.1 | 14.5 years STANDARD_DEVIATION 3.1 |
| Sex: Female, Male Female | 69 Participants | 10 Participants | 14 Participants | 9 Participants | 19 Participants | 17 Participants |
| Sex: Female, Male Male | 65 Participants | 14 Participants | 10 Participants | 14 Participants | 13 Participants | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 5 / 24 | 8 / 24 | 4 / 23 | 19 / 32 | 15 / 31 |
| serious Total, serious adverse events | 0 / 24 | 0 / 24 | 0 / 23 | 0 / 32 | 0 / 31 |
Outcome results
Primary
Treatment of Low 25 Hydroxy Vitamin D Levels in Pediatric Patients With Inflammatory Bowel Disease
Change in serum 25OHD levels after treatment with vitamin D formulations for 6 weeks in pediatric patients with inflammatory bowel disease. 25OHD is the most abundant vitamin D metabolite, which is bound to vitamin D binding protein. The measurement of its concentration in serum, reflects vitamin D stores.
Time frame: 6 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment A | Treatment of Low 25 Hydroxy Vitamin D Levels in Pediatric Patients With Inflammatory Bowel Disease | 9.3 ng/ml | Standard Deviation 1.8 |
| Treatment B | Treatment of Low 25 Hydroxy Vitamin D Levels in Pediatric Patients With Inflammatory Bowel Disease | 16.4 ng/ml | Standard Deviation 2 |
| Treatment C | Treatment of Low 25 Hydroxy Vitamin D Levels in Pediatric Patients With Inflammatory Bowel Disease | 25.4 ng/ml | Standard Deviation 2.5 |
Secondary
Maintenance of 25 Hydroxy Vitamin D Levels in Pediatric Patients With Inflammatory Bowel Disease
Percentage of pediatric patients with inflammatory bowel disease who maintained their serum 25OHD level at or above 32 ng/mL at all study visits over the duration of the maintenance study 25OHD is the most abundant vitamin D metabolite, which is bound to vitamin D binding protein. The measurement of its concentration in serum, reflects vitamin D stores. Concentration at or above 32 ng/mL has been identified as optimal vitamin D level for bone health by majority of experts.
Time frame: 12 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment A | Maintenance of 25 Hydroxy Vitamin D Levels in Pediatric Patients With Inflammatory Bowel Disease | 3 Participants |
| Treatment B | Maintenance of 25 Hydroxy Vitamin D Levels in Pediatric Patients With Inflammatory Bowel Disease | 3 Participants |