Vitamin D Levels in Children With IBD

• Sponsor: Boston Children's Hospital (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00621257
• Collaborator: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (NIH), Crohn's and Colitis Foundation (Other), NASPGHAN Foundation (Other)
• Enrollment: 134
• Location: 1
• Arms: 5
• Duration (Months): 37.9
• Patients Per Site Per Month: 3.5

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Inflammatory Bowel Disease; Crohn's Disease; Ulcerative Colitis	Dietary Supplement: ergocalciferol; Dietary Supplement: Cholecalciferol	N/A

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 134 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Optimization of Vitamin D Stores and Its Impact on the Bone Health and Disease Outcomes of Children and Adolescents With IBD.
• Study Start Date: Jan 1, 2008
• Actual Primary Completion Date: Mar 1, 2011
• Actual Study Completion Date: Mar 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Treatment A 2,000 IU/day of ergocalciferol orally for 6 weeks (control arm)	Dietary Supplement: ergocalciferol; 8000 units/ml; Other Names: Vitamin D2
Experimental: Treatment B 2,000 IU/day of cholecalciferol orally for 6 weeks	Dietary Supplement: Cholecalciferol; 400 units per drop; Other Names: Vitamin D3
Experimental: Treatment C 50,000 IU of ergocalciferol once a week orally for 6 weeks	Dietary Supplement: ergocalciferol; 8000 units/ml; Other Names: Vitamin D2
Active Comparator: Maintenance A 400 IU/day of ergocalciferol orally over 2 years (control arm)	Dietary Supplement: ergocalciferol; 8000 units/ml; Other Names: Vitamin D2
Experimental: Maintenance B 2,000 IU/day of ergocalciferol orally from November 1 to April 30, and 1,000 IU/day of ergocalciferol orally for the remainder of the year over 2 years	Dietary Supplement: ergocalciferol; 8000 units/ml; Other Names: Vitamin D2

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 5 Years to 21 Years
• Sexes Eligible for Study: All
• Accepts 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)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Children's Hospital, Boston	Boston	Massachusetts	United States	02115

Sponsors and Collaborators

• Boston Children's Hospital
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Crohn's and Colitis Foundation
• NASPGHAN Foundation

Investigators

• Principal Investigator: Helen Pappa, MD, MPH, Boston Children's Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Helen Pappa, Assistant Professor, Boston Children's Hospital
• ClinicalTrials.gov Identifier: NCT00621257
• Other Study ID Numbers: 1K23DK076979-01A1; 1K23DK076979-01A1
• First Posted: Feb 22, 2008
• Last Update Posted: Mar 22, 2017
• Last Verified: Feb 1, 2017

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Helen Pappa, Assistant Professor, Boston Children's Hospital: IBD; Inflammatory Bowel Disease; Crohn's Disease; Ulcerative Colitis; Vitamin D
• Additional relevant MeSH terms: Crohn Disease; Colitis; Colitis, Ulcerative; Intestinal Diseases; Inflammatory Bowel Diseases; Ulcer; Vitamin D; Ergocalciferols; Cholecalciferol; Vitamins

Study Results

Participant Flow

Arm/Group Title	Treatment A	Treatment B	Treatment C	Maintenance A	Maintenance B
Arm/Group Description	2,000 IU/day of vitamin D2 orally for 6 weeks (control arm) ergocalciferol: 8000 units/ml	2,000 IU/day of vitamin D3 orally for 6 weeks Cholecalciferol: 400 units per drop	50,000 IU of vitamin D2 once a week orally for 6 weeks ergocalciferol: 8000 units/ml	400 IU/day of vitamin D2 orally over 2 years (control arm) ergocalciferol: 8000 units/ml	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
Period Title: Overall Study
STARTED	24	24	23	32	31
COMPLETED	20	21	20	26	22
NOT COMPLETED	4	3	3	6	9

Baseline Characteristics

Arm/Group Title	Treatment A	Treatment B	Treatment C	Maintenance A	Maintenance B	Total
Arm/Group Description	2,000 IU/day of vitamin D2 orally for 6 weeks (control arm) ergocalciferol: 8000 units/ml	2,000 IU/day of vitamin D3 orally for 6 weeks Cholecalciferol: 400 units per drop	50,000 IU of vitamin D2 once a week orally for 6 weeks ergocalciferol: 8000 units/ml	400 IU/day of vitamin D2 orally over 2 years (control arm) ergocalciferol: 8000 units/ml	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	Total of all reporting groups
Overall Participants	24	24	23	32	31	134
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	15.9 (3)	14.7 (3.5)	16.3 (3.2)	15.1 (3.1)	14.5 (3.1)	15.2 (3.2)
Sex: Female, Male (Count of Participants)
Female	10 41.7%	14 58.3%	9 39.1%	19 59.4%	17 54.8%	69 51.5%
Male	14 58.3%	10 41.7%	14 60.9%	13 40.6%	14 45.2%	65 48.5%

Outcome Measures

1. Primary Outcome

Title	Treatment of Low 25 Hydroxy Vitamin D Levels in Pediatric Patients With Inflammatory Bowel Disease
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment A	Treatment B	Treatment C
Arm/Group Description	2,000 IU/day of vitamin D2 orally for 6 weeks (control arm) ergocalciferol: 8000 units/ml	2,000 IU/day of vitamin D3 orally for 6 weeks Cholecalciferol: 400 units per drop	50,000 IU of vitamin D2 once a week orally for 6 weeks ergocalciferol: 8000 units/ml
Measure Participants	24	24	23
Mean (Standard Deviation) [ng/ml]	9.3 (1.8)	16.4 (2.0)	25.4 (2.5)

2. Secondary Outcome

Title	Maintenance of 25 Hydroxy Vitamin D Levels in Pediatric Patients With Inflammatory Bowel Disease
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Maintenance A	Maintenance B
Arm/Group Description	400 IU/day of vitamin D2 orally over 2 years (control arm) ergocalciferol: 8000 units/ml	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
Measure Participants	32	31
Count of Participants [Participants]	3 12.5%	3 12.5%

Adverse Events

Time Frame	6 weeks while participant was on study medication for treatment trial
Adverse Event Reporting Description	For 1 year, while participant was on study medication for the maintenance trial.
Arm/Group Title	Treatment A		Treatment B		Treatment C		Maintenance A		Maintenance B
Arm/Group Description	2,000 IU/day of vitamin D2 orally for 6 weeks (control arm) ergocalciferol: 8000 units/ml		2,000 IU/day of vitamin D3 orally for 6 weeks Cholecalciferol: 400 units per drop		50,000 IU of vitamin D2 once a week orally for 6 weeks ergocalciferol: 8000 units/ml		400 IU per day of oral vitamin D2 ergocalciferol 8000 IU/ml		1,000 IU of oral vitamin D2 per day from May to October and 2,000 IU of oral vitamin D2 per day of oral vitamin D2 per day from November to April ergocalciferol 8000 IU/ml
All Cause Mortality
	Treatment A		Treatment B		Treatment C		Maintenance A		Maintenance B
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Treatment A		Treatment B		Treatment C		Maintenance A		Maintenance B
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/24 (0%)		0/24 (0%)		0/23 (0%)		0/32 (0%)		0/31 (0%)
Other (Not Including Serious) Adverse Events
	Treatment A		Treatment B		Treatment C		Maintenance A		Maintenance B
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/24 (20.8%)		8/24 (33.3%)		4/23 (17.4%)		19/32 (59.4%)		15/31 (48.4%)
Cardiac disorders
irregular heart beat	0/24 (0%)	0	0/24 (0%)	0	1/23 (4.3%)	1	0/32 (0%)	0	0/31 (0%)	0
Eye disorders
sensitive eyes	0/24 (0%)	0	0/24 (0%)	0	1/23 (4.3%)	1	1/32 (3.1%)	1	1/31 (3.2%)	1
Gastrointestinal disorders
Constipation	0/24 (0%)	0	1/24 (4.2%)	1	1/23 (4.3%)	1	2/32 (6.3%)	2	4/31 (12.9%)	4
Dry mouth	0/24 (0%)	0	1/24 (4.2%)	1	0/23 (0%)	0	5/32 (15.6%)	5	3/31 (9.7%)	3
Loss of appetite	1/24 (4.2%)	1	2/24 (8.3%)	2	0/23 (0%)	0	4/32 (12.5%)	4	2/31 (6.5%)	2
Nausea	3/24 (12.5%)	3	1/24 (4.2%)	1	2/23 (8.7%)	2	5/32 (15.6%)	5	4/31 (12.9%)	4
Vomiting	0/24 (0%)	0	0/24 (0%)	0	1/23 (4.3%)	1	3/32 (9.4%)	3	1/31 (3.2%)	1
abdominal pain	0/24 (0%)	0	1/24 (4.2%)	1	1/23 (4.3%)	1	0/32 (0%)	0	0/31 (0%)	0
Metallic taste	0/24 (0%)	0	0/24 (0%)	0	0/23 (0%)	0	2/32 (6.3%)	2	1/31 (3.2%)	1
General disorders
Unusual tiredness, or weakness	0/24 (0%)	0	0/24 (0%)	0	0/23 (0%)	0	4/32 (12.5%)	4	3/31 (9.7%)	3
Musculoskeletal and connective tissue disorders
Bone pain	1/24 (4.2%)	1	0/24 (0%)	0	1/23 (4.3%)	1	3/32 (9.4%)	3	2/31 (6.5%)	2
Muscle pain	0/24 (0%)	0	0/24 (0%)	0	1/23 (4.3%)	1	3/32 (9.4%)	3	0/31 (0%)	0
Nervous system disorders
Drowsiness	0/24 (0%)	0	0/24 (0%)	0	1/23 (4.3%)	1	4/32 (12.5%)	4	5/31 (16.1%)	5
headache	0/24 (0%)	0	1/24 (4.2%)	1	0/23 (0%)	0	5/32 (15.6%)	5	2/31 (6.5%)	2
Increased thirst	1/24 (4.2%)	1	2/24 (8.3%)	2	1/23 (4.3%)	1	4/32 (12.5%)	4	5/31 (16.1%)	5
Renal and urinary disorders
Increased urination	0/24 (0%)	0	1/24 (4.2%)	1	1/23 (4.3%)	1	2/32 (6.3%)	2	1/31 (3.2%)	1
Skin and subcutaneous tissue disorders
itching skin	0/24 (0%)	0	2/24 (8.3%)	2	1/23 (4.3%)	1	2/32 (6.3%)	2	1/31 (3.2%)	1
Rash on face and body	0/24 (0%)	0	1/24 (4.2%)	1	0/23 (0%)	0	0/32 (0%)	0	0/31 (0%)	0
Calcium deposit in tissues outside of bones	0/24 (0%)	0	0/24 (0%)	0	0/23 (0%)	0	0/32 (0%)	0	1/31 (3.2%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.