- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01532349
Vitamin D as a Modifier of Serum Hepcidin in Children With Chronic Kidney Disease (D-fense)
Cholecalciferol as a Modifier of Serum Hepcidin in Children With Chronic Kidney Disease
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Vitamin D Supplementation is a practical and inexpensive intervention which is safe, readily available and clinically indicated. Substantial recent evidence suggests vitamin D may modify inflammatory pathways in CKD. There is a high probability of benefit and a low probability of harm for this easily modifiable factor. 25D levels can be effectively modified through oral supplementation with cholecalciferol. To the best of our knowledge, no studies examining the effects of oral cholecalciferol supplementation on hepcidin levels have been conducted in children with either CKD or other diseases.
We will conduct a randomized open-label controlled trial of oral cholecalciferol supplementation in children aged 1-21 years with stage 2-5 (pre-dialysis) CKD receiving regular nephrology follow-up at a tertiary-care children's hospital (Johns Hopkins Children's Center). The intervention model will be parallel assignment. Children will be randomly allocated to receive either cholecalciferol supplementation 4000 IU per day (28,000 IU weekly) according to the KDOQI recommended supplementation for children with mild 25D deficiency, or will be treated with 400 IU/day (2,800 IU/weekly), which is the recommended dietary allowance.(1) Allocation will be double-blinded to prevent knowledge of allocation status affecting interpretation of results. Study participants will be prescribed any clinically indicated additional cholecalciferol supplementation once the 3-month laboratory measures have been obtained, based on serum 25D levels at the end of the study period.(1) We are proposing a supplementation dose of 4000 IU/day in children with CKD, which is considered a safe dose by KDOQI standards; vitamin D2 doses as high as 10,000 IU/day have been given to French patients with CKD for > 1 year with no evidence of vitamin D toxicity.(2) 25D levels between 40 and 80 are indicative of "sufficiency", and a safe upper limit of intake, in which the risk of hypercalcemia is negligible, has been defined as 10,000 IU/day.(3, 4) Cholecalciferol will be provided in both tablet (vitamin D 2000 IU tablets and 400 IU tablets, National Vitamin Company, Casa Grande, AZ) and liquid (Enfamil® D-Vi-Sol™ Drops, 400 IU per mL) form, based on the ability to tolerate and preference of the subject.
Participants will be monitored for signs of 25D toxicity (hypercalcemia, hyperphosphatemia, hypercalciuria) during the follow up period of 1 month and 3 months from baseline.
Data Safety Monitoring Board will review serum calcium, phosphorus, and urine calcium:creatinine ratio values at the one month visit; if subjects show evidence of hypercalcemia or hyperphosphatemia (serum values > upper limit of normal, age-specific values, see Table 3 below), study drug will be discontinued.(3) If subjects demonstrate evidence of hypercalciuria (urine calcium:cr ratio > 0.6 in 1-2 year olds or > 0.2 in > 2 year olds) study drug will be discontinued.(5) In addition, if 25-hydroxy vitamin D levels > 80 ng/mL are reached, the study drug will be discontinued. In any subject in whom study drug is discontinued, the 3-month laboratory data will still be collected.
In the case of hypoalbuminemia (serum albumin < 3.5 g/dL) corrected total serum calcium will be calculated using the formula: Corrected calcium (mg/dL) = serum calcium (mg/dL) + 0.8 (4 - serum albumin [g/dL])(2) Standardized blood pressure measurement will include three manual BP measurements conducted after five minutes of rest with an aneroid sphygmomanometer, at least 30 seconds apart.
- KDOQI Work Group. KDOQI clinical practice guideline for nutrition in children with CKD: 2008 update. executive summary. Am J Kidney Dis. 2009 Mar;53(3 Suppl 2):S11-104.
- KDOQI clinical practice guidelines for bone metabolism and disease in children with chronic kidney disease. Am J Kidney Dis. 2005;46(Supplement 1):S1-S122.
- Querfeld U, Mak RH. Vitamin D deficiency and toxicity in chronic kidney disease: In search of the therapeutic window. Pediatr Nephrol. 2010 Jun 22.
- Shroff R, Knott C, Rees L. The virtues of vitamin D--but how much is too much? Pediatr Nephrol. 2010 Sep;25(9):1607-20.
- Kruse K, Kracht U, Kruse U. Reference values for urinary calcium excretion and screening for hypercalciuria in children and adolescents. Eur J Pediatr. 1984 Nov;143(1):25-31.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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Maryland
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Baltimore, Maryland, United States, 21287
- Johns Hopkins University
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Clinical diagnosis of stage 2-5 Chronic Kidney Disease (estimated glomerular filtration rate [GFR] between 15 and < 90 ml/min/1.73m2) based on the new bedside Schwartz formula estimation using serum creatinine and height [height in cm x 0.413/serum creatinine]
- 1-21 years of age
- Willingness and ability to provide informed consent and assent
Exclusion Criteria:
- Children less than 1 year of age (in whom risk of vitamin D toxicity may be increased) or greater than 21 years at time of study screening
- Children with a documented history of hypercalcemia or nephrolithiasis
- Children with GI tract discontinuity (ostomy)
- Current pregnancy or pregnancy within the last 12 months
- Children with known anemia-related disorders including sickle cell anemia, thalassemia
- Children with severe 25D deficiency (< 5 ng/mL) likely to be associated with severe morbidity and requiring prompt high dose vitamin D supplementation, or with 25D levels > 60 ng/mL which could be associated with increased risk of vitamin D toxicity
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: 400 IU vitamin D
Children will be randomly allocated to receive cholecalciferol supplementation 400 IU/day (2,800 IU/weekly), which is the recommended dietary allowance.
Study participants will be prescribed any clinically indicated additional cholecalciferol supplementation once the 3-month laboratory measures have been obtained, based on serum 25D levels at the end of the study period.
|
Children will be randomly allocated to receive either cholecalciferol supplementation 4000 IU per day 400 IU/day.
We are proposing a supplementation dose of 4000 IU/day in children with CKD, which is considered a safe dose by KDOQI standards; vitamin D2 doses as high as 10,000 IU/day have been given to French patients with CKD for > 1 year with no evidence of vitamin D toxicity.
Cholecalciferol will be provided in both tablet and liquid form, based on the ability to tolerate and preference of the subject.
Participants will be monitored for signs of 25D toxicity (hypercalcemia, hyperphosphatemia, hypercalciuria) during the follow up period of 1 month and 3 months from baseline.
Other Names:
|
Active Comparator: 4000 IU vitamin D
Children will be randomly allocated to receive cholecalciferol supplementation 4000 IU/day (28,000 IU weekly) according to the KDOQI recommended supplementation for children with mild 25D deficiency.
Study participants will be prescribed any clinically indicated additional cholecalciferol supplementation once the 3-month laboratory measures have been obtained, based on serum 25D levels at the end of the study period.
|
Children will be randomly allocated to receive either cholecalciferol supplementation 4000 IU per day 400 IU/day.
We are proposing a supplementation dose of 4000 IU/day in children with CKD, which is considered a safe dose by KDOQI standards; vitamin D2 doses as high as 10,000 IU/day have been given to French patients with CKD for > 1 year with no evidence of vitamin D toxicity.
Cholecalciferol will be provided in both tablet and liquid form, based on the ability to tolerate and preference of the subject.
Participants will be monitored for signs of 25D toxicity (hypercalcemia, hyperphosphatemia, hypercalciuria) during the follow up period of 1 month and 3 months from baseline.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in Serum Hepcidin With Vitamin D Intervention for Children With Chronic Kidney Disease
Time Frame: change from baseline to up to three months
|
The null hypothesis to be tested is that Vitamin D supplementation will not be associated with a decrease in serum hepcidin over the study period.
Statistical analysis will be performed as intention-to-treat.
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change from baseline to up to three months
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Meredith Atkinson, MD, MHS, Johns Hopkins University
Publications and helpful links
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- NA_00066175
- 1K23DK084116-01A2 (U.S. NIH Grant/Contract)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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