Defining Vitamin D Insufficiency in School Age Children: A Randomized Placebo Controlled Trial of Vitamin D3

Study Overview
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Brief Summary
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The study objective is to characterize the threshold levels of serum 25-hydroxyvitamin D for the definition of vitamin D insufficiency in 8-14 year old African American and Caucasian children. We propose a 6 month randomized placebo controlled trial of vitamin D (vitamin D3 1000 IU/day vs. placebo) initiated during October through March (during fall and winter) in 8 to 14 year old African American and Caucasian children. The results of the trial will help establish the cutoff threshold value of serum 25(OH)D for defining vitamin D insufficiency in preadolescent and adolescent children. Safety of vitamin D supplementation will be assessed by measuring serum calcium at 0, 2 and 6 months and by monitoring for adverse events. Currently recommended adequate intake for vitamin D of 200 IU daily may not meet the body's daily needs for vitamin D. Therefore, it is likely that a higher level of daily vitamin D intake may be needed to meet the body's skeletal and non-skeletal demands for vitamin D. Determining the dietary required intake of vitamin D for the prevention of vitamin D insufficiency during childhood has immense public health potential for addressing health disparities and ensuring better bone health during adulthood. The primary outcome measure will be serum 25(OH)D and parathyroid hormone (PTH). The secondary outcome measures will include: markers of bone formation (serum P1NP) and bone resorption (serum CTX).We will also examine differences in serum 25(OH)D, PTH, and markers of bone turnover in African American vs. Caucasian children.

Detailed Description
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Epidemiologic and clinical data document a high prevalence of vitamin D insufficiency among adults and adolescents in the US. Vitamin D insufficiency during childhood has the potential to impact the acquisition of peak bone mass. Vitamin D insufficiency is also associated with several non-skeletal disorders including cancer (prostate, breast, and colon), diabetes mellitus (type 1 and type 2), and multiple sclerosis. In our pilot study nearly 50% of 6 to 10 year old African American children residing in Pittsburgh, Pennsylvania, were deemed vitamin D insufficient (serum 25-hydroxyvitamin D (25(OH)D): ≤ 20 ng/mL; Rajakumar K, et al. Clinical Pediatrics. 2005;44:683-692). To extend this field further, we are proposing a randomized placebo-controlled trial of vitamin D3 for establishing the serum 25-hydroxyvitamin D (25(OH)D) cutoff threshold levels for defining vitamin D insufficiency during childhood and to document the safety and efficacy of treatment on the vitamin D status of the study cohort. A total of 168 (African American: 84, Caucasian: 84) 8 to 14 year old preadolescent and adolescent children will undergo a randomized-placebo controlled trial (RCT) of vitamin D3 1000 IU daily vs. placebo for 6 months initiated during fall and winter (October through March). Safety of vitamin D supplementation will be assessed by measuring serum calcium at 0, 2 and 6 months and by monitoring for adverse events. We will also examine the differences in serum 25(OH)D, PTH, and markers of bone turnover in African American vs. Caucasian children. The primary outcome measure will be serum 25(OH)D and PTH. The secondary outcome measures will include: markers of bone formation: serum osteocalcin (OC) and bone resorption: serum C-terminal cross-linking telopeptide of type 1 collagen (serum CTX). Additional outcomes will include: dietary intake of vitamin D and calcium, skin color (Fitzpatrick Sunreactive Skin Type and Melanin Index), sun exposure, and body mass index. Vitamin D deficiency will be defined as serum 25-hydroxyvitamin D concentrations <20 ng/mL. Public health importance of childhood vitamin D insufficiency is linked to the impact of vitamin D status on the acquisition of peak bone mass. Reduced peak bone mass can predispose to premature onset of osteoporosis and increase the risk for osteoporosis related fragility fractures. Achieving and maintaining vitamin D sufficiency during childhood can positively impact the skeletal health of children and reduce their osteoporosis burden during adulthood, and modify their risk for the non-skeletal disorders associated with chronic vitamin D insufficiency. Paucity of data regarding threshold levels of serum 25(OH)D associated with vitamin D insufficiency status among school age children and the likelihood that the serum 25(OH)D threshold levels for vitamin D sufficiency could be different among African American and Caucasian children makes it compelling for this issue to be explored. Based on expert opinion and supportive data in the medical literature, we feel that the currently recommended adequate intake for vitamin D for pre- and adolescent children (200 IU daily) is woefully inadequate to meet the daily needs for vitamin D. Therefore, it is likely that a higher level of daily vitamin D intake may be needed to meet the body's skeletal and non-skeletal demands for vitamin D. This study will determine the serum 25(OH)D cutoff for the definition of vitamin D insufficiency and document the safety and efficacy of treatment on vitamin D status.

Official Title
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Defining Vitamin D Insufficiency in School Age Children: A Randomized Placebo Controlled Trial of Vitamin D3

Conditions
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Healthy

Intervention / Treatment
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* Dietary Supplement: Vitamin D3 1000 IU
* Dietary Supplement: Placebo Tablet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age: 8-14 years Race: African American or Caucasian Children not taking multivitamins for at least 1 month before enrollment and agree not to start any multivitamin supplements during the 6-month trial period. Children who are on multivitamins can be considered for enrollment only if they are able to and agree to stop their multivitamin tablet for a 1 month washout period prior to enrollment. Absence of chronic diseases that could affect growth or calcium or vitamin D metabolism Exclusion Criteria: Hepatic or renal disease Metabolic rickets Malabsorptive disorders (Crohn's disease, cystic fibrosis and celiac disease) or cancer Treatment with anticonvulsants or systemic glucocorticoids

Ages Eligible for Study
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Minimum Age: 8 Years
Maximum Age: 14 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vitamin D3<br>Vitamin D3 1000 IU Tablet | Dietary Supplement: Vitamin D3 1000 IU<br>* Vitamin D3 1000 IU Tablet once daily for 6 months<br>|
| Placebo Comparator: Placebo<br>Placebo Tablet | Dietary Supplement: Placebo Tablet<br>* Placebo Tablet once daily for 6 months<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum 25-hydroxyvitamin D | Circulating concentration of 25 hydroxyvitamin D is a biomarker of vitamin D status. Vitamin D deficiency was defined as serum 25-hydroxyvitamin D concentrations <20 ng/mL. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Parathyroid Hormone (PTH) Dietary Data |  | 6 months | 
| Osteocalcin (OC) | Marker of bone formation | 6 months | 
| Collagen Type 1 Cross-linked C-telopeptide (CTx) | Collagen type 1 cross-linked C-telopeptide (CTx) is a marker of bone resorption. | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Vitamin D Deficiency, Vitamin D Insufficiency, Child, Adolescent, African American, Caucasian, Definition, Preadolescent