Vitamin D3 Supplementation Pilot Study

Study Overview
=================
Brief Summary
-----------------
The purpose of this research study is to determine whether taking vitamin D, every day, over a 12 week period will improve the vitamin D status, risks for poor heart health, risks for developing type 2 diabetes, and/or muscle strength in overweight, African American teenagers with low vitamin D levels.

Detailed Description
-----------------
Vitamin D deficiency/insufficiency is common throughout the lifespan, and across all race and ethnic groups. The American Academy of Pediatrics (AAP) recently recommended supplementation dose to 400 international units (IU) daily in all children. These recommendations target rickets prevention, but address neither the vitamin D supplementation necessary to optimize bone health nor the nontraditional vitamin D roles in immune disease, insulin resistance, muscle function, and cardiovascular disease (CVD). Moreover, the AAP recommendation noted that it had little pediatric data upon which to base guidelines. The Institute of Medicine also recently published Dietary Reference Intakes for Calcium and Vitamin D: the estimated average requirement in children and adults was set at 400(IU) daily and the recommend dietary allowance was set at 600 IU daily. Data on outcomes and supplementation levels in African Americans (a population at particular risk for vitamin D deficiency) and across pediatric age ranges and body habitus types, are lacking. The Vitamin D supplementation requirement in obese, African American adolescents is particularly problematic since obesity is associated with 1) lower circulating vitamin D levels (25OHD) and 2) insulin resistance. This pilot study will examine the effect of vitamin D supplementation upon 25OHD, the serum marker of vitamin D status, in obese, African American adolescents with vitamin D deficiency. Subjects will be randomized to receive cholecalciferol 1000 IU or 5000 IU daily for 3 months. Serum 25OHD, parathyroid hormone, glucose, insulin, CVD risk markers, and measures of muscle function and pain will be obtained at baseline and post-treatment. This pilot study will provide data on serum 25OHD responses to vitamin D at doses more likely to meaningfully impact 25OHD than the current American Academy of Pediatrics (AAP) supplementation guideline. Responses to supplementation can then inform future clinical trials aimed at addressing outcomes of vitamin D replacement on insulin sensitivity and CVD risk in obese adolescents.

Official Title
-----------------
Pilot Study of Vitamin D3 Supplementation and Outcomes in Vitamin D Deficient Obese, African American Adolescents

Conditions
-----------------
Vitamin D Deficiency

Intervention / Treatment
-----------------
* Dietary Supplement: Cholecalciferol
* Dietary Supplement: Cholecalciferol


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: African American Obese [body mass index (BMI) greater than or equal to 95th percentile for age and sex] Pubertal (Tanner Stage greater than 1) 25OHD less than 20 ng/mL (for treatment phase); if 25OHD is greater than or equal to 20 ng/mL, only baseline data will be obtained. Committed to adherence to supplementation and study completion Exclusion Criteria: Pregnancy Chronic medical conditions or medications use that can affect growth, nutrition, bone health, vitamin D metabolism, glucose, or insulin sensitivity Known history of hypercalcemia or hypercalciuria Non-English speaking, as assessments are available only in English

Ages Eligible for Study
-----------------
Minimum Age: 12 Years
Maximum Age: 17 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Vitamin D3 supplementation of 1000 IU<br> | Dietary Supplement: Cholecalciferol<br>* 1000 IU by mouth, once daily for 3 months.<br>* Other names: Vitamin D;|
| Active Comparator: Vitamin D3 supplementation of 5000 IU<br> | Dietary Supplement: Cholecalciferol<br>* 5000 IU by mouth, once daily for 3 months.<br>* Other names: Vitamin D;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum 25OHD before and after treatment | The analysis will be an intention-to-treat method in which subjects are assumed to obtain all vitamin D supplements from the study and from no other sources, and all subjects are assumed to comply with their assigned dose and daily use. For the main contrasts of interest (5000 IU vs 1000 IU doses as well as serum 25OHD concentrations), we propose a longitudinal mixed effects model with time measurements at 0 and 12 weeks. | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adiponectin level comparison | Adiponectin level comparison before and at post-treatment | 12 weeks | 
| Lipid panel comparison | Lipid panel comparison before and at post-treatment | 12 weeks | 
| Lipoprotein subclass particles comparison | Lipoprotein subclass particles comparison before and at post-treatment | 12 weeks | 
| High-sensitivity C-Reactive Protein (hsCRP) comparison | High-sensitivity C-Reactive Protein (hsCRP) comparison before and at post-treatment | 12 weeks | 
| Insulin level comparison | Insulin level comparison before and at post-treatment | 12 weeks | 
| Total and undercarboxylated osteocalcin level comparison | Total and undercarboxylated osteocalcin level comparison before and at post-treatment | 12 weeks | 
| Muscle strength comparison | Muscle strength comparison before and at post-treatment | 12 weeks | 
| Musculoskeletal pain comparison | Musculoskeletal pain comparison before and at post-treatment | 12 weeks | 
| Blood pressure comparison | Blood pressure comparison before and at post-treatment | 12 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Vitamin D deficiency