Correction of Vitamin D Levels and Its Effect on Insulin Resistance and Weight Gain in Obese Youth
Condition: Obesity; Insulin Resistance; Vitamin D Deficiency
MeSH terms: Insulin Resistance; Vitamin D Deficiency
Study type: Interventional
Phase: Phase 2

Summary: 
      Vitamin D deficiency is extremely common in obese youth. In our obese population followed in
      the Endocrinology clinic at Children's Medical Center Dallas, vitamin D levels were inversely
      correlated with a measure of insulin resistance. We propose to show that correction of
      vitamin D levels in obese children and adolescents improves their insulin sensitivity. Obese
      youth presenting to the Center for Obesity and its Consequences on Health (COACH) clinic will
      be randomized to receive either the most recent Institute of Medicine (IOM) recommendations
      of minimum D3 dose of 600 IU/day (1), or receive higher doses of D3 such that the blood
      levels of vitamin D will be brought to a target level in either the low part or high part of
      the normal range. The goal is to determine if correction of vitamin D deficiency will improve
      insulin sensitivity in this group. Secondary goals include determining whether correction of
      vitamin D deficiency in obese adolescents and children results in less weight gain, and
      determining the amount of D3 required to correct vitamin D levels in this population.

      Our specific hypotheses are as follows:

      Hypothesis #1 Obese youth treated with Vitamin D3 who achieve low-normal 25-hydroxyvitamin D3
      (OHD) levels (30-50 ng/mL) or high-normal 25-OHD levels (60-80 ng/mL) will have improved
      insulin resistance, as measured by Homeostatic Model Assessment of Insulin Resistance
      (HOMA-IR), compared to those individuals with deficient 25-OHD levels (< 30 ng/mL).

      Hypothesis #2 Subjects with a higher BMI will have higher Vitamin D dose requirements than
      current IOM recommendations of 600 IU/day and will take a longer period of time to reach
      target 25-OHD levels.

      Hypothesis #3 Subjects with normal 25-OHD levels will demonstrate less weight gain compared
      to subjects on the control arm.
    

Detailed description: 
      Concise Summary of Project: The proposed study is a prospective, unblinded dose-ranging trial
      to examine in obese youth 1) the effect of correcting Vitamin D (Vit D) deficiency on insulin
      resistance, 2) the effect of correcting Vit D deficiency on weight gain, and 3) the amount of
      Vit D3 required to achieve Vit D sufficiency in obese adolescents. Subjects will be recruited
      from obese children and adolescents aged 6 to 17 years presenting to the COACH clinic, a
      referral clinic for obese children at Children's Medical Center of Dallas. Approximately 1300
      new patients are seen in the COACH clinic each year. Ethnicity will be self-assigned as
      African-American, Caucasian, Hispanic, or Other. The ethnic makeup of the COACH clinic over
      the last 20 months was as follows: African-American 25%, Caucasian 19.5%, Hispanic 52%, and
      Other 3.5%.

      As per standard practice in the COACH clinic, a height (cm), weight (kg), and blood pressure
      will be obtained, and body mass index (kg/m2) calculated for each patient. Fasting total
      cholesterol, LDL, HDL, triglyceride, 25-OHD, Hemoglobin A1c (A1c), and fasting insulin will
      be obtained, and an Oral Glucose Tolerance Test (OGTT) performed. The baseline estimate of
      insulin sensitivity is calculated from the fasting insulin and glucose values, and reported
      as the HOMA-IR. After Informed Consent has been obtained, participants will be randomized to
      either the Control group (5000 IU/wk), the Low-normal 25-OHD group (target 25-OHD 30-50
      ng/mL), or the High-normal 25-OHD group (target 25-OHD 60-80 ng/mL). A 25-OHD < 25 ng/mL will
      be confirmed. These groups will be matched for age (6-12 years versus 13-17 years) and
      ethnicity (Caucasian versus African-American verus Hispanic). Approximately 60 patients will
      be recruited for each group. Subject participation will continue until Vit D sufficiency has
      been documented for 4 consecutive months, at which point the fasting insulin and glucose
      values will be repeated for calculation of HOMA-IR and assessment of insulin sensitivity, and
      amount of weight gain will be measured.
    

Intervention name(s): Vitamin D3
Intervention type(s): Drug
Intervention description(s): Vitamin D3, liquid formulation, 5000 IU/mL.
Other intervention name(s): calcidiol
Intervention MeSH terms: Vitamin D; Cholecalciferol
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Obesity; Insulin Resistance; Vitamin D Deficiency; Children; Adolescents