Pilot Pharmacokinetic Study of Daily Versus Monthly High-Dose Cholecalciferol Supplementation

Study Overview
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Brief Summary
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Research has shown that Vitamin D is important in preventing rickets in children, osteomalacia in adults, certain cancers, cardiovascular disease, Type 2 Diabetes, and metabolic syndrome. Data suggests that Vitamin D deficiency is common throughout the world. With increasing medical conditions being linked to Vitamin D deficiency, it is suggested that establishing early normal Vitamin D levels is important to long term health. There are low quantities of maternal Vitamin D that transfer from blood into breast milk. This places nursing infants at risk of developing low Vitamin D levels, and the American Academy of Pediatrics recommends they receive 400 international units (IU) of Vitamin D daily. If nursing mothers were supplemented with oral Vitamin D, this may produce adequate total Vitamin D in the breast milk for the growing infant to consume. By taking this potential therapeutic approach, this would prevent the burden of administering an oral Vitamin D liquid supplement to an infant. Recent laboratory technology now allows measurement of total Vitamin D (parent Vitamin D2 plus parent Vitamin D3). The main objective of this pilot study is to compare total Vitamin D levels resulting from daily Vitamin D supplementation of 5,000 international units of cholecalciferol (Vitamin D3) orally for 28 days vs. 150,000 international units of cholecalciferol orally once in healthy, non-pregnant, non-lactating female subjects aged 18 � 40. The research results will be used to help identify an optimal dosing regimen to administer to lactating mothers to hopefully deliver adequate total Vitamin D in nursing infants. This separate study will be conducted at a later date under a subsequent protocol. Previous research has demonstrated that Vitamin D3 levels become undetectable within 14 days after adult subjects received 100,000 international units of cholecalciferol. The investigators' central hypothesis is that daily dosing of 5,000 international units of cholecalciferol orally will maintain detectable total Vitamin D levels in serum after fourteen days, compared to high-dose 150,000 international units of oral cholecalciferol once. It is anticipated the aims of this pilot study will yield the following results. First, we, the investigators, hope to determine the resulting Vitamin D blood levels and calculate an appropriate dosing strategy for future research. Next we plan to measure the resulting 25,hydroxyvitamin D levels that correspond with these dosing regimens, since 25,hydroxyvitamin D is the major indicator of Vitamin D status in humans. Lastly, we will measure blood calcium and phosphorus levels to assure these doses of Vitamin D are tolerated by healthy female subjects.

Official Title
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Pilot Pharmacokinetic Study of Daily Versus Monthly High-Dose Cholecalciferol Supplementation

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Dietary Supplement: Single High Dose Cholecalciferol
* Dietary Supplement: Daily Dose Cholecalciferol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18 to 40 years non-pregnant non-lactating female willing to participate in study with adequate compliance and follow-up Exclusion Criteria: Any clinically significant underlying chronic disease states (i.e. diabetes, asthma, seizure disorders, hypo/hyperthyroidism, hypercalcemia, hypophosphatemia, other endocrine disorders, absorption disorders) allergy to study medication or its components significant travel south of the 35° North latitude in the 28-day study period chronic use of steroids, anti-convulsants, or barbiturates participation in indoor tanning practices during the 28-day study period

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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Female

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: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Single High Dose Supplementation<br>Age 18 to 40 years, non-pregnant, non-lactating, female subjects . | Dietary Supplement: Single High Dose Cholecalciferol<br>* Age 18 to 40 years, non-pregnant, non-lactating, female subjects will receive cholecalciferol 150,000 international units orally once (Bio-tech Pharmacal 50,000 IU capsule, Fayetteville, AR).<br>* Other names: Vitamin D3;|
| Active Comparator: Daily Dose Supplementation<br>Age 18 to 40 years, non-pregnant, non-lactating, female subjects. | Dietary Supplement: Daily Dose Cholecalciferol<br>* Age 18 to 40 years, non-pregnant, non-lactating, female subjects will receive cholecalciferol 5,000 IU capsule, Fayetteville, AR).<br>* Other names: Vitamin D3;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Vitamin D pharmacokinetics | Characterize the differences in pharmacokinetics of oral Vitamin D3 between two dosing regimens within women of child-bearing age by evaluating any changes in the number of days of detectable total serum Vitamin D and area under the curve (AUC) above baseline. | 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Vitamin D Supplementation Dosing Regimen | Determine a Vitamin D3 dosing regimen that produces more days of detectable total serum Vitamin D to be used in an additional study examining the quantity of maternal vitamin D that crosses into breast milk for feeding infants. | 28 days | 
| Vitamin D Supplementation Dosing Regimen Efficacy | Assess differences in change in baseline 25-OH-D between two dosing regimens. | 28 days | 
| Vitamin D Supplementation Safety | Monitor for any adverse effects of Vitamin D supplementation, specifically hypercalcemia and hypophosphatemia. | 28 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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healthy volunteers, healthy subjects, vitamin D, cholecalciferol, vitamin D3, total vitamin D