Importance of Dosing Regimen for the Effect of Vitamin D Supplementation

Study Overview
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Brief Summary
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Vitamin D is a hormone with effects not only on the skeleton, but on most tissues in the body. Lack of vitamin D is associated with cardio-vascular disease (CVD), type 2 diabetes, cancer, infectious and immunological diseases, as well as risk factors for these diseases. However, intervention studies with vitamin D have been inconclusive regarding diseases and risk factors. This could be due to inclusion of subjects already vitamin D sufficient, and short and underpowered studies. In addition, there are indications that the dosing regimens may be important, so that daily doses with vitamin D are more efficient than intermittent doses, which so far have been generally used. This could be related to the concentration of circulating and thereby intracellular vitamin D concentrations, which probably is dependent on daily vitamin D doses. This will be tested in the present study where 60 subjects will be randomized to vitamin D 160 000 once, vitamin D 4000 IU/day, or placebo for four weeks. The primary endpoints will be effects on serum hepcidin and plasma cathelicidin after 4 weeks, with effects on serum PTH, RNA expression and microRNA in peripheral blood, telomerase activity in peripheral blood mononuclear cells and the ration between serum 1,25(OH)2D and 24,25(OH)2D as secondary endpoints.

Official Title
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Importance of Dosing Regimen for the Effect of Vitamin D Supplementation

Conditions
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Hypovitaminosis D

Intervention / Treatment
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* Drug: Vitamin D
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria:- Males and females 20 - 70 years 20 kg/m2 > BMI < 35 kg/m2 systolic BP < 175 mmHg, diastolic BP < 105 mmHg Serum 25(OH)D level < 50 nmol/L. Serum 25(OH)D < 50 nmol/L is considered as vitamin D deficiency, and accordingly, effects of vitamin D supplementation will be easier to detect than if the included subjects were vitamin D sufficient. Hgb, SR, CRP, creatinine < 130 umol/L in males, < 120 umol/L in females, calcium, FT4 and TSH within the normal reference range; ASAT < 90 mU/L ALAT < 140 U/L, HbA1c < 6.6 % The subjects must agree not to take any vitamin D supplementation, including cod liver oil or mølje, use solarium or go on sunny vacation during the intervention period. Exclusion Criteria: subjects allergic to peanuts subjects with primary hyperparathyroidism granulomatous diseases (sarcoidosis, tuberculosis, Wegner's granulomatosis) diabetes renal stones the last five years subjects seriously ill (or with chronic disease) and unfit for participation in the study (as judged by one of the study doctors) subjects using vitamin D supplements exceeding 800 IU per day or active vitamin D drugs (Rocaltrol or Etalpha) pregnancy

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 70 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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: vitamin D bolus<br>vitamin D 160 000 IU given as bolus | Drug: Vitamin D<br>* vitamin D given as bolus versus daily dosing<br>|
| Experimental: vitamin D daily<br>vitamin D 4000 IU daily for 28 days | Drug: Vitamin D<br>* vitamin D given as bolus versus daily dosing<br>|
| Placebo Comparator: placebo<br>identical looking as vitamin d | Drug: Placebo<br>* identical looking as vitamin D<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hepcidin change | Difference between vitamin D given as a bolus 160 000IU vs 4000 IU regarding change in serum hepcidin | 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference in serum PTH after 1 month | Difference between vitamin D given as a bolus 160 000IU vs 4000 IU regarding change in serum PTH, cathelicidin, RNA expression and micro RNA in peripheral blood, telomerase activity and the ratio between 1,25(OH)2D and 24,25(OH)2D, after 1 month | 4 weeks | 
| Difference in micro RNA Expression after 1 month | Difference between vitamin D given as a bolus 160 000IU vs 4000 IU | 4 weeks | 
| Difference in serum cathelicidin after 1 month | Difference between vitamin D given as a bolus 160 000IU vs 4000 IU | 4 weeks | 
| Difference in RNA Expression after 1 month | Difference between vitamin D given as a bolus 160 000IU vs 4000 IU | 4 weeks | 
| Difference in telomerase Activity after 1 month | Difference between vitamin D given as a bolus 160 000IU vs 4000 IU | 4 weeks | 
| Difference in ratio between 1,24(OH)2D and 24,24(OH)2D after 1 month | Difference between vitamin D given as a bolus 160 000IU vs 4000 IU | 4 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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vitamin D