Clinical Approaches to Correcting Vitamin D Inadequacy and Maintaining Adequacy

Study Overview
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Brief Summary
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Vitamin D is available in two forms, vitamin D2 and vitamin D3. It has previously been assumed that these two forms maintain blood vitamin D equally. However, this may not be the case. This study will evaluate whether D2 and D3 produce equal elevation of blood vitamin D. Additionally, it will evaluate whether once per month vitamin D dosing is as effective in maintaining blood vitamin D levels as daily dosing.

Official Title
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Clinical Approaches to Correcting Vitamin D Inadequacy and Maintaining Adequacy

Conditions
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Vitamin D Inadequacy, Vitamin D Deficiency

Intervention / Treatment
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* Dietary Supplement: Cholecalciferol (vitamin D3)
* Dietary Supplement: Ergocalciferol (vitamin D2)
* Dietary Supplement: Ergocalciferol (vitamin D2)
* Dietary Supplement: Cholecalciferol (vitamin D3)
* Dietary Supplement: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Community dwelling men and women age ≥ 65 years. Able and willing to sign informed consent. Serum 25OHD concentration ≥ 10 and less than 60 ng/ml by HPLC. Willing to avoid use of cod-liver oil and non-study vitamin D supplementation; standard multiple vitamins containing ≤ 400 IU used no more than once daily will be allowed Exclusion Criteria: Current hypercalcemia (serum calcium > 10.5 mg/dl) or untreated primary hyperparathyroidism. History of nephrolithiasis. Screening 25OHD concentration ≥ 60 ng/ml. Baseline 24-hour urine calcium > 250 mg if female, > 300 mg if male. Known risk factors for hypercalcemia, e.g., malignancy, tuberculosis, sarcoidosis, Paget's disease History of any form of cancer within the past five years with the exception of adequately treated squamous cell or basal cell skin cancer. Renal failure defined as a calculated creatinine clearance (Cockroft-Gault method) ≤ 25 ml/minute Severe end-organ disease, e.g., cardiovascular, hepatic, hematologic, pulmonary, etc., which may limit ability to complete the study Known malabsorption syndromes, e.g., celiac disease, radiation enteritis, active inflammatory bowel disease, etc. Use of medications known to alter bone turnover including bisphosphonates, estrogen, selective estrogen receptor modulators, PTH, testosterone or calcitonin Vitamin D intake greater than 5,000 IU daily Treatment with any active metabolites of vitamin D within six months of screening Treatment with any drug which may interfere with vitamin D metabolism, e.g., phenobarbital, phenytoin.

Ages Eligible for Study
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Minimum Age: 65 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br> | Dietary Supplement: Ergocalciferol (vitamin D2)<br>* oral capsule 50,000 IU once monthly for 12 months<br>Dietary Supplement: Placebo<br>* oral placebo capsule once daily for 12 months<br>|
| Experimental: 2<br> | Dietary Supplement: Ergocalciferol (vitamin D2)<br>* oral capsule 1600 IU once daily for 12 months<br>Dietary Supplement: Placebo<br>* oral placebo capsule once daily for 12 months<br>|
| Experimental: 3<br> | Dietary Supplement: Cholecalciferol (vitamin D3)<br>* 50,000 IU once monthly for 12 months<br>Dietary Supplement: Placebo<br>* oral placebo capsule once daily for 12 months<br>|
| Experimental: 4<br> | Dietary Supplement: Cholecalciferol (vitamin D3)<br>* oral capsule 1600 IU once daily for 12 months<br>Dietary Supplement: Placebo<br>* oral placebo capsule once daily for 12 months<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The primary outcome measure is change in 25OHD with various D2 and D3 dosing regimens. |  | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine whether once monthly vitamin D2 or D3 dosing is as effective as daily dosing in attainment, and subsequent maintenance, of 25OHD status |  | 12 months | 
| Delineate the effect of these vitamin D regimens on other parameters of skeletal relevance |  | 12 months |