Treatment of Vitamin D Insufficiency

Study Overview
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Brief Summary
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The purpose of this study is to answer the following questions: Does vitamin D increase calcium absorption, bone mass and muscle mass and function in women past menopause who have mildly low vitamin D levels? Do these benefits require prescription-strength vitamin D, or is an over the counter vitamin D dose enough?

Detailed Description
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Osteoporosis is a major health problem in postmenopausal women. At age 50, half of women will suffer an osteoporotic fracture in their remaining lifetime, causing increased disability and mortality. Vitamin D deficiency, defined as a serum 25(OH)D <15 ng/mL, contributes to osteoporosis via decreased calcium absorption (Ca·Ab), secondary hyperparathyroidism (HPT), increased bone resorption and decreased bone mineral density (BMD). Thus, experts agree that patients with vitamin D deficiency should receive vitamin D therapy. Vitamin D insufficiency (VDI) is a milder form of hypovitaminosis D defined as a 25(OH)D level between 15 and 30 ng/mL regardless of parathyroid hormone (PTH) status. Experts disagree on whether to treat VDI, as the clinical benefits of therapy are uncertain. Some experts insist the optimal 25(OH)D level is ≥30 ng/mL. By contrast, both the Food and Nutrition Board and NIH Evidence Report No. 158 state that insufficient evidence exists to declare the optimal serum 25(OH)D for bone health, despite review of  170 studies. Consequently, the Food and Nutrition Board cannot determine a recommended daily allowance for vitamin D. Confusion over the optimal 25(OH)D level results, in part, because previous trials failed to recruit subjects based on initial 25(OH)D levels and/or failed to target or achieve 25(OH)D levels ≥30 ng/mL. Moreover, secondary HPT, the proposed mechanism by which VDI causes bone loss, occurs in only 10% to 33% of people with VDI. As such, people with VDI and normal PTH might not experience clinical benefits from vitamin D therapy. VDI is widespread, affecting 26% to 39% of postmenopausal American women with and without osteoporosis. Therefore, determining the ideal 25(OH)D level for optimal calcium homeostasis and bone health is of utmost clinical and public health importance. Our overall goal, congruent with Healthy People 2010 objective 2-9, is to evaluate the effect of vitamin D therapy on the risk of osteoporosis in postmenopausal women with VDI, as reflected by changes in Ca·Ab, BMD and muscle fitness. Our second goal is to evaluate whether a high-dose vitamin D regimen, chosen to achieve and maintain a 25(OH)D level ≥30 ng/mL, is superior in its effects on study outcomes compared to a low-dose vitamin D regimen that can permit continued VDI. We will conduct a randomized, placebo-controlled double-blind trial of low-dose and high-dose vitamin D in postmenopausal women with vitamin D insufficiency in order to investigate the following aims: To evaluate the effect of vitamin D3 therapy on Ca·Ab in postmenopausal women less than or equal to 75 years old with VDI. Sub-aims include the investigation of subject variables influencing Ca·Ab and 25(OH)D levels at baseline and one month, the accuracy of oral isotope plasma levels for Ca·Ab measurement and the ability of a questionnaire to identify patients with low vitamin D status. To evaluate the effects of vitamin D3 therapy on the 12-month change in BMD and bone turnover in the same trial conducted for Aim 1. Sub-aims include the identification of subject variables significantly influencing change in BMD and an evaluation of the relationship between changes in Ca·Ab and changes in BMD. To evaluate the effect of vitamin D therapy on muscle mass and functional capacity in the same trial conducted for Aim 1. We will measure muscle mass by whole body bone densitometry and assess muscle function using the Timed Up and Go (TUG) Test and the modified Stanford Health Assessment Questionnaire (HAQ) score. Sub-aims include the identification of subject variables significantly influencing muscle outcomes.

Official Title
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Treatment of Vitamin D Insufficiency

Conditions
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Vitamin D Deficiency

Intervention / Treatment
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* Dietary Supplement: High Dose Vitamin D3
* Dietary Supplement: Low Dose Vitamin D3
* Dietary Supplement: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Vitamin D insufficiency, defined as a serum 25(OH)D 16 to 25 ng/mL by high performance liquid chromotography assay Women ≥ 5 years past the date of last menses or bilateral oophorectomy, or ≥ 60 years old if they had prior hysterectomy without bilateral oophorectomy Total dietary and supplemental calcium intake < 600 mg daily but ≤ 1,400 mg daily, based on a food frequency questionnaire Exclusion Criteria: Women > 75 years old Hypercalcemia (serum calcium corrected for albumin > 10.4 mg/dL) Nephrolithiasis by medical record or patient report Inflammatory bowel disease, malabsorption or chronic diarrhea Stage 3, 4 or 5 Chronic Kidney Disease based on the Modification of Renal Diet (MDRD) formula Use of bone-active medications within the past 6 months including bisphosphonates, estrogen compounds, calcitonin, teriparatide, oral corticosteroids and anticonvulsants Allergy or intolerance to orange juice Allergy or intolerance to sunscreen Prior adult clinical fragility fracture of the hip, spine or wrist or a T-score below -2.5 at the lumbar spine or femur

Ages Eligible for Study
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Maximum Age: 75 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: High Dose Vitamin D3<br>Loading Dose: 50,000 International Units vitamin D3 gel-caps (yellow) to take daily for 15 days and placebo gel-caps (white) to take daily for 15 days. Maintenance Dose: 50,000 International Units vitamin D3 gel-caps (yellow) to take two times a month for 350 days and placebo gel-caps (white) to take daily for 350 days. | Dietary Supplement: High Dose Vitamin D3<br>* Yellow gel-cap vitamin D3 at 50,000 International Units daily for 15 days then two times a month for 350 days. Daily white placebo pills.<br>* Other names: Cholecalciferol;|
| Other: Low Dose Vitamin D3<br>Loading Dose: 800 International Units vitamin D3 gel-caps (white) to take daily for 15 days plus placebo gel-caps (yellow) to take daily for 15 days. Maintenance Dose: 800 International Units vitamin D3 gel-caps (white) to take daily for 350 days plus placebo gel-caps (yellow) to take two times a month for 350 days. | Dietary Supplement: Low Dose Vitamin D3<br>* White gel-cap vitamin D3 at 800 International Units to take orally, daily for 365 days. Intermittent yellow placebo pills.<br>* Other names: Cholecalciferol;|
| Placebo Comparator: Placebo<br>Loading Dose: Placebo gel-caps (yellow) to take daily for 15 days plus placebo gel-caps (white) to take daily for 15 days. Maintenance Dose: Placebo gel-caps (yellow) to take two times a month for 350 days plus placebo gel-caps (white) to take daily for 350 days. | Dietary Supplement: Placebo<br>* Yellow gel-cap placebo pills to take orally, daily for 15 days then two times a month for 350 days. White gel-cap placebo pills once daily for 365 days.<br>* Other names: sugar pill;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Intestinal Calcium Absorption | Percent of calcium absorbed in the intestinal tract within one day | One Year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Bone Mineral Density | Annualized percent change in bone mineral density at spine, hip, femoral neck, and body | 1 Year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Vitamin D, Cholecalciferol, Parathyroid Hormone, Calcium Absorption, Bone Mineral Density, Muscle Function