Change in Free 25(OH)D After High Dose in Vitamin D Deficient Postmenopausal Women
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 112
- 试验地点
- 2
- 主要终点
- Free 25(OH)D
研究概览
简要总结
Total 25(OH)D is currently used as a biomarker of vitamin D status. However, there is some debate as to whether total 25(OH)D is the best marker to use.
It has been suggested that free vitamin D may be better because it may be more biologically available.
There are also some uncertainties about how we treat vitamin D deficiency. A single dose is attractive because it is certain that the patient has had the dose and there is no requirement for ongoing compliance, but it is still not clear what the best dose is to give. Also, recent studies have highlighted that high dose vitamin D supplementation may increase the risk of falling in older populations.
The investigators believe that studying how free vitamin D responds to different bolus doses is the best way address some of the current research gaps, including what is the best biomarker of vitamin D status, what is the mechanism of vitamin D toxicity and what is a safe bolus dose to treat deficiency.
The investigators will study changes in total and free 25(OH)D, and also clinical response, to three different bolus doses of vitamin D (50 000IU, 150 000IU and 500 000IU) in 84 vitamin D deficient postmenopausal women, over a three month period with 5 study visits. A concurrent control group of 28 vitamin D sufficient postmenopausal women will also be recruited.
This will allow the investigators to determine how total and free vitamin D change with bolus dosing and whether there is a disproportionate rise in free 25(OH)D with higher doses that may lead to hypercalcemia and falls.
详细描述
The most commonly used measurement of vitamin D status is serum 25-hydroxyvitamin D (25(OH)D). However there is no clear consensus on the level of 25(OH)D required to protect against adverse effects of deficiency.
One approach is to define deficiency is the level of 25(OH)D at which there is a secondary physiological response, such as a rise in parathyroid hormone. However, this approach has not yielded a clear answer. Total 25(OH)D below 30nmol/l is not always associated with an increased parathyroid hormone (PTH) response, and total 25(OH)D and PTH do not always respond to vitamin D supplementation. This suggests that total 25(OH)D measurement may not be the best biological marker of vitamin D status.
Vitamin D and its metabolites are bound to proteins in the circulation: around 85-90% of 25(OH)D is bound to vitamin D binding protein (DBP), 10-15% is bound to albumin, and less than 1% is in the free form. DBP protects 25(OH)D from degradation and allows a circulating store to accumulate.
The free hormone hypothesis suggests that only the unbound 'free' portion of protein bound hormones is biologically active, and that this should be measured for the accurate assessment of hormone availability. Calculated free 25(OH)D concentrations have been shown to be better correlated to bone mineral density (BMD) than total 25(OH)D in a healthy population and to be more closely related to PTH in patients with end stage renal disease.
The binding capacity of DBP may be overwhelmed in some situations. In female participants treated with an oral dose of 500,000 IU annually for 3 years there was an increase in the risk of falls and fractures that was particularly marked in the three month period after each dose. It has been proposed that there was vitamin D toxicity and possible hypercalcaemia during this period due to the binding capacity of DBP being overwhelmed by the large increase in 25(OH)D with a relatively greater increase in free 25(OH)D. However, free vitamin D and calcium were not measured in the study, so there is not yet evidence to support this hypothesis.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 55 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •Caucasian
- •25(OH)D < 30nmol/l for treatment groups or 25(OH)D >50nmol/l for control group
- •BMI between 20 kg/m2 and 30kg/m2
- •55 years and over and postmenopausal (at least 5 years since last menstrual period)
- •Able and willing to participate in the study and provide written informed consent.
排除标准
- •History of any long term immobilization (duration greater than three months)
- •Pre-diagnosed diabetes mellitus
- •High trauma fracture or low trauma fracture less than one year prior to recruitment
- •History of or current conditions known to affect vitamin D or bone metabolism, including:
- •Chronic renal disease Malabsorption syndromes Diagnosed endocrine disorders Hypercalcaemia Diagnosed restrictive eating disorder
- •Use of medications or treatment known to affect vitamin D or bone metabolism such as bisphosphonates or anti-epileptic medication.
- •Alcohol intake of greater than 21 units per week
- •Holiday with significant sunlight exposure in the last six weeks
- •Planned sun holiday within study period
- •Abnormal clinical laboratory parameters that are assessed as clinically significant by the PI.
研究组 & 干预措施
50 000IU Vitamin D3
50 000IU oral vitamin D3 (cholecalciferol) administered at baseline only.
干预措施: Cholecalciferol (Vitamin D3) (Dietary Supplement)
150 000IU Vitamin D3
150 000IU oral vitamin D3 (cholecalciferol) administered at baseline only.
干预措施: Cholecalciferol (Vitamin D3) (Dietary Supplement)
500 000IU Vitamin D3
500 000IU oral vitamin D3 (cholecalciferol) administered at baseline only.
干预措施: Cholecalciferol (Vitamin D3) (Dietary Supplement)
Concurrent Control
Control group to receive no intervention.
结局指标
主要结局
Free 25(OH)D
时间窗: Baseline to visit 3 (5-7 days after administration)
Change in free 25(OH)D from baseline to visit 3 (5-7 days after administration)
次要结局
- Proportion of total 25(OH)D to free 25(OH)D(5(+/-2) days, 28(+/-3) days and 84(+/-5) days)
- 1, 25(OH)2D(5(+/-2) days, 28(+/-3) days and 84(+/-5) days)
- Ionized calcium(5(+/-2) days, 28(+/-3) days and 84(+/-5) days)
- Parathyroid Hormone(5(+/-2) days, 28(+/-3) days and 84(+/-5) days)
- Bone turnover marker - Alkaline Phosphatase(5(+/-2) days, 28(+/-3) days and 84(+/-5) days)
- Bone turnover marker - CTX(5(+/-2) days, 28(+/-3) days and 84(+/-5) days)
- Bone turnover marker - PINP(5(+/-2) days, 28(+/-3) days and 84(+/-5) days)
- Repeated chair stand test score(5(+/-2) days, 28(+/-3) days and 84(+/-5) days)
- Tandem stand balance test score(5(+/-2) days, 28(+/-3) days and 84(+/-5) days)
- 8-feet walk course test score(5(+/-2) days, 28(+/-3) days and 84(+/-5) days)
- Laying blood pressure(5(+/-2) days, 28(+/-3) days and 84(+/-5) days)
- Standing blood pressure(5(+/-2) days, 28(+/-3) days and 84(+/-5) days)
- Bone turnover marker - Osteocalcin(5(+/-2) days, 28(+/-3) days and 84(+/-5) days)