Randomized Double-blind Study Investigating Dose-dependent Longitudinal Effects of Vitamin D Supplementation on Bone Health
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 311
- 试验地点
- 2
- 主要终点
- Bone strength, as estimated by Finite Element Analysis of High Resolution peripheral Quantitative Computed Tomography (HR-pQCT) measurements at the distal radius and tibia
研究概览
简要总结
We propose to conduct a randomized double blind trial of three doses of vitamin D, 400, 4000, and 10,000 International Units (IU) per day, to assess the effect on bone density and architecture as assessed by high resolution peripheral quantitative tomography (HR-pQCT) measurements at the radius and distal tibia, and standard Dual X-ray absorptiometry (DXA). Other measures of bone and calcium metabolism will be assessed. The trial will last as long as three years. Approximately 300 healthy men and women, aged 50-70 years of age, will be recruited, and randomly assigned to one of the three doses of vitamin D. Other outcome variables assessed include quality of life, depression, muscle strength and balance.
详细描述
Hypotheses being tested:
- It is hypothesized that vitamin D, in a dose-dependent manner, will suppress parathyroid hormone action, resulting in less bone turnover, and decreased cortical porosity, leading to improved bone strength as assessed by finite element analysis.
- It is hypothesized that vitamin D, in a dose-dependent manner, will increase bone density in the central skeleton (spine, hip), as measured by the current standard method of dual X-ray absorptiometry (DXA).
- It is hypothesized that vitamin D, in a dose-dependent manner, will have an impact on quality of life, including indices of depression, as measured by the SF-36 questionnaire and an appropriate index of depression.
Outcomes:
Primary outcomes:
- (1) bone density and (2) strength as measured by HR-pQCT
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 55 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy women and men between 55 and 70 years of age; women will be at least 5 years post-menopause. Presence of a chronic illness does not exclude participation if the condition is stable and managed by a physician.
- •Baseline lumbar spine and total hip bone mineral density (BMD) T-score above 2.5 as assessed using dual x-ray absorptiometry (DXA).
排除标准
- •A serum 25-[OH] vitamin D (25OHD) of <30 nmol/L (<12 ng/mL) or >125 nmol/L (50 ng/mL).
- •Hypercalcemia (serum calcium >2.55 mmol/L), hypocalcemia (serum calcium <2.10 mmol/L) or eGFR <30 mL/min.
- •Surgical cure of Primary Hyperparathyroidism within the last year.
- •Active kidney stone disease (recurrent stones, recent kidney stone [within last 2 years])
- •Known hypersensitivity or allergy to Vitamin D
- •Serum creatinine, AST, ALT, PTH, calcium, or alkaline phosphatase greater than 1.5 times the upper limit of normal at the screening visit
- •BMD exclusions:
- •High 10-year risk for osteoporotic fracture, as defined by the Canadian Association of Radiologists/Osteoporosis Canada calculator, or the World Health Organization's FRAX calculator.
- •DXA T-score below or equal to -2.5 SD.
- •Have taken bone active osteoporosis prescription drugs in the past 2 years (bisphosphonates) or 1 year (other osteoporosis prescription therapies).
- •Any medical condition that would prevent participation in a clinical trial for a full three years.
- •Medications such as prednisone >2.5 mg daily (or equivalent); other bone active medications such as tamoxifen or aromatase inhibitors for breast cancer, or androgen deprivation therapy of prostate cancer.
- •Disorders known to affect vitamin D metabolism such as sarcoidosis or renal failure or malabsorption disorders (e.g. pancreatic insufficiency or celiac disease).
- •Regular (monthly or more frequent) use of tanning salons.
研究组 & 干预措施
vitamin D 10,000 IU
Subjects in this arm receive 10,000 IU Vitamin D p.o. (as 5 drops of a blinded vitamin D solution) per day. Duration: 3 years
干预措施: Vitamin D (Dietary Supplement)
Vitamin D 4000 IU
Subjects in this arm receive 4,000 IU Vitamin D p.o. (as 5 drops of a blinded vitamin D solution) per day. Duration: 3 years
干预措施: Vitamin D (Dietary Supplement)
Vitamin D 400 IU
Subjects in this arm receive 400 IU Vitamin D p.o. (as 5 drops of a blinded vitamin D solution) per day. Duration: 3 years
干预措施: Vitamin D (Dietary Supplement)
结局指标
主要结局
Bone strength, as estimated by Finite Element Analysis of High Resolution peripheral Quantitative Computed Tomography (HR-pQCT) measurements at the distal radius and tibia
时间窗: Participants will be followed from baseline up to 36 months
HR-pQCT scans provide the ability to measure a true volumetric density of the bone region of interest and to study microarchitecture of both trabecular and cortical bone, from which an assessment of strength by Finite Element Analysis (FEA) can be determined: briefly, a 3-dimensional computer model of bone can be constructed from the HR-pQCT data, and subjected to strength testing. FEA software (FAIM, version 6.0, Numerics88 Solutions, Calgary, Canada) is used to estimate failure load (N) based on 2 % of the elements exceeding 7,000 μstrain. The analysis examines change from baseline measured at 6, 12, 24, and 36 months.
Total Bone Mineral Density (Tt.BMD) at the distal radius and tibia, as measured by High Resolution peripheral Quantitative Tomography (HR-pQCT)
时间窗: Participants will be followed from baseline up to 36 months
Unlike the measurement of bone density by DXA (a secondary outcome, see below), which estimates bone density based on assumptions of the depth of a 2-dimensional image of bone, HR-pQCT measurement of Tt.BMD provides a true volume based density measurement. HR-pQCT also provides a much higher resolution image of the region of interest than the image derived from a DXA measurement. Units of this measurement are milligrams hydroxyapatite per cubic centimetre (mg HA/cm3). The analysis will examine change in Tt.BMD at distal radius and tibia from baseline to measurements at 6, 12, 24, and 36 months.
次要结局
- Cortical bone density (Ct.BMD) of bone as measured by HR-pQCT(From baseline to 36 months - measured at 0, 6, 12, 24, and 36 months.)
- Cortical Porosity (Ct.Po) of bone as measured by HR-pQCT(From baseline to 36 months - measured at 0, 6, 12, 24, and 36 months.)
- Trabecular number (Tb.N) as measured by HR-pQCT(From baseline to 36 months - measured at 0, 6, 12, 24, and 36 months.)
- Trabecular bone density (Tb.BMD) of bone as measured by HR-pQCT(From baseline to 36 months - measured at 0, 6, 12, 24, and 36 months.)
- Bone Mineral Density as measured by Dual X-ray Absorptiometry(Participants will be followed from baseline up to 36 months)
- Quality of Life (Mental Health Component)(Participants will be followed from baseline up to 36 months)
- Biochemical markers of calcium and bone metabolism(Participants will be followed from baseline up to 36 months)
- Depression symptoms(Participants will be followed from baseline up to 36 months)
- Balance and grip strength(Participants will be followed from baseline up to 36 months)
研究者
David A. Hanley, MD, FRCPC
Professor Emeritus, Department of Medicine
University of Calgary