A Multi-centre, Prospective, Randomised Trial of Short Course Alendronate Therapy or Placebo Combined With Vitamin D and Calcium to Prevent Loss of Bone Mineral Density in Antiretroviral-naïve, HIV-1 Infected Subjects Initiating Antiretroviral Therapy
试验速览
- 阶段
- 4 期
- 状态
- 终止
- 入组人数
- 53
- 试验地点
- 2
- 主要终点
- Rate of changes in bone mineral density
研究概览
简要总结
Antiretroviral therapy (ART) initiation is associated with a significant loss of bone mineral density (BMD), characterised by increases in bone turnover, which is largely limited to the first 48 weeks of therapy. Bisphosphonates, such as alendronate, decrease bone turnover and can limit loss of bone mineral density.
This study aims to determine if a short course of treatment with the oral bisphosphonate alendronate can limit loss of bone mineral density associated with initiation of ART in HIV-1 infected, antiretroviral naive, adult subjects.
详细描述
Multi-centre, prospective, randomised, double-blind, placebo-controlled trial over 50 weeks. The aims of this study include:
- To determine if short-course treatment with alendronate versus placebo combined with calcium and vitamin D, initiated 2 weeks prior to start of ART and can prevent loss of BMD over 48 weeks of follow-up post ART initiation.
- To explore the effect of alendronate on bone turnover in the setting of ART initiation.
- To determine which factors, such as choice of ART, impacts the protective effect of alendronate in preventing BMD loss.
- To determine the relationship between changes in bone turnover markers, vitamin D, parathyroid hormone and calcium levels.
- To explore the pathogenesis of BMD loss with initiation of ART by investigating relationships between changes in immune function (T-cells and B-cells subsets), bone turnover and BMD.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 30 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •male>30 years old or female>35 years old
- •HIV-1 antibody positive
- •antiretroviral therapy naïve
- •be presumed to have achieved peak bone mass
- •be eligible for initiation of antiretroviral therapy in the opinion of the investigator
- •be able to provide written, informed consent
排除标准
- •subjects unable to comply with the study protocol or unable to stand/sit upright for at least 30 minutes
- •history of osteoporosis
- •history of fragility fracture or previous femoral fracture
- •chronic renal failure
- •hypocalcemia or hypercalcemia at screening
- •history of Paget's disease or known primary hyperparathyroidism
- •previous treatment with or allergy (including hypersensitivity) to bisphosphonates
- •recent history (past 12 months) of peptic or duodenal ulcers or oesophagitis, aspiration or any other abnormality of the oesophagus
- •current therapy with prescribed calcium or vitamin D preparations (other than over-the-counter multivitamin preparations)
- •current therapy with aspirin or other regularly prescribed non-steroidal anti-inflammatory drugs
- •recent dental work (within the past 3 months) or poor oral hygiene (as judged in the opinion of the investigator)
- •recent (within the past three months) significant steroid exposure
- •for female subjects: pregnancy at screening, planning future pregnancies or unwilling to take measures to avoid pregnancy for the duration of the study
- •where in the investigator's opinion, there is a necessity to initiate ART within the pre-ART study window period
- •hepatitis B or hepatitis C co-infection
- •any active illness (including AIDS illness) which in the opinion of the investigator precludes participation in the study
- •subjects concurrently enrolled in another clinical trial of an investigational medical product
研究组 & 干预措施
Alendronate
Alendronate 70 mg plus calcium/vitamin D (1250 mg/400iu) plus Truvada®
干预措施: Alendronate (Drug)
Alendronate
Alendronate 70 mg plus calcium/vitamin D (1250 mg/400iu) plus Truvada®
干预措施: calcium carbonate and colecalciferol (Dietary Supplement)
Alendronate
Alendronate 70 mg plus calcium/vitamin D (1250 mg/400iu) plus Truvada®
干预措施: Tenofovir disoproxil (Drug)
Placebo
Placebo to alendronate 70mg plus calcium/vitamin D (1250 mg/400iu) plus Truvada®
干预措施: Placebo (Drug)
Placebo
Placebo to alendronate 70mg plus calcium/vitamin D (1250 mg/400iu) plus Truvada®
干预措施: calcium carbonate and colecalciferol (Dietary Supplement)
Placebo
Placebo to alendronate 70mg plus calcium/vitamin D (1250 mg/400iu) plus Truvada®
干预措施: Tenofovir disoproxil (Drug)
结局指标
主要结局
Rate of changes in bone mineral density
时间窗: 50 weeks
Between-group differences in percentage change in total hip, lumbar spine, femoral neck BMD and body composition to week 50 among subjects who received at least one dose of the study medication
次要结局
- Rate of changes in bone turnover markers(50 weeks)
- Impact of ART choice on alendronate protective effect(50 weeks)
研究者
Patrick Mallon
Principal Investigator
University College Dublin