Zoledronic Acid to Prevent Bone Loss After Acute Spinal Cord Injury
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 16
- 试验地点
- 1
- 主要终点
- Change in Areal Bone Mineral Density at Hip
研究概览
简要总结
Maintenance of bone mass following spinal cord injury (SCI) is essential to fracture prevention and the associated morbidity of bed rest and further secondary complications. Intravenous (IV) zoledronic acid (ZA) is an FDA-approved drug that has been shown to be more effective than other agents in reducing bone mass resorption and leg fractures in post-menopausal women, but has not been studied in patients with acute SCI. This will be a randomized, double-blind, placebo-controlled trial of IV ZA to prevent bone loss early after SCI. Up to 48 subjects will be randomized to receive a one-time dose of 5 mg of IV ZA versus placebo within 21 days of an SCI.
详细描述
Maintenance of bone mass following spinal cord injury (SCI) is essential to fracture prevention and the associated morbidity of bed rest and further secondary complications. Intravenous (IV) zoledronic acid (ZA) has been shown to be more effective than other agents in reducing bone mass resorption and fracture of the legs in post-menopausal women, but has not been studied in acute spinal cord injury. Two previous studies of ZA in persons with subacute SCI, while promising, were inconclusive. As stated in the long range plan of the National Institute on Disability and Rehabilitation Research (NIDRR), one goal in the area of health and function is to "focus on the onset of new conditions...exacerbation of existing conditions, or the development of coexisting conditions." This study is intended to demonstrate reduction in loss of bone mass at the hip and knee regions in acute SCI in a rigorous study of sufficient size to determine effectiveness of our intervention.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Ages 18-65, male or female
- •Traumatic SCI with Neurological level C4-T10, American Spinal Injury Association (ASIA) Impairment Scale (AIS) A,
- •Serum calcium level >7.0 mg/dL) at time of study drug administration
- •Screening baseline serum 25-hydroxy (25-OH) vitamin D of at least 13 ng/ml
- •No medical contraindication to supplemental vitamin D for participants whose levels are >13 ng/ml but sub-therapeutic (<32ng/ml)
- •No medical contraindication to supplemental calcium
- •Weight under 300 pounds, which is the maximum permitted on the dual-energy X-ray absorptiometry (DXA) scanner
排除标准
- •Ventilator-dependent individuals
- •Chronic steroid use (defined as >6 months)
- •Rheumatoid disease with use of prior disease modifying anti-rheumatic drugs (DMARDs) affecting bone density
- •History of osteoporosis or of treatment for osteopenia or osteoporosis with bisphosphonates, or selective reuptake estrogen modifying agents
- •Current use of medications* including bisphosphonates to treat osteoporosis (*note that prior calcium or vitamin D use is not an exclusion criteria)
- •History of more than one lower extremity osteoporosis-related fracture
- •Chronic renal insufficiency, creatinine clearance < 35 ml/min, during screening
- •End stage liver or kidney disease
- •Medical conditions resulting in hypogonadal states that affect bone density
- •Uncontrolled thyroid disease/thyrotoxicosis
- •Hereditary or acquired metabolic bone disorder
- •History of use of unfractionated heparin for >1 year
- •History of selected antiseizure medications, specifically phenobarbital, phenytoin, carbamazepine, sodium valproate >1 year
- •Acute or chronic bilateral lower extremity fractures involving tibia or femur, with placement of surgical hardware in any areas of above locations
- •Severe hypotension requiring use of intravenous blood pressure agents such as dopamine, norepinephrine or phenylephrine. Exception may allow for patients on pressors who arm experiencing hypotension as they acclimate to upright posture.
- •Inability to provide informed consent and understand the consent process
- •Facial fractures requiring oral surgery
- •Dental surgery or oral maxillofacial surgery within 2 weeks of anticipated study drug administration
- •Pregnancy present on admission
- •Vitamin D deficiency on admission testing (serum 25-OH D reported as < 13 ng/mL)
- •Patients with an established reaction to, or history of, anaphylactic shock to aspirin
研究组 & 干预措施
Zoledronic Acid 5 mg IV infusion
Single infusion of 5 mg intravenous zoledronic acid given within 21 days of acute traumatic spinal cord injury.
干预措施: Zoledronic acid (Drug)
normal saline 0.9%
Infusion of normal saline of equivalent volume to reconstituted zoledronic acid, given only once and run over 2 hours, to occur within 21 days of acute traumatic spinal cord injury.
干预措施: normal saline 0.9% (Drug)
结局指标
主要结局
Change in Areal Bone Mineral Density at Hip
时间窗: one year
Percent change in areal bone mineral density (aBMD) assessed by dual energy X-ray absorptiometry (DXA) at 12 months post-injury compared to baseline. This will compare aBMD at the hip.
Change in Areal Bone Mineral Density at Knee
时间窗: one year
Percent change in areal bone mineral density (aBMD) assessed by dual energy X-ray absorptiometry (DXA) at 12 months post-injury compared to baseline. This will compare aBMD at the distal femur and proximal tibia.
次要结局
- Change in Biomarkers of Bone Resorption (sCTX)(1 month, 4 months, 12 months)
- Safety and Tolerability of Zoledronic Acid(72-hours and 1 month post intervention.)
- Change in Biomarkers of Bone Formation (P1NP)(1 month, 4 months)