The Efficacy of Denosumab to Reduce Osteoporosis After Spinal Cord Injury
试验速览
- 阶段
- 4 期
- 发起方
- 入组人数
- 24
- 试验地点
- 2
- 主要终点
- Bone mineral density (BMD) of the distal femur
研究概览
简要总结
Sublesional bone loss after acute spinal cord injury (SCI) is sudden, progressive, and dramatic. After depletion of bone mass and the loss of architectural integrity, it may be difficult, if even possible, to restore skeletal mass and strength. Denosumab is a relative new, highly potent anti-resorptive agent that has proven efficacy in postmenopausal osteoporosis to improve bone mass and in solid tumor patients to prevent a skeletal-related event to a greater extent than that with bisphosphonate administration. In persons with complete motor lesions, bisphosphonates have not been effective at reducing bone loss at the knee, the site of greatest relevance because of its increased risk of fracture. Anti-RANKL therapy appears to be more potent than bisphosphonates in animal models of bone loss due to immobilization, suggesting that treatment with denosumab may prove to be an efficacious therapy for persons with acute SCI to preserve bone mass and strength.
详细描述
The primary objective of this study is to test the efficacy of a potent anti-resorptive agent, denosumab [receptor activator of nuclear factor-κB ligand (RANKL) antibody; Amgen Inc.] to preserve bone mass at the hip and knee and trabecular connectivity at the knee after acute SCI. Setting: patient enrollment, study drug administration and DXA scanning will be completed at the Kessler Institute for Rehabilitation (KIR) and pQCT measurements will be performed at Columbia University. A Randomized, double-blind, placebo-controlled parallel group trial.
Twenty-four subjects with acute, motor complete SCI (≤12 weeks) who have been admitted to the Kessler Institute for Rehabilitation (KIR) will be recruited for participation. The age of study participation will be males between the ages of 18 and 65 years old and females between the ages of 18 and 50 years old. Primary outcome measure will be BMD as measured by DXA and microarchitecture as measured by pQCT at the hip and knee.
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
- Triple (Participant, 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
- •Complete motor SCI [American Spinal Injury Association Impairment Scale (AIS) grade A and B];
- •Duration of injury <12 weeks; and
- •Males between the ages of 18 and 65 years old and females between the ages of 18 and 50 years old.
排除标准
- •Extensive life-threatening injuries in addition to SCI;
- •Acute fracture or extensive bone trauma;
- •History of prior bone disease (Paget's hyperparathyroidism, osteoporosis, etc.)
- •Post menopausal women;
- •Men with known hypogonadism prior to SCI;
- •Anabolic or Steroid hormonal therapy; within the past year and longer than six months;
- •Hyperthyroidism;
- •Cushing's disease or syndrome;
- •Severe underlying chronic disease;
- •Heterotopic ossification of the knee region (HO limited to the hip region only will not exclude subject participation);
- •History of chronic alcohol abuse;
- •Diagnosis of Hypocalcemia;
- •Existing dental condition/dental infection
- •Any patient taking a bisphosphonate for heterotopic ossification (HO);
- •Current diagnosis of cancer or history of cancer; and
- •Any patient receiving moderate or high dose corticosteroids (>40 mg/d prednisone or an equivalent dose of other corticosteroid) for longer than one week, not including drug administered in an attempt to preserve neurological function at the time of acute SCI.
研究组 & 干预措施
Placebo
A group of participants will be randomized to the placebo group and will receive the identical volume of normal saline at parallel time points.
干预措施: Placebo (identical Denosumab volume of normal saline) (Drug)
Denosumab
A group of participants will be randomized to the experimental group and will have Denosumab (Prolia, 60 mg SC) administered at baseline, 6 and 12 months.
干预措施: Denosumab (Drug)
结局指标
主要结局
Bone mineral density (BMD) of the distal femur
时间窗: Baseline, 1, 3, 6, 12, and 18 months after Denosumab administration
Change in BMD at the distal femur will be obtained by dual energy X-ray absorptiometry (DXA) at baseline, 1, 3, 6, 12, and 18 months after Denosumab administration.
次要结局
- Bone microarchitecture of the distal femur and proximal tibia.(Baseline, 12, and 18 months after Denosumab administration)
研究者
William A. Bauman, M.D.
Director VA RR&D Center of Excellence for the Medical Consequences of SCI
James J. Peters Veterans Affairs Medical Center