Denosumab Administration After Spinal Cord Injury

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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The Efficacy of Denosumab to Reduce Osteoporosis After Spinal Cord Injury

Conditions
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Osteoporosis, Spinal Cord Injury

Intervention / Treatment
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* Drug: Denosumab
* Drug: Placebo (identical Denosumab volume of normal saline)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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. Exclusion Criteria: 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; Pregnancy; 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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>A group of participants will be randomized to the placebo group and will receive the identical volume of normal saline at parallel time points. | Drug: Placebo (identical Denosumab volume of normal saline)<br>* The placebo group will receive the identical volume of normal saline at parallel time points.<br>* Other names: Unknown at this time;|
| Experimental: Denosumab<br>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. | Drug: Denosumab<br>* In clinical trials, denosumab (Amgen Inc., Thousand Oaks, CA), has been shown to be more potent in reducing osteoclastosis and function than bisphosphonates.39,40 The rate of bone loss in the lower extremity at sites of interest in patients with acute SCI has been reported to be several-fold greater than the rate of bone loss in postmenopausal women not prescribed antiresorptive medications, which is about 3-5% per year.11,50,51 The dose of denosumab chosen for our protocol in patients after acute SCI will be the same dose that has been shown to be efficacious to treat postmenopausal osteoporosis (60 mg SQ q 6 months).<br>* Other names: Prolia;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Bone mineral density (BMD) of the distal femur | 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. | Baseline, 1, 3, 6, 12, and 18 months after Denosumab administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Bone microarchitecture of the distal femur and proximal tibia. | Change in microarchitecture at the distal femur and proximal tibia will be obtained by peripheral quantitative computerized tomography (pQCT) at baseline, 12, and 18 months after Denosumab administration. | Baseline, 12, and 18 months after Denosumab administration | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Spinal Cord Injury, Denosumab, Osteoporosis, Dual Energy X-ray Absorptiometry