Treatment With Romosozumab Versus Denosumab to Improve Bone Mineral Density and Architecture in Subacute SCI

Study Overview
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Brief Summary
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The objective of the proposed work is to determine whether administration for 12 months of romosozumab followed by 12 months of denosumab will maintain bone mass at the knee in subjects with subacute SCI compared to 24 months of denosumab administration alone.

Official Title
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Treatment With Romosozumab Versus Denosumab to Improve Bone Mineral Density and Architecture in Subacute SCI

Conditions
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Osteoporosis, Spinal Cord Injuries

Intervention / Treatment
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* Drug: Romosozumab
* Drug: Denosumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Traumatic motor-complete or incomplete SCI C4-L2 (AIS grade A-C); Duration of SCI less than 6 months; Males and females (premenopausal) between the ages of 18 and 55 years old; and a safe range of BMD right above the knee as determined by study staff review; Exclusion Criteria: Active and/or history of coronary heart disease or stroke; Bone cancer; Long-bone fracture of the leg within the past year; History of prior bone disease (for example, Paget's hyperparathyroidism, osteoporosis, etc.); Postmenopausal women; Men with known low functioning tests before SCI; Drugs geared toward increasing BMD longer than a six month duration after SCI; As determined by study staff review of my medication history of glucocorticoid administration longer than three months duration within the last year Abnormalities of my endocrine glands such as hyperthyroidism, Cushing's disease or syndrome, etc.; Severe underlying chronic disease (for example chronic obstructive pulmonary disease (COPD), end-stage heart disease, chronic renal failure); Heterotopic ossification (HO) of the distal femur (the knee end of the thigh bone). HO is a condition where bone tissue forms outside of the skeleton. If HO is found in any other area than the distal femur it will not prevent my participation in the study.; History of chronic alcohol abuse; Diagnosis of hypercalcemia (high levels of calcium in the blood); Pregnancy; As determined by study staff review of my medications a bisphosphonate for heterotopic ossification (HO), or other medications to treat osteoporosis other than calcium and vitamin D; Current diagnosis of cancer or history of cancer; As determined by study staff review of my medications, prescribed moderate or high dose corticosteroids (>40 mg/d prednisone or an equivalent dose of other corticosteroid medication) for longer than one week, not including drug administered to preserve neurological function at the time of acute SCI; and Life expectancy less than 5 years.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Arm 1: romosozumab administered monthly from baseline to month 11 followed by denosumab at month 12 and 18. Arm 2: denosumab administered at baseline, month 6, 12, and 18
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Romosozumab Baseline to Month 11 followed by Denosumab Month 12 to Month 24<br>Of the forty (40) individuals with subacute spinal cord injury (SCI) enrolled in this study, twenty (20) participants will be randomly selected to receive romosozumab (210mg SQ) once a month for 12 months. After 12 months the same twenty (20) individuals will receive denosumab (60mg SQ) at month 12 and 18. | Drug: Romosozumab<br>* Romosozumab (Amgen Inc., Thousand Oaks, CA) 210mg SQ administered each month<br>* Other names: Evenity;Drug: Denosumab<br>* Denosumab (Amgen Inc., Thousand Oaks, CA) 60 mg SQ administered every six months<br>* Other names: Prolia;|
| Active Comparator: Denosumab Baseline to Month 24<br>Of the forty (40) individuals with subacute spinal cord injury (SCI) enrolled in this study, twenty (20) participants will be randomly selected to receive denosumab (60 mg SQ) at baseline and 6, 12, and 18 months. | Drug: Denosumab<br>* Denosumab (Amgen Inc., Thousand Oaks, CA) 60 mg SQ administered every six 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 metaphysis | BMD at the distal femur metaphysis will be obtained by dual energy X-ray absorptiometry (DXA) | Baseline to 24 months | 

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