Prevention of Bone Loss After Acute SCI by Zoledronic Acid

Study Overview
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Brief Summary
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The overall objective of this study is to define an effective therapeutic approach, using currently available medication, to prevent or mitigate the loss of bone mass and bone strength that occurs after acute spinal cord injury.

Detailed Description
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This is a randomized, double-blind placebo-controlled study of zoledronic acid to evaluate its efficacy and safety over a 2 year period for the prevention of bone loss and maintenance of bone strength in individuals with recent onset SCI (see diagram below). Subjects will be randomized at the baseline visit to receive either zoledronic acid or placebo. At the end of the first year of the study, each treatment group will be re-randomized to either zoledronic acid or placebo to evaluate the durability of response to zoledronic acid and the utility of serum bone markers to guide therapeutic decision making. DXA imaging, CT imaging and bone markers will be obtained at baseline, 3 months, 6 months, 12 months, 18 months and 24 months.

Official Title
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Prevention of Bone Loss After Acute SCI by Zoledronic Acid: Durability, Effect on Bone Strength, and Use of Biomarkers to Guide Therapy

Conditions
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Spinal Cord Injury, Acute Spinal Cord Injury, Bone Loss, Osteoporosis

Intervention / Treatment
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* Drug: Zoledronic acid
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: In-patient at Rehabilitation Institute of Chicago (RIC) or an outpatient who was recently discharged from RIC Males and females Age >/=18 years Medically stable in the opinion of subject's physiatrist SCI at within 120 days inclusive at time of screening SCI with inability to ambulate independently ASIA Impairment Scale (AIS) A, B, or C, at time of study entry Capable of positioning to have DXA performed Able to tolerate acetaminophen No known endocrinopathies (diabetes type 1 or 2 can be included) Normal TSH levels Normal 25-OH vitamin D levels (>/= 20 ng/ml) at baseline (subjects may be repleted) Normal calcium levels Normal renal function (creatinine <2.0 mg/dl) Well hydrated with adequate intake of liquids Able to return for all follow-up visits Capable of reading and understanding informed consent document Males and females of childbearing potential must be willing and able to use double barrier method of contraception for 2 months after having received study drug Exclusion Criteria: Have Paget's disease of the bone Malignancy as a cause of acute SCI Have unexplained high levels of alkaline phosphatase in blood Any active gastrointestinal condition that results in malabsorption Poor dental hygiene or requirement for invasive dental procedure within two months prior to enrollment History of bone metastasis and skeletal malignancies History of alcoholism or drug abuse within the 2 years prior to study screening Other medical conditions that in the opinion of the investigator would preclude the subject from completing the study Elevated liver function tests >2x normal Currently being prescribed anti-convulsants at a dose or frequency that is determined to interfere with bone metabolism as determined by the investigator Currently being prescribed glucocorticoids, other than inhaled glucocorticoids Current or recent use any bone-active agents, including any bisphosphonate, raloxifene, hormone therapy (estrogen and estrogen/progestin), calcitonin or strontium-containing compounds within 60 days of screening. Pregnant, planning to become pregnant, or lactating

Ages Eligible for Study
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Minimum Age: 18 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
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Zol<br>Intravenous infusion of zoledronic acid (zol) 5 mg at baseline. | Drug: Zoledronic acid<br>* Intravenous infusion of zoledronic acid 5 mg.<br>* Other names: Bisphosphonate;|
| Experimental: Placebo<br>Intravenous infusion of placebo at baseline. | Drug: Placebo<br>* Placebo (saline) infusion to match zoledronic acid<br>* Other names: Saline;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change in Bone Mass Density (BMD) in the Hip | Percent change of bone mass density (BMD) in the total hip (as measured by DXA) | 0-12 months | 
| Percent Change of Bone Mass Density (BMD) in the Femoral Neck | Percent change of bone mass density (BMD) in the femoral neck (as measured by DXA) | 0-12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change in the Epiphyseal Integral Bone Mass Content (iBMC) of the Femur | Percent change in the epiphyseal integral bone mass content (iBMC) of the femur, as collected by CT. | 0-12 months | 
| Percent Change in the Metaphyseal Integral Bone Mass Content (iBMC) of the Femur | Percent change in the metaphyseal integral bone mass content (iBMC) of the femur, as collected by CT | 0-12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Osteoporosis, Spinal Cord Injury, Bone Diseases, Metabolic Bone Diseases, Musculoskeletal Diseases, Spinal Cord Diseases, Central Nervous System Diseases, Nervous System Diseases, Nervous System, Wounds and Injuries, Bone Density Conservation Agents, Physiological Effects of Drugs, Pharmacologic Actions, Department of Defense