Zoledronic Acid in Acute Spinal Cord Injury

Thomas Jefferson University

Status and phase: Completed; Phase 3

Conditions: Spinal Cord Injury

Treatments: Drug: normal saline 0.9%; Drug: Zoledronic acid

Study type: Interventional

Funder types: Other; Other U.S. Federal agency

Identifiers

NCT01642901

11F.612

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 16 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 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

Exclusion criteria

• 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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16 participants in 2 patient groups, including a placebo group

Zoledronic Acid 5 mg IV infusion

Experimental group

Description:

Single infusion of 5 mg intravenous zoledronic acid given within 21 days of acute traumatic spinal cord injury.

Treatment:

Drug: Zoledronic acid

normal saline 0.9%

Placebo Comparator group

Description:

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.

Treatment:

Drug: normal saline 0.9%