Zoledronic Acid in Acute Spinal Cord Injury
Condition: Spinal Cord Injury
MeSH terms: Spinal Cord Injuries; Wounds and Injuries
Intervention: Zoledronic acid; normal saline 0.9%
Intervention description: 5 mg zoledronic acid infused intravenously over two hours (2.5mg per hour), given only once, within 21 days of acute traumatic spinal cord injury.; Infusion of equivalent volume of 0.9% normal saline to that of the reconstituted zoledronic acid, given only once over two hours, occurring within 21 days of acute traumatic spinal cord injury
Intervention MeSH terms: Zoledronic Acid
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 16.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: spinal cord injury; bone mineral density

Summary:

      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.
    

Eligibility criteria:

        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