Zoledronic Acid in Acute Spinal Cord Injury

• Status: Unknown status
• Trial end date: 2021-03-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Thomas Jefferson University
• Collaborators: Department of Health and Human Services; U.S. Department of Education
• Treatments: Diphosphonates; Zoledronic Acid

Criteria

Inclusion Criteria:

• Ages 18-65, male or female

• Traumatic SCI with Neurological level C4-T10, AIS (ASIA Impairment Scale) A,

• Serum calcium level >7.0 mg/dL) at time of study drug administration

• Screening baseline serum 25OH (25-hydroxy) 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 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