Clinical trial NCT01642901: Zoledronic Acid in Acute Spinal Cord Injury
Official title: Zoledronic Acid to Prevent Bone Loss After Acute Spinal Cord Injury
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Spinal Cord Injury
Keywords: spinal cord injury
bone mineral density
Lead sponsor: Thomas Jefferson University
Sponsor class: OTHER
Collaborators: name: Department of Health and Human Services
First posted: 2012-07-17
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

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

Primary outcomes:
measure: Change in Areal Bone Mineral Density at Hip
timeFrame: 4 months
measure: Change in Areal Bone Mineral Density at Knee
timeFrame: 4 months
measure: Change in Areal Bone Mineral Density at Hip
timeFrame: one year
measure: Change in Areal Bone Mineral Density at Knee
timeFrame: one year
Secondary outcomes:
measure: Change in Biomarkers of Bone Resorption (sCTX)
timeFrame: 1 month, 4 months, 12 months
measure: Change in Biomarkers of Bone Formation (P1NP)
timeFrame: 1 month, 4 months
measure: Safety and Tolerability of Zoledronic Acid
timeFrame: 72-hours and 1 month post intervention.
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: Thomas Jefferson University and Hospital
state: Pennsylvania
Study officials:
affiliation: Thomas Jefferson University
name: Christina V Oleson, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Oleson CV, Marino RJ, Formal CS, Modlesky CM, Leiby BE. The effect of zoledronic acid on attenuation of bone loss at the hip and knee following acute traumatic spinal cord injury: a randomized-controlled study. Spinal Cord. 2020 Aug;58(8):921-929. doi: 10.1038/s41393-020-0431-9. Epub 2020 Feb 13.