Zoledronic Acid in Acute Spinal Cord Injury

NCT ID: NCT01642901

Last Updated: 2023-05-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 16 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-09-30
• Study Completion Date: 2018-03-31

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.

Conditions

Spinal Cord Injury

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Zoledronic Acid 5 mg IV infusion

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

Group Type: EXPERIMENTAL

Zoledronic acid

Intervention Type: DRUG

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.

normal saline 0.9%

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.

Group Type: PLACEBO_COMPARATOR

normal saline 0.9%

Intervention Type: DRUG

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

Interventions

Zoledronic acid

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.

Intervention Type: DRUG

normal saline 0.9%

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 Type: DRUG

Other Intervention Names

Reclast; normal saline; 0.9% saline

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
• 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Department of Health and Human Services

FED

Sponsor Role: collaborator

Thomas Jefferson University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Christina V Oleson, MD

Role: PRINCIPAL_INVESTIGATOR

Thomas Jefferson University

Locations

Thomas Jefferson University and Hospital

Philadelphia, Pennsylvania, United States

Countries

United States

References

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.

Reference Type: BACKGROUND

PMID: 32055041 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

11F.612

Identifier Type: -

Identifier Source: org_study_id