Zoledronic Acid in Acute Spinal Cord Injury - Full Text View

Purpose

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 14 days of an SCI.

Condition	Intervention	Phase
Complete Traumatic Spinal Cord Injury	Drug: Zoledronic acid Drug: normal saline 0.9%	Phase 3

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	Zoledronic Acid to Prevent Bone Loss After Acute Spinal Cord Injury

Resource links provided by NLM:

MedlinePlus related topics: Bone Density Minerals Spinal Cord Injuries

Drug Information available for: Zoledronic acid

U.S. FDA Resources

Further study details as provided by Thomas Jefferson University:

Primary Outcome Measures:

change in bone mineral density [ Time Frame: one year ] [ Designated as safety issue: No ]
Change in bone mineral density (BMD) assessed by dual energy X-ray absorptiometry (DXA) at baseline, 4 months, and 12 months post-injury.

This will compare BMD at the hip, distal femur and proximal tibia.

Secondary Outcome Measures:

Biomarkers of bone formation and resorption [ Time Frame: Baseline, 1 month, 4 month, and 12 months ] [ Designated as safety issue: No ]
Collection of blood biomarkers of bone formation and resorption at selected time intervals within the first 12 months post-injury.

This will observe the timing of metabolic indexes of bone formation and resorption, and of pro-osteoclastogenic factors promoting bone resorption.
safety and tolerability of zoledronic acid [ Time Frame: one year ] [ Designated as safety issue: Yes ]
Assessment of the safety and tolerability of zoledronic acid in the acute spinal cord injury population. This will be done by examination reportable adverse events including fevers, flu-like symptoms, GI upset as measures of safety and report of patient's willingness to have participate in physical therapy in the first week after receiving medication as a measure of tolerability

Estimated Enrollment:	48
Study Start Date:	May 2012
Estimated Study Completion Date:	May 2017
Estimated Primary Completion Date:	January 2017 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: zoledronic acid 5 mg IV infusion Single infusion of 5 mg intravenous zoledronic acid given within 14 days of acute traumatic spinal cord injury	Drug: Zoledronic acid 5 mg zoledronic acid infused intravenously over two hours (2.5mg per hour), given only once, within 14 days of acute traumatic spinal cord injury. Other Name: Reclast
Placebo Comparator: saline placebo Infusion of normal saline of equivalent volume to reconstituted zoledronic acid, given only once and run over 2 hours, to occur within 14 days of acute traumatic spinal cord injury	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 14 days of acute traumatic spinal cord injury Other Names: normal saline 0.9% saline

Eligibility

Ages Eligible for Study:	18 Years to 65 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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
Hypotension requiring use of intravenous blood pressure agents such as dopamine, norepinephrine or phenylephrine
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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01642901

Contacts

Contact: Christina V Oleson, MD	215-955-6579	christina.oleson@jefferson.edu
Contact: Ralph J Marino, MD	215-955-6579	ralph.marino@jefferson.edu

Locations

United States, Pennsylvania
Thomas Jefferson University and Hospital	Recruiting
Philadelphia, Pennsylvania, United States, 19107
Contact: Marilyn J Owens, RN 215-955-6579 marilyn.owens@jefferson.edu
Principal Investigator: Christina V Oleson, MD
Sub-Investigator: Ralph J Marino, MD

Sponsors and Collaborators

Thomas Jefferson University

U.S. Department of Education

Investigators

Principal Investigator:

Christina V Oleson, MD

Thomas Jefferson University

More Information

No publications provided

Responsible Party:	Thomas Jefferson University
ClinicalTrials.gov Identifier:	NCT01642901 History of Changes
Other Study ID Numbers:	11F.612
Study First Received:	July 6, 2012
Last Updated:	May 20, 2013
Health Authority:	United States: Federal Government

Keywords provided by Thomas Jefferson University:

spinal cord injury
bone mineral density

Additional relevant MeSH terms:

Spinal Cord Injuries
Spinal Cord Diseases
Central Nervous System Diseases
Nervous System Diseases
Trauma, Nervous System
Wounds and Injuries

Zoledronic acid
Diphosphonates
Bone Density Conservation Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on May 22, 2013