Zoledronic Acid in Acute Spinal Cord Injury

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2014 by Thomas Jefferson University
Sponsor:
Collaborator:
U.S. Department of Education
Information provided by (Responsible Party):
Thomas Jefferson University
ClinicalTrials.gov Identifier:
NCT01642901
First received: July 6, 2012
Last updated: February 4, 2014
Last verified: February 2014
  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:


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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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: February 4, 2014
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
Wounds and Injuries
Spinal Cord Diseases
Central Nervous System Diseases
Nervous System Diseases
Trauma, Nervous System
Zoledronic acid
Diphosphonates
Bone Density Conservation Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 24, 2014