Zoledronic Acid in Acute Spinal Cord Injury

• ClinicalTrials.gov Identifier: NCT01642901
• Recruitment Status: Active, not recruiting
• First Posted: July 17, 2012
• Last Update Posted: September 13, 2018
• Sponsor: Thomas Jefferson University
• Collaborator: Department of Health and Human Services
• Information provided by (Responsible Party): Thomas Jefferson University

Tracking Information

• First Submitted Date: July 6, 2012
• First Posted Date: July 17, 2012
• Last Update Posted Date: September 13, 2018
• Study Start Date: May 2012
• Actual Primary Completion Date: March 2018 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 12, 2012)

change in bone mineral density [ Time Frame: one year ]

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.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: July 12, 2012)

• Biomarkers of bone formation and resorption [ Time Frame: Baseline, 1 month, 4 month, and 12 months ]
  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 ]
  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

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Zoledronic Acid in Acute Spinal Cord Injury
• Official Title: Zoledronic Acid to Prevent Bone Loss After Acute Spinal Cord Injury
• 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.
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Spinal Cord Injury

Intervention

• Drug: 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.
  Other Name: Reclast
• 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
  Other Names:

  • normal saline
  • 0.9% saline

Study Arms

• Experimental: Zoledronic Acid 5 mg IV infusion
  Single infusion of 5 mg intravenous zoledronic acid given within 21 days of acute traumatic spinal cord injury.
  Intervention: Drug: Zoledronic acid
• Placebo Comparator: 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.
  Intervention: Drug: normal saline 0.9%

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: November 8, 2017): 15
• Original Estimated Enrollment (submitted: July 12, 2012): 48
• Estimated Study Completion Date: March 2021
• Actual Primary Completion Date: March 2018 (Final data collection date for primary outcome measure)

Eligibility 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 65 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT01642901
• Other Study ID Numbers: 11F.612
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: Yes

• Responsible Party: Thomas Jefferson University
• Study Sponsor: Thomas Jefferson University
• Collaborators: Department of Health and Human Services

Investigators

• Principal Investigator: Christina V Oleson, MD; Thomas Jefferson University

• PRS Account: Thomas Jefferson University
• Verification Date: September 2018