Zoledronic Acid in Acute Spinal Cord Injury

NCT01642901 | Completed Phase 3 Results DMC

• 1 other identifier: 11F.612
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

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.

Conditions

Spinal Cord Injury

Keywords

spinal cord injury; bone mineral density

Outcome Measures

Primary Outcomes (4)

• Change in Areal Bone Mineral Density at Hip

  Percent change in areal bone mineral density (aBMD) assessed by dual energy X-ray absorptiometry (DXA) at 4 months compared to baseline. This will compare aBMD at the hip.

  4 months

• Change in Areal Bone Mineral Density at Knee

  Percent change in areal bone mineral density (aBMD) assessed by dual energy X-ray absorptiometry (DXA) at 4 months compared to baseline. This will compare aBMD at the distal femur and proximal tibia.

  4 months

• Change in Areal Bone Mineral Density at Hip

  Percent change in areal bone mineral density (aBMD) assessed by dual energy X-ray absorptiometry (DXA) at 12 months post-injury compared to baseline. This will compare aBMD at the hip.

  one year

• Change in Areal Bone Mineral Density at Knee

  Percent change in areal bone mineral density (aBMD) assessed by dual energy X-ray absorptiometry (DXA) at 12 months post-injury compared to baseline. This will compare aBMD at the distal femur and proximal tibia.

  one year

Secondary Outcomes (3)

• Change in Biomarkers of Bone Resorption (sCTX)

  1 month, 4 months, 12 months

• Change in Biomarkers of Bone Formation (P1NP)

  1 month, 4 months

• Safety and Tolerability of Zoledronic Acid

  72-hours and 1 month post intervention.

Study Arms (2)

Zoledronic Acid 5 mg IV infusion

EXPERIMENTAL

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

Drug: Zoledronic acid

normal saline 0.9%

PLACEBO COMPARATOR

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.

Drug: normal saline 0.9%

Interventions

Zoledronic acid 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.

Also known as: Reclast

Zoledronic Acid 5 mg IV infusion

normal saline 0.9% 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

Also known as: normal saline, 0.9% saline

normal saline 0.9%

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Thomas Jefferson University: lead
• Department of Health and Human Services: collaborator

Study Sites (1)

Thomas Jefferson University and Hospital

Philadelphia, Pennsylvania, 19107, United States

Location

Related Publications (1)

• 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.

  PMID: 32055041 BACKGROUND

MeSH Terms

Conditions

Spinal Cord Injuries

Interventions

Zoledronic Acid; Saline Solution

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Diphosphonates; Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Limitations and Caveats

Enrollment was significantly less than projected due to competing acute clinical trials, reducing the power of the study to identify significant differences. DXA imaging, particularly at the knee was limited by positioning on the table in some individuals with evolving contractures in either knee flexion or hip rotation.

Results Point of Contact

• Title: Christina V Oleson, MD
• Organization: MetroHealth Rehabilitation Institute

coleson@metrohealth.org

216-778-4414

Study Officials

• Christina V Oleson, MD

  Thomas Jefferson University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 6, 2012
• First Posted: July 17, 2012
• Study Start: September 1, 2012
• Primary Completion: March 1, 2018
• Study Completion: March 1, 2018
• Last Updated: May 23, 2023
• Results First Posted: May 23, 2023

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)