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Zoledronic Acid in Acute Spinal Cord Injury

Primary Purpose

Spinal Cord Injury

Status
Completed
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Zoledronic acid
normal saline 0.9%
Sponsored by
Thomas Jefferson University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Spinal Cord Injury focused on measuring spinal cord injury, bone mineral density

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Thomas Jefferson University and Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Zoledronic Acid 5 mg IV infusion

normal saline 0.9%

Arm Description

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

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.

Outcomes

Primary Outcome Measures

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.
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.
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.
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.

Secondary Outcome Measures

Change in Biomarkers of Bone Resorption (sCTX)
Change in sCTX from baseline to 1- and 4-months post intervention and 12-months post-injury.
Change in Biomarkers of Bone Formation (P1NP)
Change in serum P1NP from baseline to 1- and 4-months post intervention.
Safety and Tolerability of Zoledronic Acid
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

Full Information

First Posted
July 6, 2012
Last Updated
May 1, 2023
Sponsor
Thomas Jefferson University
Collaborators
Department of Health and Human Services
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1. Study Identification

Unique Protocol Identification Number
NCT01642901
Brief Title
Zoledronic Acid in Acute Spinal Cord Injury
Official Title
Zoledronic Acid to Prevent Bone Loss After Acute Spinal Cord Injury
Study Type
Interventional

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Completed
Study Start Date
September 2012 (Actual)
Primary Completion Date
March 2018 (Actual)
Study Completion Date
March 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Thomas Jefferson University
Collaborators
Department of Health and Human Services

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Spinal Cord Injury
Keywords
spinal cord injury, bone mineral density

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
16 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Zoledronic Acid 5 mg IV infusion
Arm Type
Experimental
Arm Description
Single infusion of 5 mg intravenous zoledronic acid given within 21 days of acute traumatic spinal cord injury.
Arm Title
normal saline 0.9%
Arm Type
Placebo Comparator
Arm Description
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 Type
Drug
Intervention Name(s)
Zoledronic acid
Other Intervention Name(s)
Reclast
Intervention Description
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
Intervention Name(s)
normal saline 0.9%
Other Intervention Name(s)
normal saline, 0.9% saline
Intervention Description
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
Primary Outcome Measure Information:
Title
Change in Areal Bone Mineral Density at Hip
Description
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.
Time Frame
4 months
Title
Change in Areal Bone Mineral Density at Knee
Description
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.
Time Frame
4 months
Title
Change in Areal Bone Mineral Density at Hip
Description
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.
Time Frame
one year
Title
Change in Areal Bone Mineral Density at Knee
Description
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.
Time Frame
one year
Secondary Outcome Measure Information:
Title
Change in Biomarkers of Bone Resorption (sCTX)
Description
Change in sCTX from baseline to 1- and 4-months post intervention and 12-months post-injury.
Time Frame
1 month, 4 months, 12 months
Title
Change in Biomarkers of Bone Formation (P1NP)
Description
Change in serum P1NP from baseline to 1- and 4-months post intervention.
Time Frame
1 month, 4 months
Title
Safety and Tolerability of Zoledronic Acid
Description
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
Time Frame
72-hours and 1 month post intervention.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
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 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Christina V Oleson, MD
Organizational Affiliation
Thomas Jefferson University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Thomas Jefferson University and Hospital
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19107
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
32055041
Citation
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.
Results Reference
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Zoledronic Acid in Acute Spinal Cord Injury

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