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Prevention of Bone Loss After Acute SCI by Zoledronic Acid

Primary Purpose

Spinal Cord Injury, Acute Spinal Cord Injury, Bone Loss

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Zoledronic acid
Placebo
Sponsored by
Northwestern University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Spinal Cord Injury focused on measuring Osteoporosis, Spinal Cord Injury, Bone Diseases, Metabolic Bone Diseases, Musculoskeletal Diseases, Spinal Cord Diseases, Central Nervous System Diseases, Nervous System Diseases, Nervous System, Wounds and Injuries, Bone Density Conservation Agents, Physiological Effects of Drugs, Pharmacologic Actions, Department of Defense

Eligibility Criteria

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

Inclusion Criteria:

  • In-patient at Rehabilitation Institute of Chicago (RIC) or an outpatient who was recently discharged from RIC
  • Males and females
  • Age >/=18 years
  • Medically stable in the opinion of subject's physiatrist
  • SCI at within 120 days inclusive at time of screening
  • SCI with inability to ambulate independently
  • ASIA Impairment Scale (AIS) A, B, or C, at time of study entry
  • Capable of positioning to have DXA performed
  • Able to tolerate acetaminophen
  • No known endocrinopathies (diabetes type 1 or 2 can be included)
  • Normal TSH levels
  • Normal 25-OH vitamin D levels (>/= 20 ng/ml) at baseline (subjects may be repleted)
  • Normal calcium levels
  • Normal renal function (creatinine <2.0 mg/dl)
  • Well hydrated with adequate intake of liquids
  • Able to return for all follow-up visits
  • Capable of reading and understanding informed consent document
  • Males and females of childbearing potential must be willing and able to use double barrier method of contraception for 2 months after having received study drug

Exclusion Criteria:

  • Have Paget's disease of the bone
  • Malignancy as a cause of acute SCI
  • Have unexplained high levels of alkaline phosphatase in blood
  • Any active gastrointestinal condition that results in malabsorption
  • Poor dental hygiene or requirement for invasive dental procedure within two months prior to enrollment
  • History of bone metastasis and skeletal malignancies
  • History of alcoholism or drug abuse within the 2 years prior to study screening
  • Other medical conditions that in the opinion of the investigator would preclude the subject from completing the study
  • Elevated liver function tests >2x normal
  • Currently being prescribed anti-convulsants at a dose or frequency that is determined to interfere with bone metabolism as determined by the investigator
  • Currently being prescribed glucocorticoids, other than inhaled glucocorticoids
  • Current or recent use any bone-active agents, including any bisphosphonate, raloxifene, hormone therapy (estrogen and estrogen/progestin), calcitonin or strontium-containing compounds within 60 days of screening.
  • Pregnant, planning to become pregnant, or lactating

Sites / Locations

  • Northwestern University Feinberg School of Medicine
  • Rehabilitation Institute of Chicago

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Zol

Placebo

Arm Description

Intravenous infusion of zoledronic acid (zol) 5 mg at baseline.

Intravenous infusion of placebo at baseline.

Outcomes

Primary Outcome Measures

Percent Change in Bone Mass Density (BMD) in the Hip
Percent change of bone mass density (BMD) in the total hip (as measured by DXA)
Percent Change of Bone Mass Density (BMD) in the Femoral Neck
Percent change of bone mass density (BMD) in the femoral neck (as measured by DXA)

Secondary Outcome Measures

Percent Change in the Epiphyseal Integral Bone Mass Content (iBMC) of the Femur
Percent change in the epiphyseal integral bone mass content (iBMC) of the femur, as collected by CT.
Percent Change in the Metaphyseal Integral Bone Mass Content (iBMC) of the Femur
Percent change in the metaphyseal integral bone mass content (iBMC) of the femur, as collected by CT

Full Information

First Posted
December 21, 2014
Last Updated
June 8, 2021
Sponsor
Northwestern University
Collaborators
United States Department of Defense
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1. Study Identification

Unique Protocol Identification Number
NCT02325414
Brief Title
Prevention of Bone Loss After Acute SCI by Zoledronic Acid
Official Title
Prevention of Bone Loss After Acute SCI by Zoledronic Acid: Durability, Effect on Bone Strength, and Use of Biomarkers to Guide Therapy
Study Type
Interventional

2. Study Status

Record Verification Date
June 2021
Overall Recruitment Status
Completed
Study Start Date
February 2015 (Actual)
Primary Completion Date
August 25, 2020 (Actual)
Study Completion Date
August 25, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Northwestern University
Collaborators
United States Department of Defense

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The overall objective of this study is to define an effective therapeutic approach, using currently available medication, to prevent or mitigate the loss of bone mass and bone strength that occurs after acute spinal cord injury.
Detailed Description
This is a randomized, double-blind placebo-controlled study of zoledronic acid to evaluate its efficacy and safety over a 2 year period for the prevention of bone loss and maintenance of bone strength in individuals with recent onset SCI (see diagram below). Subjects will be randomized at the baseline visit to receive either zoledronic acid or placebo. At the end of the first year of the study, each treatment group will be re-randomized to either zoledronic acid or placebo to evaluate the durability of response to zoledronic acid and the utility of serum bone markers to guide therapeutic decision making. DXA imaging, CT imaging and bone markers will be obtained at baseline, 3 months, 6 months, 12 months, 18 months and 24 months.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Spinal Cord Injury, Acute Spinal Cord Injury, Bone Loss, Osteoporosis
Keywords
Osteoporosis, Spinal Cord Injury, Bone Diseases, Metabolic Bone Diseases, Musculoskeletal Diseases, Spinal Cord Diseases, Central Nervous System Diseases, Nervous System Diseases, Nervous System, Wounds and Injuries, Bone Density Conservation Agents, Physiological Effects of Drugs, Pharmacologic Actions, Department of Defense

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
60 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Zol
Arm Type
Experimental
Arm Description
Intravenous infusion of zoledronic acid (zol) 5 mg at baseline.
Arm Title
Placebo
Arm Type
Experimental
Arm Description
Intravenous infusion of placebo at baseline.
Intervention Type
Drug
Intervention Name(s)
Zoledronic acid
Other Intervention Name(s)
Reclast, Zometa, Bisphosphonate
Intervention Description
Intravenous infusion of zoledronic acid 5 mg.
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
Saline
Intervention Description
Placebo (saline) infusion to match zoledronic acid
Primary Outcome Measure Information:
Title
Percent Change in Bone Mass Density (BMD) in the Hip
Description
Percent change of bone mass density (BMD) in the total hip (as measured by DXA)
Time Frame
0-12 months
Title
Percent Change of Bone Mass Density (BMD) in the Femoral Neck
Description
Percent change of bone mass density (BMD) in the femoral neck (as measured by DXA)
Time Frame
0-12 months
Secondary Outcome Measure Information:
Title
Percent Change in the Epiphyseal Integral Bone Mass Content (iBMC) of the Femur
Description
Percent change in the epiphyseal integral bone mass content (iBMC) of the femur, as collected by CT.
Time Frame
0-12 months
Title
Percent Change in the Metaphyseal Integral Bone Mass Content (iBMC) of the Femur
Description
Percent change in the metaphyseal integral bone mass content (iBMC) of the femur, as collected by CT
Time Frame
0-12 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: In-patient at Rehabilitation Institute of Chicago (RIC) or an outpatient who was recently discharged from RIC Males and females Age >/=18 years Medically stable in the opinion of subject's physiatrist SCI at within 120 days inclusive at time of screening SCI with inability to ambulate independently ASIA Impairment Scale (AIS) A, B, or C, at time of study entry Capable of positioning to have DXA performed Able to tolerate acetaminophen No known endocrinopathies (diabetes type 1 or 2 can be included) Normal TSH levels Normal 25-OH vitamin D levels (>/= 20 ng/ml) at baseline (subjects may be repleted) Normal calcium levels Normal renal function (creatinine <2.0 mg/dl) Well hydrated with adequate intake of liquids Able to return for all follow-up visits Capable of reading and understanding informed consent document Males and females of childbearing potential must be willing and able to use double barrier method of contraception for 2 months after having received study drug Exclusion Criteria: Have Paget's disease of the bone Malignancy as a cause of acute SCI Have unexplained high levels of alkaline phosphatase in blood Any active gastrointestinal condition that results in malabsorption Poor dental hygiene or requirement for invasive dental procedure within two months prior to enrollment History of bone metastasis and skeletal malignancies History of alcoholism or drug abuse within the 2 years prior to study screening Other medical conditions that in the opinion of the investigator would preclude the subject from completing the study Elevated liver function tests >2x normal Currently being prescribed anti-convulsants at a dose or frequency that is determined to interfere with bone metabolism as determined by the investigator Currently being prescribed glucocorticoids, other than inhaled glucocorticoids Current or recent use any bone-active agents, including any bisphosphonate, raloxifene, hormone therapy (estrogen and estrogen/progestin), calcitonin or strontium-containing compounds within 60 days of screening. Pregnant, planning to become pregnant, or lactating
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Thomas J Schnitzer, MD, PhD
Organizational Affiliation
Northwestern University Feinberg School of Medicine
Official's Role
Principal Investigator
Facility Information:
Facility Name
Northwestern University Feinberg School of Medicine
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
Rehabilitation Institute of Chicago
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
34278611
Citation
Edwards WB, Haider IT, Simonian N, Barroso J, Schnitzer TJ. Durability and delayed treatment effects of zoledronic acid on bone loss after spinal cord injury: a randomized, controlled trial. J Bone Miner Res. 2021 Nov;36(11):2127-2138. doi: 10.1002/jbmr.4416. Epub 2021 Jul 29. Erratum In: J Bone Miner Res. 2023 Jul;38(7):1043.
Results Reference
derived
PubMed Identifier
30334093
Citation
Haider IT, Lobos SM, Simonian N, Schnitzer TJ, Edwards WB. Bone fragility after spinal cord injury: reductions in stiffness and bone mineral at the distal femur and proximal tibia as a function of time. Osteoporos Int. 2018 Dec;29(12):2703-2715. doi: 10.1007/s00198-018-4733-0. Epub 2018 Oct 17.
Results Reference
derived

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Prevention of Bone Loss After Acute SCI by Zoledronic Acid

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