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Denosumab Administration After Spinal Cord Injury

Primary Purpose

Osteoporosis, Spinal Cord Injury

Status
Unknown status
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Denosumab
Placebo (identical Denosumab volume of normal saline)
Sponsored by
James J. Peters Veterans Affairs Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Osteoporosis focused on measuring Spinal Cord Injury, Denosumab, Osteoporosis, Dual Energy X-ray Absorptiometry

Eligibility Criteria

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

Inclusion Criteria:

  1. Complete motor SCI [American Spinal Injury Association Impairment Scale (AIS) grade A and B];
  2. Duration of injury <12 weeks; and
  3. Males between the ages of 18 and 65 years old and females between the ages of 18 and 50 years old.

Exclusion Criteria:

  1. Extensive life-threatening injuries in addition to SCI;
  2. Acute fracture or extensive bone trauma;
  3. History of prior bone disease (Paget's hyperparathyroidism, osteoporosis, etc.)
  4. Post menopausal women;
  5. Men with known hypogonadism prior to SCI;
  6. Anabolic or Steroid hormonal therapy; within the past year and longer than six months;
  7. Hyperthyroidism;
  8. Cushing's disease or syndrome;
  9. Severe underlying chronic disease;
  10. Heterotopic ossification of the knee region (HO limited to the hip region only will not exclude subject participation);
  11. History of chronic alcohol abuse;
  12. Diagnosis of Hypocalcemia;
  13. Pregnancy;
  14. Existing dental condition/dental infection
  15. Any patient taking a bisphosphonate for heterotopic ossification (HO);
  16. Current diagnosis of cancer or history of cancer; and
  17. Any patient receiving moderate or high dose corticosteroids (>40 mg/d prednisone or an equivalent dose of other corticosteroid) for longer than one week, not including drug administered in an attempt to preserve neurological function at the time of acute SCI.

Sites / Locations

  • Kessler Institute for RehabilitationRecruiting
  • James J. Peters VA Medical CenterRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Experimental

Arm Label

Placebo

Denosumab

Arm Description

A group of participants will be randomized to the placebo group and will receive the identical volume of normal saline at parallel time points.

A group of participants will be randomized to the experimental group and will have Denosumab (Prolia, 60 mg SC) administered at baseline, 6 and 12 months.

Outcomes

Primary Outcome Measures

Bone mineral density (BMD) of the distal femur
Change in BMD at the distal femur will be obtained by dual energy X-ray absorptiometry (DXA) at baseline, 1, 3, 6, 12, and 18 months after Denosumab administration.

Secondary Outcome Measures

Bone microarchitecture of the distal femur and proximal tibia.
Change in microarchitecture at the distal femur and proximal tibia will be obtained by peripheral quantitative computerized tomography (pQCT) at baseline, 12, and 18 months after Denosumab administration.

Full Information

First Posted
November 6, 2013
Last Updated
March 6, 2019
Sponsor
James J. Peters Veterans Affairs Medical Center
Collaborators
Kessler Institute for Rehabilitation
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1. Study Identification

Unique Protocol Identification Number
NCT01983475
Brief Title
Denosumab Administration After Spinal Cord Injury
Official Title
The Efficacy of Denosumab to Reduce Osteoporosis After Spinal Cord Injury
Study Type
Interventional

2. Study Status

Record Verification Date
March 2019
Overall Recruitment Status
Unknown status
Study Start Date
January 2015 (undefined)
Primary Completion Date
May 2020 (Anticipated)
Study Completion Date
May 2020 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
James J. Peters Veterans Affairs Medical Center
Collaborators
Kessler Institute for Rehabilitation

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Sublesional bone loss after acute spinal cord injury (SCI) is sudden, progressive, and dramatic. After depletion of bone mass and the loss of architectural integrity, it may be difficult, if even possible, to restore skeletal mass and strength. Denosumab is a relative new, highly potent anti-resorptive agent that has proven efficacy in postmenopausal osteoporosis to improve bone mass and in solid tumor patients to prevent a skeletal-related event to a greater extent than that with bisphosphonate administration. In persons with complete motor lesions, bisphosphonates have not been effective at reducing bone loss at the knee, the site of greatest relevance because of its increased risk of fracture. Anti-RANKL therapy appears to be more potent than bisphosphonates in animal models of bone loss due to immobilization, suggesting that treatment with denosumab may prove to be an efficacious therapy for persons with acute SCI to preserve bone mass and strength.
Detailed Description
The primary objective of this study is to test the efficacy of a potent anti-resorptive agent, denosumab [receptor activator of nuclear factor-κB ligand (RANKL) antibody; Amgen Inc.] to preserve bone mass at the hip and knee and trabecular connectivity at the knee after acute SCI. Setting: patient enrollment, study drug administration and DXA scanning will be completed at the Kessler Institute for Rehabilitation (KIR) and pQCT measurements will be performed at Columbia University. A Randomized, double-blind, placebo-controlled parallel group trial. Twenty-four subjects with acute, motor complete SCI (≤12 weeks) who have been admitted to the Kessler Institute for Rehabilitation (KIR) will be recruited for participation. The age of study participation will be males between the ages of 18 and 65 years old and females between the ages of 18 and 50 years old. Primary outcome measure will be BMD as measured by DXA and microarchitecture as measured by pQCT at the hip and knee.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Osteoporosis, Spinal Cord Injury
Keywords
Spinal Cord Injury, Denosumab, Osteoporosis, Dual Energy X-ray Absorptiometry

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
24 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
A group of participants will be randomized to the placebo group and will receive the identical volume of normal saline at parallel time points.
Arm Title
Denosumab
Arm Type
Experimental
Arm Description
A group of participants will be randomized to the experimental group and will have Denosumab (Prolia, 60 mg SC) administered at baseline, 6 and 12 months.
Intervention Type
Drug
Intervention Name(s)
Denosumab
Other Intervention Name(s)
Prolia
Intervention Description
In clinical trials, denosumab (Amgen Inc., Thousand Oaks, CA), has been shown to be more potent in reducing osteoclastosis and function than bisphosphonates.39,40 The rate of bone loss in the lower extremity at sites of interest in patients with acute SCI has been reported to be several-fold greater than the rate of bone loss in postmenopausal women not prescribed antiresorptive medications, which is about 3-5% per year.11,50,51 The dose of denosumab chosen for our protocol in patients after acute SCI will be the same dose that has been shown to be efficacious to treat postmenopausal osteoporosis (60 mg SQ q 6 months).
Intervention Type
Drug
Intervention Name(s)
Placebo (identical Denosumab volume of normal saline)
Other Intervention Name(s)
Unknown at this time
Intervention Description
The placebo group will receive the identical volume of normal saline at parallel time points.
Primary Outcome Measure Information:
Title
Bone mineral density (BMD) of the distal femur
Description
Change in BMD at the distal femur will be obtained by dual energy X-ray absorptiometry (DXA) at baseline, 1, 3, 6, 12, and 18 months after Denosumab administration.
Time Frame
Baseline, 1, 3, 6, 12, and 18 months after Denosumab administration
Secondary Outcome Measure Information:
Title
Bone microarchitecture of the distal femur and proximal tibia.
Description
Change in microarchitecture at the distal femur and proximal tibia will be obtained by peripheral quantitative computerized tomography (pQCT) at baseline, 12, and 18 months after Denosumab administration.
Time Frame
Baseline, 12, and 18 months after Denosumab administration

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: Complete motor SCI [American Spinal Injury Association Impairment Scale (AIS) grade A and B]; Duration of injury <12 weeks; and Males between the ages of 18 and 65 years old and females between the ages of 18 and 50 years old. Exclusion Criteria: Extensive life-threatening injuries in addition to SCI; Acute fracture or extensive bone trauma; History of prior bone disease (Paget's hyperparathyroidism, osteoporosis, etc.) Post menopausal women; Men with known hypogonadism prior to SCI; Anabolic or Steroid hormonal therapy; within the past year and longer than six months; Hyperthyroidism; Cushing's disease or syndrome; Severe underlying chronic disease; Heterotopic ossification of the knee region (HO limited to the hip region only will not exclude subject participation); History of chronic alcohol abuse; Diagnosis of Hypocalcemia; Pregnancy; Existing dental condition/dental infection Any patient taking a bisphosphonate for heterotopic ossification (HO); Current diagnosis of cancer or history of cancer; and Any patient receiving moderate or high dose corticosteroids (>40 mg/d prednisone or an equivalent dose of other corticosteroid) for longer than one week, not including drug administered in an attempt to preserve neurological function at the time of acute SCI.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Christopher M Cirnigliaro, M.S.
Phone
973-731-3900
Ext
2755
Email
christopher.cirnigliaro@va.gov
First Name & Middle Initial & Last Name or Official Title & Degree
William A Bauman, M.D.
Phone
718-584-9000
Ext
5428
Email
william.bauman@va.gov
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
William A Bauman, M.D.
Organizational Affiliation
James J. Peters VA Medical Center
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Steven C Kirshblum, M.D.
Organizational Affiliation
Kessler Institute for Rehabilitation
Official's Role
Principal Investigator
Facility Information:
Facility Name
Kessler Institute for Rehabilitation
City
West Orange
State/Province
New Jersey
ZIP/Postal Code
07052
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Christopher M Cirnigliaro, M.S.
Phone
973-731-3900
Ext
2755
Email
christopher.cirnigliaro@gmail.com
First Name & Middle Initial & Last Name & Degree
Steven C Kirshblum, M.D.
Phone
973-731-3900
Ext
2258
Email
skirshblum@kessler-rehab.com
First Name & Middle Initial & Last Name & Degree
Christopher M Cirnigliaro, M.S.
First Name & Middle Initial & Last Name & Degree
Steven C Kirshblum, M.D.
Facility Name
James J. Peters VA Medical Center
City
Bronx
State/Province
New York
ZIP/Postal Code
10468
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Joshua C Hobson, MS
Phone
718-584-9000
Ext
3129
Email
joshua.hobson@va.gov
First Name & Middle Initial & Last Name & Degree
Pierre Asselin, MS
Phone
718-584-9000
Ext
3124
Email
pierre.asselin@va.gov

12. IPD Sharing Statement

Citations:
PubMed Identifier
20533525
Citation
Reid IR, Miller PD, Brown JP, Kendler DL, Fahrleitner-Pammer A, Valter I, Maasalu K, Bolognese MA, Woodson G, Bone H, Ding B, Wagman RB, San Martin J, Ominsky MS, Dempster DW; Denosumab Phase 3 Bone Histology Study Group. Effects of denosumab on bone histomorphometry: the FREEDOM and STAND studies. J Bone Miner Res. 2010 Oct;25(10):2256-65. doi: 10.1002/jbmr.149.
Results Reference
background
PubMed Identifier
19594293
Citation
Kendler DL, Roux C, Benhamou CL, Brown JP, Lillestol M, Siddhanti S, Man HS, San Martin J, Bone HG. Effects of denosumab on bone mineral density and bone turnover in postmenopausal women transitioning from alendronate therapy. J Bone Miner Res. 2010 Jan;25(1):72-81. doi: 10.1359/jbmr.090716.
Results Reference
background
Links:
URL
http://www.scirc.org/
Description
Spinal Cord Damage Research Center

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Denosumab Administration After Spinal Cord Injury

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