Denosumab Administration After Spinal Cord Injury
The Efficacy of Denosumab to Reduce Osteoporosis After Spinal Cord Injury
1 other identifier
interventional
24
1 country
2
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_4
Started Jan 2015
Longer than P75 for phase_4
2 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
November 6, 2013
CompletedFirst Posted
Study publicly available on registry
November 14, 2013
CompletedStudy Start
First participant enrolled
January 1, 2015
CompletedPrimary Completion
Last participant's last visit for primary outcome
May 1, 2020
CompletedStudy Completion
Last participant's last visit for all outcomes
May 1, 2020
CompletedMarch 8, 2019
March 1, 2019
5.3 years
November 6, 2013
March 6, 2019
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
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.
Baseline, 1, 3, 6, 12, and 18 months after Denosumab administration
Secondary Outcomes (1)
Bone microarchitecture of the distal femur and proximal tibia.
Baseline, 12, and 18 months after Denosumab administration
Study Arms (2)
Placebo
PLACEBO COMPARATORA group of participants will be randomized to the placebo group and will receive the identical volume of normal saline at parallel time points.
Denosumab
EXPERIMENTALA 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.
Interventions
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).
The placebo group will receive the identical volume of normal saline at parallel time points.
Eligibility Criteria
You may qualify if:
- 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.
You may not qualify if:
- 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);
- +2 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (2)
Kessler Institute for Rehabilitation
West Orange, New Jersey, 07052, United States
James J. Peters VA Medical Center
The Bronx, New York, 10468, United States
Related Publications (2)
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.
PMID: 20533525BACKGROUNDKendler 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.
PMID: 19594293BACKGROUND
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
William A Bauman, M.D.
James J. Peters VA Medical Center
- PRINCIPAL INVESTIGATOR
Steven C Kirshblum, M.D.
Kessler Institute for Rehabilitation
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 4
- Allocation
- RANDOMIZED
- Masking
- TRIPLE
- Who Masked
- PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- FED
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Director VA RR&D Center of Excellence for the Medical Consequences of SCI
Study Record Dates
First Submitted
November 6, 2013
First Posted
November 14, 2013
Study Start
January 1, 2015
Primary Completion
May 1, 2020
Study Completion
May 1, 2020
Last Updated
March 8, 2019
Record last verified: 2019-03