Denosumab Administration After Spinal Cord Injury

• ClinicalTrials.gov Identifier: NCT01983475
• Recruitment Status: Unknown
• First Posted: November 14, 2013
• Last Update Posted: March 8, 2019
• Sponsor: James J. Peters Veterans Affairs Medical Center
• Collaborator: Kessler Institute for Rehabilitation
• Information provided by (Responsible Party): William A. Bauman, M.D., James J. Peters Veterans Affairs Medical Center

Tracking Information

• First Submitted Date: November 6, 2013
• First Posted Date: November 14, 2013
• Last Update Posted Date: March 8, 2019
• Study Start Date: January 2015
• Estimated Primary Completion Date: May 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 13, 2014)

Bone mineral density (BMD) of the distal femur [ Time Frame: Baseline, 1, 3, 6, 12, and 18 months after Denosumab administration ]

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.

Original Primary Outcome Measures (submitted: November 6, 2013)

Dual Energy X-ray Absorptiometry [ Time Frame: Baseline, 1, 3, 6, 12, and 18 motnhs after Denosumab administration ]

Change in BMD at the distal femur from baseline to 18 months after Denosumab administration is the primary outcome measure.

Current Secondary Outcome Measures (submitted: March 13, 2014)

Bone microarchitecture of the distal femur and proximal tibia. [ Time Frame: Baseline, 12, and 18 months after Denosumab administration ]

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.

Original Secondary Outcome Measures (submitted: November 6, 2013)

Peripheral Quantitative Computerized Tomography (pQCT) [ Time Frame: Baseline, 12, and 18 months after Denosumab administration ]

A secondary outcome measure is to test the efficacy of Denosumab to prevent deterioration of the microarchitecture of trabecular bone at the distal femur, proximal tibia, and distal tibia as determined by peripheral pQCT

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Denosumab Administration After Spinal Cord Injury
• Official Title: The Efficacy of Denosumab to Reduce Osteoporosis After Spinal Cord Injury
• 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.

• Study Type: Interventional
• Study Phase: Phase 4
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Investigator, Outcomes Assessor); Primary Purpose: Treatment

Condition

• Osteoporosis
• Spinal Cord Injury

Intervention

• Drug: Denosumab
  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).
  Other Name: Prolia
• Drug: Placebo (identical Denosumab volume of normal saline)
  The placebo group will receive the identical volume of normal saline at parallel time points.
  Other Name: Unknown at this time

Study Arms

• Placebo Comparator: Placebo
  A group of participants will be randomized to the placebo group and will receive the identical volume of normal saline at parallel time points.
  Intervention: Drug: Placebo (identical Denosumab volume of normal saline)
• Experimental: Denosumab
  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: Drug: Denosumab

Publications *

• 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.
• 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.

Recruitment Information

• Recruitment Status: Unknown status
• Estimated Enrollment (submitted: November 6, 2013): 24
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: May 2020
• Estimated Primary Completion Date: May 2020 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 65 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT01983475
• Other Study ID Numbers: 113536
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: William A. Bauman, M.D., James J. Peters Veterans Affairs Medical Center
• Original Responsible Party: William Bauman, US Department of Veterans Affairs, Director VA RR&D Center of Excellence for the Medical Consequences of SCI
• Current Study Sponsor: James J. Peters Veterans Affairs Medical Center
• Original Study Sponsor: US Department of Veterans Affairs
• Collaborators: Kessler Institute for Rehabilitation

Investigators

• Principal Investigator: William A Bauman, M.D.; James J. Peters VA Medical Center
• Principal Investigator: Steven C Kirshblum, M.D.; Kessler Institute for Rehabilitation

• PRS Account: James J. Peters Veterans Affairs Medical Center
• Verification Date: March 2019