Denosumab Administration After Spinal Cord Injury

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified March 2014 by James J. Peters Veterans Affairs Medical Center
Sponsor:
Collaborator:
Kessler Institute for Rehabilitation
Information provided by (Responsible Party):
William A. Bauman, M.D., James J. Peters Veterans Affairs Medical Center
ClinicalTrials.gov Identifier:
NCT01983475
First received: November 6, 2013
Last updated: July 17, 2014
Last verified: March 2014
  Purpose

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.


Condition Intervention Phase
Osteoporosis
Spinal Cord Injury
Drug: Denosumab
Drug: Placebo (identical Densoumab volume of normal saline)
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: The Efficacy of Denosumab to Reduce Osteoporosis After Spinal Cord Injury

Resource links provided by NLM:


Further study details as provided by James J. Peters Veterans Affairs Medical Center:

Primary Outcome Measures:
  • Bone mineral density (BMD) of the distal femur [ Time Frame: Baseline, 1, 3, 6, 12, and 18 months after Denosumab administration ] [ Designated as safety issue: No ]
    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. [ Time Frame: Baseline, 12, and 18 months after Denosumab administration ] [ Designated as safety issue: No ]
    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.


Estimated Enrollment: 24
Study Start Date: April 2014
Estimated Study Completion Date: May 2018
Estimated Primary Completion Date: May 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Drug: Placebo (identical Densoumab 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
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.
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

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.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01983475

Contacts
Contact: Christopher M Cirnigliaro, M.S. 973-731-3900 ext 2755 christopher.cirnigliaro@va.gov
Contact: William A Bauman, M.D. 718-584-9000 ext 5428 william.bauman@va.gov

Locations
United States, New Jersey
Kessler Institute for Rehabilitation Not yet recruiting
West Orange, New Jersey, United States, 07052
Contact: Christopher M Cirnigliaro, M.S.    973-731-3900 ext 2755    christopher.cirnigliaro@gmail.com   
Contact: Steven C Kirshblum, M.D.    973-731-3900 ext 2258    skirshblum@kessler-rehab.com   
Sub-Investigator: Christopher M Cirnigliaro, M.S.         
Principal Investigator: Steven C Kirshblum, M.D.         
Sponsors and Collaborators
James J. Peters Veterans Affairs Medical Center
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
  More Information

Additional Information:
Publications:
Responsible Party: William A. Bauman, M.D., Director VA RR&D Center of Excellence for the Medical Consequences of SCI, James J. Peters Veterans Affairs Medical Center
ClinicalTrials.gov Identifier: NCT01983475     History of Changes
Other Study ID Numbers: 113536
Study First Received: November 6, 2013
Last Updated: July 17, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by James J. Peters Veterans Affairs Medical Center:
Spinal Cord Injury
Denosumab
Osteoporosis
Dual Energy X-ray Absorptiometry

Additional relevant MeSH terms:
Osteoporosis
Spinal Cord Injuries
Wounds and Injuries
Bone Diseases, Metabolic
Bone Diseases
Musculoskeletal Diseases
Spinal Cord Diseases
Central Nervous System Diseases
Nervous System Diseases
Trauma, Nervous System

ClinicalTrials.gov processed this record on August 21, 2014