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The Efficacy of Denosumab in Incomplete Patients Spinal Cord Injury

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ClinicalTrials.gov Identifier: NCT03029442
Recruitment Status : Recruiting
First Posted : January 24, 2017
Last Update Posted : March 8, 2019
Sponsor:
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  ICMJE January 20, 2017
First Posted Date  ICMJE January 24, 2017
Last Update Posted Date March 8, 2019
Actual Study Start Date  ICMJE April 1, 2017
Estimated Primary Completion Date December 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 20, 2017)
areal bone mineral density (aBMD) by dual energy X-ray absorptiometry (DXA) [ Time Frame: Prior to denosumab or placebo administration and 18 months after denosumab or placebo administration ]
Efficacy of denosumab to prevent aBMD loss at the distal femur and proximal tibia
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03029442 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: January 20, 2017)
volumetric BMD (vBMD) and microarchitecture by peripheral quantitative computed tomography [ Time Frame: Prior to denosumab or placebo administration and 12 months after denosumab or placebo administration ]
Efficacy of denosumab to prevent vBMD loss and microarchitecture deterioration at the distal femur and proximal tibia
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE The Efficacy of Denosumab in Incomplete Patients Spinal Cord Injury
Official Title  ICMJE The Efficacy of Denosumab to Prevent Bone Loss in Ambulatory and Non-ambulatory Motor-Incomplete Patients With Subacute Spinal Cord Injury
Brief Summary The purpose of this study is to determine the usefulness of a drug, denosumab, to prevent the loss of bone in participants legs due to SCI. This drug is FDA approved to treat osteoporosis in women after menopause who have an increased risk for fractures, to treat women receiving certain treatments for breast cancer who have an increased risk of fractures, and to treat bone loss in men receiving certain treatments for prostate cancer who have increased risk for fractures. This drug is considered experimental for the purpose of this study. Study participation will last for approximately 12 months (6 study visits total), visits will range from1-4.5 hours depending on the number of tests that need to be completed. The study is a double-blinded placebo trail in which the participant will be randomly assigned to on of two groups, Denosumab injections or placebo - inactive salt solution injections.
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 subacute motor-incomplete SCI [American Spinal Injury Association (AIS) neurological classification scale C and D] at the James J. Peters VA Medical Center (JJPVAMC) and Kessler Institute for Rehabilitation (KIR). A randomized, double-blind, placebo-controlled, parallel group trial will be performed in thirty-two subjects with acute, motor-incomplete SCI (≤6 months) who have been admitted to JJPVAMC or the KIR. Denosumab (60 mg SC) will be administered at baseline, 6, and 12 months; the placebo group will receive normal saline subcutaneously. Denosumab will be administered as soon as possible, but up to 24 weeks, after SCI. The last dose of denosumab and placebo will be administered at 6 months, with the anticipated effect of the drug to persist and inhibit bone resorption at least until the 12 month time point.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Secondary Osteoporosis
  • Spinal Cord Injury
Intervention  ICMJE
  • Drug: Denosumab (Prolia)
    In clinical trials, denosumab (Amgen Inc., Thousand Oaks, CA), has been shown to be more potent in reducing osteoclastosis and function than bisphosphonates. 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: Xgeva
  • Other: Placebo (normal saline)
    Identical Denosumab volume of normal saline
Study Arms  ICMJE
  • Experimental: Denosumab, AIS Grade C (non-ambulatory)
    8 subjects with AIS grade C will be randomized to receive Denosumab (Prolia 120mg SC) administered at baseline and 6 months.
    Intervention: Drug: Denosumab (Prolia)
  • Placebo Comparator: Placebo, AIS Grade C (non-ambulatory)
    8 subjects with AIS grade C will be randomized to the placebo group and will receive the identical volume of normal saline at parallel time points.
    Intervention: Other: Placebo (normal saline)
  • Experimental: Denosumab, AIS Grade D (ambulatory)
    8 subjects with AIS grade D will be randomized to receive Denosumab (Prolia 120mg SC) administered at baseline and 6 months.
    Intervention: Drug: Denosumab (Prolia)
  • Placebo Comparator: Placebo, AIS Grade D (ambulatory)
    8 subjects with AIS grade D will be randomized to the placebo group and will receive the identical volume of normal saline at parallel time points.
    Intervention: Other: Placebo (normal saline)
Publications * Gifre L, Vidal J, Carrasco JL, Muxi A, Portell E, Monegal A, Guañabens N, Peris P. Denosumab increases sublesional bone mass in osteoporotic individuals with recent spinal cord injury. Osteoporos Int. 2016 Jan;27(1):405-10. doi: 10.1007/s00198-015-3333-5. Epub 2015 Sep 30.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: January 20, 2017)
32
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2023
Estimated Primary Completion Date December 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Motor incomplete SCI [American Spinal Injury Association Impairment Scale (AIS) grades C and D];
  2. Duration of injury < 6-months; 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. History of chronic alcohol abuse;
  11. Diagnosis of Hypocalcemia;
  12. Pregnancy;
  13. Existing dental condition/dental infection;
  14. Diagnosis of heterotopic ossification at the hip and/or knee region and receiving a bisphosphonates [e.g. alendronate sodium (Fosamax) or etidronate disodium (Didronel)] that will no longer make participants eligible to receive the study medication/placebo but are still eligible to complete follow-up outcome measures as described in the work schedule;
  15. Current diagnosis of cancer or history of cancer; and
  16. 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  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
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
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03029442
Other Study ID Numbers  ICMJE BAU-16-057
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Plan Description: An IPD is not desired by the investigators and is not part of the regulatory guidelines at the participating institutions
Responsible Party William A. Bauman, M.D., James J. Peters Veterans Affairs Medical Center
Study Sponsor  ICMJE James J. Peters Veterans Affairs Medical Center
Collaborators  ICMJE Kessler Institute for Rehabilitation
Investigators  ICMJE
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

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP