The Efficacy of Denosumab in Incomplete Patients Spinal Cord Injury

• 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

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Secondary Osteoporosis; Spinal Cord Injury	Drug: Denosumab (Prolia); Other: Placebo (normal saline)	Phase 4

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 Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	32 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose:	Treatment
Official Title:	The Efficacy of Denosumab to Prevent Bone Loss in Ambulatory and Non-ambulatory Motor-Incomplete Patients With Subacute Spinal Cord Injury
Actual Study Start Date :	April 1, 2017
Estimated Primary Completion Date :	December 2021
Estimated Study Completion Date :	December 2023

Arms and Interventions

Arm	Intervention/treatment
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.	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
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.	Other: Placebo (normal saline); Identical Denosumab volume of 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.	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
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.	Other: Placebo (normal saline); Identical Denosumab volume of normal saline

Outcome Measures

Primary Outcome Measures :

1. 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

Secondary Outcome Measures :

1. 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

Eligibility Criteria

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Ages Eligible for Study:	18 Years to 65 Years (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

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.

Contacts and Locations

Contacts

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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

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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 Cirniliaro, M.S.
Principal Investigator: Steven C Kirshblum, M.D.
United States, New York
James J. Peters VA Medical Center	Recruiting
Bronx, New York, United States, 10468
Contact: Joshua C Hobson, M.S. 718-584-9000 ext 3129 joshua.hobson@va.gov

Sponsors and Collaborators

James J. Peters Veterans Affairs Medical Center

Kessler Institute for Rehabilitation

Investigators

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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

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.

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Responsible Party:	William A. Bauman, M.D., Director, Clinical Investigator, National Center of Excellence for the Medical Consequences of Spinal Cord Injury, James J. Peters Veterans Affairs Medical Center
ClinicalTrials.gov Identifier:	NCT03029442 History of Changes
Other Study ID Numbers:	BAU-16-057
First Posted:	January 24, 2017
Last Update Posted:	March 8, 2019
Last Verified:	March 2019
Individual Participant Data (IPD) Sharing Statement:
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

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Studies a U.S. FDA-regulated Drug Product:		Yes
Studies a U.S. FDA-regulated Device Product:		No

Keywords provided by William A. Bauman, M.D., James J. Peters Veterans Affairs Medical Center:

Spinal Cord Injury; Denosumab; Osteoporosis; Dual Energy X-ray Absorptiometry

Additional relevant MeSH terms:

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Wounds and Injuries; Osteoporosis; Spinal Cord Injuries; Bone Diseases, Metabolic; Bone Diseases; Musculoskeletal Diseases; Metabolic Diseases	Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Trauma, Nervous System; Denosumab; Bone Density Conservation Agents; Physiological Effects of Drugs