The Efficacy of Denosumab in Incomplete Patients Spinal Cord Injury

March 13, 2024 updated by: William A. Bauman, M.D., James J. Peters Veterans Affairs Medical Center

The Efficacy of Denosumab to Prevent Bone Loss in Ambulatory and Non-ambulatory Motor-Incomplete Patients With Subacute Spinal Cord Injury

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

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

Interventional

Enrollment (Actual)

5

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • New Jersey
      • West Orange, New Jersey, United States, 07052
        • Kessler Institute for Rehabilitation
    • New York
      • Bronx, New York, United States, 10468
        • James J. Peters VA Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / 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 Names:
  • 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 Names:
  • 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
Prior to denosumab or placebo administration and 18 months after denosumab or placebo administration

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
Prior to denosumab or placebo administration and 12 months after denosumab or placebo administration

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

James J. Peters Veterans Affairs Medical Center

Collaborators

Kessler Institute for Rehabilitation

Investigators

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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 1, 2017

Primary Completion (Actual)

December 31, 2021

Study Completion (Actual)

October 6, 2022

Study Registration Dates

First Submitted

January 20, 2017

First Submitted That Met QC Criteria

January 20, 2017

First Posted (Estimated)

January 24, 2017

Study Record Updates

Last Update Posted (Actual)

March 15, 2024

Last Update Submitted That Met QC Criteria

March 13, 2024

Last Verified

March 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • BAU-16-057

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

An IPD is not desired by the investigators and is not part of the regulatory guidelines at the participating institutions

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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