Denosumab Administration After Spinal Cord Injury

March 6, 2019 updated by: William A. Bauman, M.D., James J. Peters Veterans Affairs Medical Center

The Efficacy of Denosumab to Reduce Osteoporosis After Spinal Cord Injury

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.

Study Overview

Status

Unknown

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 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

Enrollment (Anticipated)

24

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
        • Recruiting
        • Kessler Institute for Rehabilitation
        • Sub-Investigator:
          • Christopher M Cirnigliaro, M.S.
    • New York
      • Bronx, New York, United States, 10468
        • Recruiting
        • James J. Peters VA Medical Center
        • Contact:
        • Contact:

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

Genders Eligible for Study

All

Description

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.

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
  • Masking: TRIPLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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 Denosumab volume of normal saline)
The placebo group will receive the identical volume of normal saline at parallel time points.
Other Names:
  • 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 Names:
  • Prolia

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Baseline, 1, 3, 6, 12, and 18 months after Denosumab administration

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Baseline, 12, and 18 months after Denosumab 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

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

Helpful Links

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

January 1, 2015

Primary Completion (ANTICIPATED)

May 1, 2020

Study Completion (ANTICIPATED)

May 1, 2020

Study Registration Dates

First Submitted

November 6, 2013

First Submitted That Met QC Criteria

November 6, 2013

First Posted (ESTIMATE)

November 14, 2013

Study Record Updates

Last Update Posted (ACTUAL)

March 8, 2019

Last Update Submitted That Met QC Criteria

March 6, 2019

Last Verified

March 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 113536

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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