The Efficacy of Denosumab in Incomplete Patients Spinal Cord Injury

NCT ID: NCT03029442

Last Updated: 2024-03-15

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE4
• Total Enrollment: 5 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-04-01
• Study Completion Date: 2022-10-06

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.

Conditions

Secondary Osteoporosis; Spinal Cord Injury

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

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.

Group Type: EXPERIMENTAL

Denosumab (Prolia)

Intervention Type: DRUG

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).

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.

Group Type: PLACEBO_COMPARATOR

Placebo (normal saline)

Intervention Type: OTHER

Identical Denosumab volume of normal saline

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.

Group Type: EXPERIMENTAL

Denosumab (Prolia)

Intervention Type: DRUG

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).

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.

Group Type: PLACEBO_COMPARATOR

Placebo (normal saline)

Intervention Type: OTHER

Identical Denosumab volume of normal saline

Interventions

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).

Intervention Type: DRUG

Placebo (normal saline)

Identical Denosumab volume of normal saline

Intervention Type: OTHER

Other Intervention Names

Xgeva

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Kessler Institute for Rehabilitation

INDUSTRY

Sponsor Role: collaborator

James J. Peters Veterans Affairs Medical Center

FED

Sponsor Role: lead

Responsible Party

William A. Bauman, M.D.

Director, Clinical Investigator, National Center of Excellence for the Medical Consequences of Spinal Cord Injury

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

William A Bauman, M.D.

Role: PRINCIPAL_INVESTIGATOR

James J. Peters VA Medical Center

Steven C Kirshblum, M.D.

Role: PRINCIPAL_INVESTIGATOR

Kessler Institute for Rehabilitation

Locations

Kessler Institute for Rehabilitation

West Orange, New Jersey, United States

James J. Peters VA Medical Center

The Bronx, New York, United States

Countries

United States

References

Gifre L, Vidal J, Carrasco JL, Muxi A, Portell E, Monegal A, Guanabens 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.

Reference Type: BACKGROUND

PMID: 26423406 (View on PubMed)

Other Identifiers

BAU-16-057

Identifier Type: -

Identifier Source: org_study_id