Denosumab Administration After Spinal Cord Injury

James J. Peters Veterans Affairs Medical Center

Status and phase: Unknown; Phase 4

Conditions: Osteoporosis; Spinal Cord Injury

Treatments: Drug: Placebo (identical Denosumab volume of normal saline); Drug: Denosumab

Study type: Interventional

Funder types: Other U.S. Federal agency; Industry

Identifiers

NCT01983475

113536

Details and patient eligibility

About

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.

Full 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.

Enrollment: 24 estimated patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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24 participants in 2 patient groups, including a placebo group

Placebo

Placebo Comparator group

Description:

A group of participants will be randomized to the placebo group and will receive the identical volume of normal saline at parallel time points.

Treatment:

Drug: Placebo (identical Denosumab volume of normal saline)

Denosumab

Experimental group

Description:

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.

Treatment:

Drug: Denosumab