The Efficacy of Denosumab to Prevent Bone Loss in Ambulatory and Non-ambulatory Motor-Incomplete Patients With Subacute Spinal Cord Injury
Trial Snapshot
- Phase
- Phase 4
- Status
- Terminated
- Sponsor
- Enrollment
- 5
- Locations
- 2
- Primary Endpoint
- areal bone mineral density (aBMD) by dual energy X-ray absorptiometry (DXA)
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Triple (Participant, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to 65 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Motor incomplete SCI [American Spinal Injury Association Impairment Scale (AIS) grades C and D];
- •Duration of injury < 6-months; and
- •Males between the ages of 18 and 65 years old and females between the ages of 18 and 50 years old.
Exclusion Criteria
- •Extensive life-threatening injuries in addition to SCI;
- •Acute fracture or extensive bone trauma;
- •History of prior bone disease (Paget's hyperparathyroidism, osteoporosis, etc.)
- •Post-menopausal women;
- •Men with known hypogonadism prior to SCI;
- •Anabolic or Steroid hormonal therapy; within the past year and longer than six months;
- •Hyperthyroidism;
- •Cushing's disease or syndrome;
- •Severe underlying chronic disease;
- •History of chronic alcohol abuse;
- •Diagnosis of Hypocalcemia;
- •Existing dental condition/dental infection;
- •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;
- •Current diagnosis of cancer or history of cancer; and
- •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.
Arms & Interventions
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.
Intervention: Denosumab (Prolia) (Drug)
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.
Intervention: Placebo (normal saline) (Other)
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.
Intervention: Denosumab (Prolia) (Drug)
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.
Intervention: Placebo (normal saline) (Other)
Outcomes
Primary Outcomes
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 Outcomes
- volumetric BMD (vBMD) and microarchitecture by peripheral quantitative computed tomography(Prior to denosumab or placebo administration and 12 months after denosumab or placebo administration)
Investigators
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