Denosumab Administration After Spinal Cord Injury

NCT ID: NCT01983475

Last Updated: 2019-03-08

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE4

Total Enrollment

24 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-01-31

Study Completion Date

2020-05-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Osteoporosis Spinal Cord Injury

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Investigators Outcome Assessors

Study Groups

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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.

Group Type PLACEBO_COMPARATOR

Placebo (identical Denosumab volume of normal saline)

Intervention Type DRUG

The placebo group will receive the identical volume of normal saline at parallel time points.

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.

Group Type EXPERIMENTAL

Denosumab

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.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).

Interventions

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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).

Intervention Type DRUG

Placebo (identical Denosumab volume of normal saline)

The placebo group will receive the identical volume of normal saline at parallel time points.

Intervention Type DRUG

Other Intervention Names

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Prolia Unknown at this time

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Kessler Institute for Rehabilitation

INDUSTRY

Sponsor Role collaborator

James J. Peters Veterans Affairs Medical Center

FED

Sponsor Role lead

Responsible Party

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William A. Bauman, M.D.

Director VA RR&D Center of Excellence for the Medical Consequences of SCI

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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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

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Kessler Institute for Rehabilitation

West Orange, New Jersey, United States

Site Status RECRUITING

James J. Peters VA Medical Center

The Bronx, New York, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Christopher M Cirnigliaro, M.S.

Role: CONTACT

973-731-3900 ext. 2755

William A Bauman, M.D.

Role: CONTACT

718-584-9000 ext. 5428

Facility Contacts

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Christopher M Cirnigliaro, M.S.

Role: primary

973-731-3900 ext. 2755

Steven C Kirshblum, M.D.

Role: backup

973-731-3900 ext. 2258

Joshua C Hobson, MS

Role: primary

718-584-9000 ext. 3129

Pierre Asselin, MS

Role: backup

718-584-9000 ext. 3124

References

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Reid IR, Miller PD, Brown JP, Kendler DL, Fahrleitner-Pammer A, Valter I, Maasalu K, Bolognese MA, Woodson G, Bone H, Ding B, Wagman RB, San Martin J, Ominsky MS, Dempster DW; Denosumab Phase 3 Bone Histology Study Group. Effects of denosumab on bone histomorphometry: the FREEDOM and STAND studies. J Bone Miner Res. 2010 Oct;25(10):2256-65. doi: 10.1002/jbmr.149.

Reference Type BACKGROUND
PMID: 20533525 (View on PubMed)

Kendler DL, Roux C, Benhamou CL, Brown JP, Lillestol M, Siddhanti S, Man HS, San Martin J, Bone HG. Effects of denosumab on bone mineral density and bone turnover in postmenopausal women transitioning from alendronate therapy. J Bone Miner Res. 2010 Jan;25(1):72-81. doi: 10.1359/jbmr.090716.

Reference Type BACKGROUND
PMID: 19594293 (View on PubMed)

Related Links

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http://www.scirc.org/

Spinal Cord Damage Research Center

Other Identifiers

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113536

Identifier Type: -

Identifier Source: org_study_id

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