OsteoporosisPhase 4NCT01983475
Denosumab Administration After Spinal Cord Injury
A Phase 4 study testing Denosumab in people with Osteoporosis and Spinal Cord Injury, run by James J. Peters Veterans Affairs Medical Center at 2 sites in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Osteoporosis, Spinal Cord Injury
- What is being tested?
- Denosumab
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 24 participants
- Where
- 2 sitesUnited States
- Study dates
- Jan 2015to May 2020
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Complete motor SCI [American Spinal Injury Association Impairment Scale (AIS) grade A and B];
- Duration of injury <12 weeks; and
- Males between the ages of 18 and 65 years old and females between the ages of 18 and 50 years old.
Who cannot join
- 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;
Show all 17Show fewer
- Hyperthyroidism;
- Cushing's disease or syndrome;
- Severe underlying chronic disease;
- Heterotopic ossification of the knee region (HO limited to the hip region only will not exclude subject participation);
- History of chronic alcohol abuse;
- Diagnosis of Hypocalcemia;
- Pregnancy;
- Existing dental condition/dental infection
- Any patient taking a bisphosphonate for heterotopic ossification (HO);
- 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.
Trial locations and contacts
2 sites in 1 country.
United States2 sites, 2 recruiting
- Recruiting
James J. Peters VA Medical Center
The Bronx, New York, 10468
Joshua C Hobson, MS, 718-584-9000 ext. 3129, joshua.hobson@va.gov
Pierre Asselin, MS, 718-584-9000 ext. 3124, pierre.asselin@va.gov
- Recruiting
Kessler Institute for Rehabilitation
West Orange, New Jersey, 07052
Christopher M Cirnigliaro, M.S., 973-731-3900 ext. 2755, christopher.cirnigliaro@gmail.com
Steven C Kirshblum, M.D., 973-731-3900 ext. 2258, skirshblum@kessler-rehab.com
About this study
Official title: 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.
Read the 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.
- Conditions
- Osteoporosis, Spinal Cord Injury
- Being tested
- Denosumab, Placebo (identical Denosumab volume of normal saline)
- Keywords
- Spinal Cord Injury, Denosumab, Osteoporosis, Dual Energy X-ray Absorptiometry
- Medical subject headings
- Osteoporosis, Spinal Cord Injuries
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DenosumabDrug
Also called Prolia
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).
Placebo (identical Denosumab volume of normal saline)Drug
Also called Unknown at this time
The placebo group will receive the identical volume of normal saline at parallel time points.
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | A group of participants will be randomized to the placebo group and will receive the identical volume of normal saline at parallel time points. Receives: Drug: Placebo (identical Denosumab volume of normal saline) |
| Denosumab | Experimental | 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. Receives: Drug: Denosumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Bone mineral density (BMD) of the distal femur
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.
Measured: Baseline, 1, 3, 6, 12, and 18 months after Denosumab administration
Secondary outcomes (1)
Bone microarchitecture of the distal femur and proximal tibia.
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.
Measured: Baseline, 12, and 18 months after Denosumab administration
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Nov 2013 (estimated)
- Study startJan 2015
- Primary completionMay 2020 (estimated)
- Study completionMay 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for OsteoporosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 24 participants (estimated)
Sponsor and investigators
- Lead sponsor
- James J. Peters Veterans Affairs Medical Center
- Sponsor type
- US federal agency
- Collaborators
- Kessler Institute for Rehabilitation
- Responsible party
- Principal investigator, William A. Bauman, M.D., James J. Peters Veterans Affairs Medical Center
- Investigators
- William A Bauman, M.D., Principal investigator, James J. Peters VA Medical CenterSteven C Kirshblum, M.D., Principal investigator, Kessler Institute for Rehabilitation
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01983475
- Sponsor's protocol ID
- 113536
- Status last verified
- Mar 2019
- First submitted
- 6 Nov 2013
- Last updated
- 8 Mar 2019
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 20533525Kendler 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.
PubMed 19594293
Study at a glance
From the registry record, last updated by the sponsor on 8 Mar 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Efficacy of Denosumab to Reduce Osteoporosis After Spinal Cord Injury
- ClinicalTrials.gov ID
- NCT01983475
- Acronym / sponsor ID
- 113536
- Conditions
- Osteoporosis, Spinal Cord Injury
- Keywords
- Spinal Cord Injury, Denosumab, Osteoporosis, Dual Energy X-ray Absorptiometry
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 24 participants (estimated)
- Lead sponsor
- James J. Peters Veterans Affairs Medical CenterUS federal agency
- Collaborators
- Kessler Institute for Rehabilitation
- Study start
- Jan 2015
- Primary completion
- May 2020 (estimated)
- Study completion
- May 2020 (estimated)
- First posted
- 14 Nov 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: Placebo (identical Denosumab volume of normal saline)A group of participants will be randomized to the placebo group and will receive the identical volume of normal saline at parallel time points. |
| Denosumab | Experimental | Drug: DenosumabA 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. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Complete motor SCI [American Spinal Injury Association Impairment Scale (AIS) grade A and B];
- Duration of injury <12 weeks; and
- Males between the ages of 18 and 65 years old and females between the ages of 18 and 50 years old.
Key exclusion criteria (17 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DenosumabAlso: ProliaIn 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). | Drug | Denosumab |
| Placebo (identical Denosumab volume of normal saline)Also: Unknown at this timeThe placebo group will receive the identical volume of normal saline at parallel time points. | Drug | Placebo |
Primary outcome
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.
1 secondary outcome
Bone microarchitecture of the distal femur and proximal tibia.
Time frame: Baseline, 12, and 18 months after Denosumab administration
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Mar 2019.
- Background: PubMed 20533525Reid 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.
- Background: PubMed 19594293Kendler 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.
- Spinal Cord Damage Research CenterLink provided by the sponsor.
Related trials for Osteoporosis
Enrolling by invitationObservational study
GRACE II (General Retrospective Analysis of Commercial Experience With AGN1 LOEP)
Osteoporosis
RecruitingObservational study
Glucocorticoid-induced Osteoporosis in Patients With Chronic Inflammatory Rheumatic Diseases or Psoriasis
Osteoporosis, Inflammatory Rheumatism
Not yet recruiting
Exercise and Fall Prevention for Fracture Reduction
Osteopenia, Osteoporosis
Active, not recruiting
Impact of Screening and Multicomponent Exercise on Fall Rates, Fractures, and Cardiovascular Health in Diabetes
Type 2 Diabetes, Osteoporosis
Recruiting
Surgeon-Initiated Bone Health Referral Pathway in Patients Undergoing Lower Extremity Arthroplasty
Osteoporosis, Arthroplasty Complications
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
William A Bauman, M.D. principal investigator
James J. Peters VA Medical Center
Steven C Kirshblum, M.D. principal investigator
Kessler Institute for Rehabilitation
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Denosumab in people with Osteoporosis and Spinal Cord Injury, run by James J. Peters Veterans Affairs Medical Center at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 8 Mar 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Christopher M Cirnigliaro, M.S. (973-731-3900 ext. 2755, christopher.cirnigliaro@va.gov), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Bone mineral density (BMD) of the distal femur (time frame: Baseline, 1, 3, 6, 12, and 18 months after Denosumab administration). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01983475, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Mar 2019.