Denosumab for Spinal Cord Injury

No longer recruiting at 2 trial locations

Overseen By William A Bauman, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: James J. Peters Veterans Affairs Medical Center

Must not be taking: Anabolic steroids, Bisphosphonates

Disqualifiers: Post-menopausal, Cancer, Hypocalcemia, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 6

Duration: 6 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether denosumab, a drug typically used to treat bone loss in certain conditions, can prevent bone loss in people with spinal cord injuries (SCI). The study compares denosumab injections to placebo (inactive saline solution) injections to assess their impact on bone health. It targets individuals with motor incomplete spinal cord injuries (partial loss of motor function) who have been injured for less than six months. Participants will attend six study visits over a year, each lasting 1 to 4.5 hours. As a Phase 4 trial, denosumab is already FDA-approved and proven effective, and this research aims to understand its benefits for more patients.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are on anabolic or steroid hormonal therapy, bisphosphonates, or high-dose corticosteroids, you may not be eligible to participate.

What is the safety track record for Denosumab?

Research has shown that denosumab is generally safe for use. The FDA has already approved it for treating conditions like osteoporosis and bone loss in cancer patients. Past studies found that denosumab helps maintain bone strength, indicating its effectiveness and safety.

However, some considerations are important. Some patients experienced multiple spine fractures after stopping denosumab, highlighting the need to follow a doctor's advice when ending treatment. While denosumab is considered safe for many, discussing any concerns with a healthcare provider remains crucial. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Denosumab is unique because it targets a specific protein involved in bone resorption, known as RANKL, which is different from the standard treatments for spinal cord injury that typically focus on nerve repair or rehabilitation. Unlike other treatments, Denosumab is a monoclonal antibody that can potentially reduce bone density loss, which is a common issue in patients with spinal cord injuries. Researchers are excited about Denosumab because it offers a new approach by addressing bone health directly, potentially improving overall patient outcomes in a way that current therapies do not.

What evidence suggests that denosumab might be an effective treatment for bone loss due to spinal cord injury?

Studies have shown that denosumab increases bone strength in people with spinal cord injuries. Research indicates that it helps maintain bone strength around the knee, especially in those with recent spinal cord injuries. One study found that after 24 months of treatment, denosumab improved bone strength in the lower back and thigh bone while reducing signs of bone loss. Denosumab is already used successfully to treat bone loss in people with osteoporosis and those undergoing cancer treatment. In this trial, some participants will receive denosumab, while others will receive a placebo. Its proven ability to strengthen bones and prevent fractures in other conditions suggests it could also be effective for people with spinal cord injuries. ^{1 4 5 6 7}

Who Is on the Research Team?

Steven C Kirshblum, M.D.

Principal Investigator

Kessler Institute for Rehabilitation

William A Bauman, M.D.

Principal Investigator

James J. Peters VA Medical Center

Are You a Good Fit for This Trial?

Inclusion Criteria

You have partial paralysis from a spinal cord injury.

Your injury happened less than 6 months ago.

Exclusion Criteria

Pregnancy

You have a serious long-term health condition.

Women who have already gone through menopause.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Denosumab or placebo injections at baseline and 6 months

6 months

3 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

3 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Denosumab

How Is the Trial Designed?

Group I: Denosumab, AIS Grade D (ambulatory) Experimental Treatment 1 Intervention

8 subjects with AIS grade D will be randomized to receive Denosumab (Prolia 120mg SC) administered at baseline and 6 months.

Group II: Denosumab, AIS Grade C (non-ambulatory) Experimental Treatment 1 Intervention

8 subjects with AIS grade C will be randomized to receive Denosumab (Prolia 120mg SC) administered at baseline and 6 months.

Group III: Placebo, AIS Grade D (ambulatory) Placebo Group 1 Intervention

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 IV: Placebo, AIS Grade C (non-ambulatory) Placebo Group 1 Intervention

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.

Denosumab is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Prolia for:

• Osteoporosis in postmenopausal women
• Bone loss associated with hormone ablation therapy for prostate cancer
• Bone loss associated with hormone ablation therapy for breast cancer

Approved in United States as Prolia for:

• Treatment of postmenopausal women with osteoporosis at high risk for fracture
• Treatment to increase bone mass in men at high risk for fracture receiving androgen deprivation therapy for nonmetastatic prostate cancer
• Treatment to increase bone mass in women at high risk for fracture receiving adjuvant aromatase inhibitor therapy for breast cancer

Approved in Canada as Prolia for:

• Treatment of osteoporosis in postmenopausal women at high risk for fracture
• Treatment to increase bone mass in men with osteoporosis at high risk for fracture

Approved in Japan as Prolia for:

• Treatment of osteoporosis in postmenopausal women
• Treatment of bone loss associated with hormone ablation therapy for prostate cancer

Who Is Running the Clinical Trial?

James J. Peters Veterans Affairs Medical Center

Lead Sponsor

Trials

59

Recruited

2,900+

Kessler Institute for Rehabilitation

Industry Sponsor

Trials

23

Recruited

1,100+

Published Research Related to This Trial

Denosumab, a monoclonal antibody that targets RANKL, significantly reduces the risk of fractures in postmenopausal women with osteoporosis, showing a 68% reduction in new vertebral fractures and a 40% reduction in hip fractures over a 3-year trial.

Long-term treatment with denosumab did not show increasing trends in adverse events, indicating that its safety profile remains stable over 6 years, even when comparing data from initial placebo recipients who later received the treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety Observations With 3 Years of Denosumab Exposure: Comparison Between Subjects Who Received Denosumab During the Randomized FREEDOM Trial and Subjects Who Crossed Over to Denosumab During the FREEDOM Extension. Watts, NB., Brown, JP., Papapoulos, S., et al.[2018]

Denosumab, a monoclonal antibody that inhibits RANKL, shows consistent pharmacokinetics across a large population of 1,076 subjects, including both healthy individuals and cancer patients, indicating its effectiveness in preventing osteoclast activation and survival.

The study found that after administering denosumab, over 95% of patients achieved more than 97% RANKL occupancy, suggesting that dosage adjustments based on body weight, age, race, or tumor type are unnecessary for patients with bone metastases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Population pharmacokinetic analysis of denosumab in patients with bone metastases from solid tumours. Gibiansky, L., Sutjandra, L., Doshi, S., et al.[2021]

A 72-year-old woman developed severe liver damage (submassive hepatic necrosis) after receiving denosumab, indicating a potential adverse drug reaction linked to immune response and cytokine induction.

The case highlights that RANKL inhibition by denosumab can lead to significant liver injury, as evidenced by elevated liver enzymes and proinflammatory cytokines, suggesting careful monitoring is needed for patients receiving this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Severe hepatocytotoxicity linked to denosumab. Malnick, S., Maor, Y., Melzer, E., et al.[2018]

Denosumab is a novel antiresorptive drug approved in the UK for preventing osteoporotic fractures in postmenopausal women and for managing skeletal-related events in patients with bone metastases.

There is a risk of osteonecrosis of the jaw (ARONJ) associated with denosumab, which dental professionals need to consider when advising patients undergoing dental treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Denosumab, an Alternative to Bisphosphonates but also Associated with Osteonecrosis of the Jaw--What is the Risk?. Sidhu, HK.[2018]

Denosumab, a drug used to prevent bone loss, was linked to a non-healing area in the lower jaw after a tooth extraction, highlighting a potential complication associated with its use.

After stopping denosumab, the non-healing area healed successfully, suggesting that discontinuation of the drug may be necessary to allow for healing in similar cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Denosumab: a case of MRONJ with resolution. Lyttle, CV., Patterson, H.[2018]

Denosumab, a medication used to prevent osteoporosis in patients with low bone mineral density, has been associated with rare cases of hepatotoxicity, including a newly reported case of immune-mediated liver injury in a 43-year-old woman after three years of treatment.

The patient's liver function tests showed significantly elevated levels of liver enzymes, indicating potential drug-induced liver injury, which was confirmed by a liver biopsy revealing chronic inflammation and interface hepatitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Denosumab-Induced Immune Hepatitis. Ostrovsky, V., Malnick, S., Ish-Shalom, S., et al.[2021]

Citations

1. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK349107/

DETAILED OUTCOME DATA - Denosumab (Prolia) - NCBI - NIH The primary outcome in the ADAMO study was the mean per cent change in lumbar spine BMD at 12 months.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7587457/

Administration of Denosumab Preserves Bone Mineral ... Administration of denosumab preserves bone mineral density at the knee in persons with subacute spinal cord injury: findings from a randomized clinical trial.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT01983475

Denosumab Administration After Spinal Cord Injury 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 ...

4. xgevahcp.com xgevahcp.com/efficacy/solid-tumor-clinical-trial

Solid Tumor Clinical Trial - XGEVA® (denosumab) for HCPs Superior prevention of bone complications with XGEVA. Proven to help patients with bone metastases from breast, prostate, and other types of solid tumors.

5. scielo.isciii.es scielo.isciii.es/pdf/romm/v14n2/en_1889-836X-romm-14-2-0088.pdf

Effect of treatment with denosumab for 24 months in ... Conclusions: Treatment with denosumab during 24 months increases lumbar and femoral BMD and decreases BTMs in patients with recent SCI.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8857591/

Experience with denosumab (XGEVA®) for prevention of ... To date, survival outcomes with denosumab have been similar to those with zoledronate in patients with solid tumors and BMs. In general, overall survival (OS) ...

7. xgevahcp.com xgevahcp.com/about-xgeva/burden-of-sres

Risk & Burden of Skeletal-Related Events (SRE) Multiple vertebral fractures (MVF) have been reported following discontinuation of treatment with denosumab. Patients at higher risk for MVF include those with ...