NCT03960554

The Effects of 12-months of Denosumab on Bone Density in Prevalent Kidney Transplant Recipients

The Effects of 12-months of Denosumab on Bone Density, Quality and Strength in Prevalent Kidney Transplant Recipients

• Status: Terminated
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 8 (actual)
• Sponsor: Thomas Nickolas, MD MS · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This is a Phase 2 Multi-Center Clinical Trial (safety and effectiveness trial) in 60 patients (40 denosumab; 20 placebo) who have had a kidney transplant for 12-months or longer with more than 30% of kidney function. The investigators will test whether denosumab safely improves bone mineral density (BMD) by dual-energy X-ray absorptiometry (DXA) and improves bone strength by high resolution peripheral quantitative computed tomography (HR-pQCT) in the subset of patients recruited at Columbia University Irving Medical Center. These data will inform the development and execution of a larger trial to test if denosumab prevents fractures in kidney transplant recipients.

Detailed description

Bone fractures are 3-times more common in kidney transplant recipients than in the general population and risk of dying after a hip fracture is 60% higher compared to kidney transplant recipients without a fracture. Unfortunately, there are no anti-fracture strategies that have been proven to be effective in double blinded randomized clinical trials for kidney transplant recipients. This is because some anti-fracture medications that are commonly used to treat osteoporosis and prevent fractures in the general population (i.e., bisphosphonates), may be harmful to the skeleton when kidney function is less than 30% of normal. In addition, intravenous bisphosphonates may be toxic to the kidneys, which further limits their utility in patients with a kidney transplant. Denosumab, a monoclonal antibody against RANKL, inhibits osteoclast function and is not harmful to the kidney. Denosumab prevents fractures in men and women with age-related and glucocorticoid-induced osteoporosis. Recently, a non-blinded randomized trial of denosumab versus usual care during the first year of kidney transplantation in 90 patients reported the bone mineral density (BMD) measured by dual energy X-ray absorptiometry (DXA) increased at the spine and hip and that bone strength measured by high resolution peripheral quantitative computed tomography (HR-pQCT) increased in patients treated with denosumab. Adverse events in denosumab-treated patients included greater risk of urinary tract infections, diarrhea, and transient levels of low serum calcium that were asymptomatic. This study demonstrated that denosumab safely increased BMD at the spine and hip in new kidney transplant recipients. However, long-term kidney recipients, who comprise the vast majority of patients living with a transplanted kidney and who are also at increased risk of fracture, were not included.

Conditions

• Osteoporosis
• Renal Osteodystrophy
• Kidney Transplant; Complications

Interventions

Type	Name	Description
DRUG	Denosumab Inj 60 mg/ml	Treatment will be administered by study personnel as a subcutaneous injection every 6-months for one year.
OTHER	Placebo	Placebo will be administered by study personnel as a subcutaneous injection every 6-months for one year.

Timeline

• Start date: 2020-01-16
• Primary completion: 2021-12-02
• Completion: 2021-12-02
• First posted: 2019-05-23
• Last updated: 2024-07-25
• Results posted: 2024-07-25

Locations

3 sites across 1 country: United States

Regulatory

• FDA-regulated drug study