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

  • STATUS
    Recruiting
  • End date
    Jun 22, 2022
  • participants needed
    60
  • sponsor
    Thomas Nickolas, MD MS
Updated on 22 July 2021
calcium
kidney transplant
tooth extraction
x-rays
denosumab
bone mineral density
metabolic bone disease
dental procedure
dual-energy x-ray absorptiometry
quantitative computed tomography
osteopathy
kidney disease
oral surgery
x-ray absorptiometry

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.

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.

Details
Condition Osteopenia, Renal Osteodystrophy, Osteoporosis, Kidney Transplant; Complications, Kidney Transplant; Complications, Kidney Transplant; Complications, Kidney Transplant; Complications, Kidney Transplant; Complications
Treatment Placebo, Denosumab Inj 60 mg/ml
Clinical Study IdentifierNCT03960554
SponsorThomas Nickolas, MD MS
Last Modified on22 July 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

Men and women
All race-ethnicities
Age 18 years
12-months after kidney transplantation (living or deceased donor recipient)
Stable allograft function over the previous year defined as
No rejections
No more than a 15% decline in Glomerular filtration rate (GFR) over the prior year
Allograft GFR 30 mL/minute/1.73 m2 (MDRD or Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) per local lab reporting)
25OHD 30 ng/mL (determined at screening visit)
Serum calcium 9.0 mg/dL (determined at screening visit)
T-Score at the spine including and between -1.0 and -3.5 (determined at screening visit)
Must have had a routine dental exam within 6-months of study recruitment
Must agree to continue with routine dental exams over the course of the study
Has not undergone an invasive dental procedure (i.e., tooth extraction, dental implants, oral surgery) within 3-months of recruitment
Must agree to referral to metabolic bone disease specialist at the end of the study
Women of child bearing potential must be willing to use one form of effective contraception over the course of the study

Exclusion Criteria

Allograft GFR < 30 mL/minute/1.73 m2 (MDRD or CKD-EPI per local lab reporting)
Within 24-months of starting renal replacement therapy
Prevalent or occult vertebral fractures
History of post-transplantation non-basal cell carcinoma cancers
Non-ambulatory
Malignancy requiring chemotherapy or metastatic to bone
Non-transplant related metabolic bone diseases that alter bone mineral density, including but not limited to Primary hyperparathyroidism, Paget's, Osteogenesis Imperfecta
Within one-year of parathyroidectomy
Untreated hyperthyroidism for 6-months or longer
Untreated hypothyroidism for 6-months of longer
Medical diseases (end stage liver, lung or heart, intestinal malabsorption)
Use within the prior year of bisphosphonates, teriparatide, selective estrogen receptor modulators, testosterone, estrogen, denosumab, abaloparatide, calcitonin, and romosozumab
Allergy to components within the denosumab preparation or to denosumab
Weight > 300 pounds
Parathyroid hormone (PTH) > 450 pg /mL
Will undergo an invasive dental procedure (i.e., tooth extraction, dental implants, oral surgery) within the next 12-months
Pregnant
Planned pregnancy during the course of the study
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