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

April 8, 2022 updated by: Thomas Nickolas, MD MS

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

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

15

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Northwestern University, Feinburg School of Medicine
      • Evanston, Illinois, United States, 60201
        • NorthShore University HealthSystem
    • New York
      • New York, New York, United States, 10032
        • Columbia University Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion criteria

  1. Men and women
  2. All race-ethnicities
  3. Age ≥ 18 years
  4. ≥ 12-months after kidney transplantation (living or deceased donor recipient)

  5. Stable allograft function over the previous year defined as:

    1. No rejections
    2. No more than a 15% decline in Glomerular filtration rate (GFR) over the prior year
  6. Allograft GFR ≥ 30 mL/minute/1.73 m2 (MDRD or Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) per local lab reporting)
  7. 25OHD ≥ 30 ng/mL (determined at screening visit)
  8. Serum calcium ≥ 9.0 mg/dL (determined at screening visit)
  9. T-Score at the spine including and between -1.0 and -3.5 (determined at screening visit)
  10. Must have had a routine dental exam within 6-months of study recruitment
  11. Must agree to continue with routine dental exams over the course of the study
  12. Has not undergone an invasive dental procedure (i.e., tooth extraction, dental implants, oral surgery) within ≤ 3-months of recruitment
  13. Must agree to referral to metabolic bone disease specialist at the end of the study
  14. Women of child bearing potential must be willing to use one form of effective contraception over the course of the study

Exclusion Criteria

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Active drug
Denosumab 60 mg subcutaneous injection every 6 months for 12 months (i.e., 2 injections)
Drug: Denosumab Inj 60 mg/ml
Treatment will be administered by study personnel as a subcutaneous injection every 6-months for one year.
Other Names:
  • Prolia
Placebo Comparator: Placebo
Placebo subcutaneous injection every 6 months for 12 months (i.e., 2 injections)
Other: Placebo
Placebo will be administered by study personnel as a subcutaneous injection every 6-months for one year.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Bone mineral density (BMD) measured by dual energy X-ray absorptiometry (DXA)
Time Frame: 12 months
BMD will be measured to determine if 1-year of treatment with denosumab changes BMD as measured by DXA.
12 months
Estimated bone strength measured by high resolution peripheral quantitative computed tomography (HR-pQCT) Imaging
Time Frame: 12 months
Estimated bone mechanical competence will be measured by HR-pQCT.
12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Thomas Nickolas, MD MS

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 16, 2020

Primary Completion (Actual)

December 2, 2021

Study Completion (Actual)

December 2, 2021

Study Registration Dates

First Submitted

May 21, 2019

First Submitted That Met QC Criteria

May 21, 2019

First Posted (Actual)

May 23, 2019

Study Record Updates

Last Update Posted (Actual)

April 15, 2022

Last Update Submitted That Met QC Criteria

April 8, 2022

Last Verified

April 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AAAS3103

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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