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

Primary Purpose

Osteoporosis, Renal Osteodystrophy, Kidney Transplant; Complications

Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Denosumab Inj 60 mg/ml
Placebo
Sponsored by
Thomas Nickolas, MD MS
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Osteoporosis focused on measuring Denosumab, Bone density, Kidney transplant, Prolia

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Northwestern University, Feinburg School of Medicine
  • NorthShore University HealthSystem
  • Columbia University Medical Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Active drug

Placebo

Arm Description

Denosumab 60 mg subcutaneous injection every 6 months for 12 months (i.e., 2 injections)

Placebo subcutaneous injection every 6 months for 12 months (i.e., 2 injections)

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Full Information

First Posted
May 21, 2019
Last Updated
April 8, 2022
Sponsor
Thomas Nickolas, MD MS
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1. Study Identification

Unique Protocol Identification Number
NCT03960554
Brief Title
The Effects of 12-months of Denosumab on Bone Density in Prevalent Kidney Transplant Recipients
Acronym
ProliaKTx
Official Title
The Effects of 12-months of Denosumab on Bone Density, Quality and Strength in Prevalent Kidney Transplant Recipients
Study Type
Interventional

2. Study Status

Record Verification Date
April 2022
Overall Recruitment Status
Terminated
Why Stopped
Study lost funding
Study Start Date
January 16, 2020 (Actual)
Primary Completion Date
December 2, 2021 (Actual)
Study Completion Date
December 2, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Thomas Nickolas, MD MS

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Osteoporosis, Renal Osteodystrophy, Kidney Transplant; Complications
Keywords
Denosumab, Bone density, Kidney transplant, Prolia

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Masking Description
The investigators and clinical research coordinators will be blinded to treatment assignment for the duration of the study.
Allocation
Randomized
Enrollment
15 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Active drug
Arm Type
Active Comparator
Arm Description
Denosumab 60 mg subcutaneous injection every 6 months for 12 months (i.e., 2 injections)
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo subcutaneous injection every 6 months for 12 months (i.e., 2 injections)
Intervention Type
Drug
Intervention Name(s)
Denosumab Inj 60 mg/ml
Other Intervention Name(s)
Prolia
Intervention Description
Treatment will be administered by study personnel as a subcutaneous injection every 6-months for one year.
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
Placebo will be administered by study personnel as a subcutaneous injection every 6-months for one year.
Primary Outcome Measure Information:
Title
Bone mineral density (BMD) measured by dual energy X-ray absorptiometry (DXA)
Description
BMD will be measured to determine if 1-year of treatment with denosumab changes BMD as measured by DXA.
Time Frame
12 months
Title
Estimated bone strength measured by high resolution peripheral quantitative computed tomography (HR-pQCT) Imaging
Description
Estimated bone mechanical competence will be measured by HR-pQCT.
Time Frame
12 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Thomas Nickolas, MD, MS
Organizational Affiliation
Columbia University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Northwestern University, Feinburg School of Medicine
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
NorthShore University HealthSystem
City
Evanston
State/Province
Illinois
ZIP/Postal Code
60201
Country
United States
Facility Name
Columbia University Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

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