OsteoporosisPhase 2ProliaKTxNCT03960554
The Effects of 12-months of Denosumab on Bone Density in Prevalent Kidney Transplant Recipients
A Phase 2 study testing Denosumab Inj 60 mg/ml in people with Osteoporosis and Renal Osteodystrophy, run by Thomas Nickolas, MD MS at 3 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Osteoporosis, Renal Osteodystrophy, Kidney Transplant; Complications
- What is being tested?
- Denosumab Inj 60 mg/ml
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 8 participants
- Where
- 3 sitesUnited States
- Study dates
- 16 Jan 2020to 2 Dec 2021
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 16Show fewer
- 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
Who cannot join
- 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
Show all 18Show fewer
- 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
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Northwestern University, Feinburg School of Medicine
Chicago, Illinois, 60611
NorthShore University HealthSystem
Evanston, Illinois, 60201
Columbia University Medical Center
New York, New York, 10032
About this study
Official title: 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.
Read the 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.
- Being tested
- Denosumab Inj 60 mg/ml, Placebo
- Keywords
- Denosumab, Bone density, Kidney transplant, Prolia
- Medical subject headings
- Osteoporosis, Chronic Kidney Disease-Mineral and Bone Disorder
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Denosumab Inj 60 mg/mlDrug
Also called Prolia
Treatment will be administered by study personnel as a subcutaneous injection every 6-months for one year.
PlaceboOther
Placebo will be administered by study personnel as a subcutaneous injection every 6-months for one year.
| Study group | Role | What they receive |
|---|---|---|
| Active drug | Active comparator | Denosumab 60 mg subcutaneous injection every 6 months for 12 months (i.e., 2 injections) Receives: Drug: Denosumab Inj 60 mg/ml |
| Placebo | Placebo comparator | Placebo subcutaneous injection every 6 months for 12 months (i.e., 2 injections) Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 12 months
Estimated Bone Strength Measured by High Resolution Peripheral Quantitative Computed Tomography (HR-pQCT) Imaging
Estimated bone mechanical competence will be measured by HR-pQCT.
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 May 2019
- Study start16 Jan 2020
- Primary completion2 Dec 2021
- Study completion2 Dec 2021
Why it stopped: Study lost funding
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for OsteoporosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 8 participants (actual)
Sponsor and investigators
- Lead sponsor
- Thomas Nickolas, MD MS
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Thomas Nickolas, MD MS, Columbia University
- Investigators
- Thomas Nickolas, MD, MS, Principal investigator, Columbia University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03960554
- Sponsor's protocol ID
- AAAS3103
- Acronym
- ProliaKTx
- Status last verified
- Jul 2024
- First submitted
- 21 May 2019
- Last updated
- 25 Jul 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 Jul 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effects of 12-months of Denosumab on Bone Density, Quality and Strength in Prevalent Kidney Transplant Recipients
- ClinicalTrials.gov ID
- NCT03960554
- Acronym / sponsor ID
- ProliaKTx / AAAS3103
- Keywords
- Denosumab, Bone density, Kidney transplant, Prolia
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Study lost funding
- Enrolment
- 8 participants (actual)
- Lead sponsor
- Thomas Nickolas, MD MSUniversity, hospital or other
- Study start
- 16 Jan 2020 (actual)
- Primary completion
- 2 Dec 2021 (actual)
- Study completion
- 2 Dec 2021 (actual)
- First posted
- 23 May 2019 (actual)
- Results
- Posted 25 Jul 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Active drug | Active comparator | Drug: Denosumab Inj 60 mg/mlDenosumab 60 mg subcutaneous injection every 6 months for 12 months (i.e., 2 injections) |
| Placebo | Placebo comparator | Other: PlaceboPlacebo subcutaneous injection every 6 months for 12 months (i.e., 2 injections) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- 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:
Key exclusion criteria (18 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Denosumab Inj 60 mg/mlAlso: ProliaTreatment will be administered by study personnel as a subcutaneous injection every 6-months for one year. | Drug | Active drug |
| PlaceboPlacebo will be administered by study personnel as a subcutaneous injection every 6-months for one year. | Other | Placebo |
Primary outcome
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.
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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Jul 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Thomas Nickolas, MD, MS principal investigator
Columbia University
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Denosumab Inj 60 mg/ml in people with Osteoporosis and Renal Osteodystrophy, run by Thomas Nickolas, MD MS at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 16 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 25 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 25 Jul 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Bone Mineral Density (BMD) Measured by Dual Energy X-ray Absorptiometry (DXA) (time frame: 12 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Jul 2024.