Primary HyperparathyroidismPhase 4NCT01558115
Denosumab in Primary Hyperparathyroidism
A Phase 4 study testing Denosumab in people with Primary Hyperparathyroidism, run by Columbia University at 1 site in United States.
Trial summary
Primary hyperparathyroidism (PHPT), a disease characterized by excess parathyroid hormone (PTH) and high blood calcium, is one of the most common endocrine disorders. PHPT is seen most often in postmenopausal women. Read more about this study
- Who is it for?
- Ages 40 years and older, women only
- Conditions the study is for
- Primary Hyperparathyroidism
- What is being tested?
- Denosumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 8 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2012to Oct 2014
- Phase
- Phase 4
- 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 40 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Confirmed hypercalcemic PHPT in postmenopausal women with serum calcium >10.2 mg/dL and < 12.0 mg/dL (nl: 8.6-10.2)
- T-score between -1.5 and -2.5 at any site. If the T-score is <-2.5, patients become candidates for parathyroid surgery. They will be enrolled only if they refuse the parathyroid surgery
Who cannot join
- 25-hydroxyvitamin D level < 20 ng/ml
- Previous use of the bisphosphonate zoledronic acid (ever), alendronate or risedronate (within 12 months) or ibandronate (within 6 months)
- Current use of PTH, glucocorticoids, SERMS, estrogen (other than vaginal), calcitonin or pharmacological amounts of calcitriol Current or previous use of cinacalcet (within 6 months)
- Hyperthyroidism
- Rheumatoid arthritis or any other inflammatory joint disease
- Paget's disease of bone
Show all 14Show fewer
- Malabsorption
- T-score <-3.5 at any site
- Signs of symptomatic PHPT (e.g, kidney stones within the past 5 years; fragility fracture within the past 2 years)
- Physical or mental handicapping condition that precludes ability to complete the protocol and/or provide informed consent.
- Subjects on Antiviral HIV therapy or subjects with compromised immune systems
- Premenopausal women or men
- Stage 5 Chronic Kidney Disease (CKD) or anyone on dialysis
- Creatinine clearance < 30 cc/min unless the patient is not a candidate for surgery or if the patient refuses surgery
Trial locations and contacts
1 site in 1 country.
United States1 site
Columbia University Medical Center
New York, New York, 10032
About this study
Primary hyperparathyroidism (PHPT), a disease characterized by excess parathyroid hormone (PTH) and high blood calcium, is one of the most common endocrine disorders. PHPT is seen most often in postmenopausal women. Many patients with PHPT have low bone mineral density (BMD) when bone mass is measured by dual energy x-ray absorptiometry (DXA), primarily at the forearm. There is currently no effective medical therapy which increases bone density at the forearm in patients with PHPT.
PTH both builds and breaks down bone, and the pathways by which PTH mediates these actions are beginning to be identified. Prior research suggests that RANKL, a molecule important in bone metabolism, responds to PTH, and that if the RANKL is inactivated, PTH is shifted towards building bone. The investigators will study the effect of Denosumab, a therapeutic agent that binds to and inactivates RANKL, in 28 postmenopausal women with PHPT. Our hypothesis is that Denosumab will increase bone mineral density in primary hyperparathyroidism.
The study will last two years, and subjects will be randomly assigned to receive either placebo or Denosumab for the first year of the study. In the second year, all subjects will receive Denosumab. Denosumab (60 mg) or placebo will be given every 6 months by an injection just under the skin. Study procedures performed will include bone mineral density tests by DXA, high-resolution peripheral quantitative computed tomography (HR-pQCT) scans, and assessments of biochemical markers of calcium metabolism and bone turnover using both blood and urine samples of subjects with PHPT.
Read the detailed description
PTH has both catabolic and anabolic properties, and under normal circumstances, PTH in PHPT is catabolic for bone at the cortical skeleton. Recently, evidence for a direct role of PTH on RANKL expression and osteoclastogenesis in vivo was obtained using mice lacking a distant transcriptional enhancer of the RANKL gene that confers responsiveness to PTH. These observations, supported by additional cross-sectional studies in human subjects make a compelling argument that the catabolic actions of PTH are mediated by RANKL-mediated bone resorption.
The investigators now propose a proof of concept study to test the hypothesis that in PHPT, inhibition of the RANK-L pathway will unmask the anabolic potential of PTH. A therapeutic agent that redirects the actions of PTH in PHPT from one that is primarily catabolic to an anabolic one would fulfill this proof of concept. The investigators hypothesize that Denosumab, a human Immunoglobulin G (IgG) antibody that binds to and inactivates RANKL, will convert skeletal actions of PTH from catabolic to anabolic in primary hyperparathyroidism.
- Conditions
- Primary Hyperparathyroidism
- Being tested
- Denosumab, Placebo
- Keywords
- Columbia University, Primary hyperparathyroidism, Low bone density, Denosumab, Prolia
- Medical subject headings
- Hyperparathyroidism, Primary, Bone Diseases, Metabolic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DenosumabDrug
Also called Prolia, Xgeva
The dose of denosumab is 60 mg every 6 months by subcutaneous injection.
The 52 subjects will be randomly allocated (2:1) into treatment and placebo arms with the placebo group receiving a subcutaneous injection of vehicle in year 1. In year 2, those who were allocated to the study drug in year 1 will continue in year 2. Those who were allocated to placebo in year 1 will be crossed over to study drug in year 2.
Group # 1: Receive active drug for year 1 and year 2 of the study
Group #2: Receive placebo for year 1 and active drug for year 2 of the study
PlaceboOther
The dose of denosumab is 60 mg every 6 months by subcutaneous injection. The placebo group will receive vehicle injections at the same time interval.
The 52 subjects will be randomly allocated (2:1) into treatment and placebo arms with the placebo group receiving a subcutaneous injection of vehicle in year 1. In year 2, those who were allocated to the study drug in year 1 will continue in year 2. Those who were allocated to placebo in year 1 will be crossed over to study drug in year 2.
Group # 1: Receive active drug for year 1 and year 2 of the study
Group #2: Receive placebo for year 1 and active drug for year 2 of the study
| Study group | Role | What they receive |
|---|---|---|
| Denosumab - Group #1 | Experimental | Receive active drug for year 1 and year 2 of the study Receives: Drug: Denosumab |
| Placebo - Group #2 | Placebo comparator | Receive placebo for year 1 and active drug for year 2 of the study Receives: Drug: Denosumab; Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Bone Mineral Density (BMD) at the Lumbar Spine
Percent change from baseline in BMD at the lumbar spine, as measured by Dual-emission X-ray absorptiometry (DXA) scan at 12 months
Measured: Baseline and 12 months
Secondary outcomes (2)
Change in Bone Mineral Density (BMD) at the Distal 1/3 Radius
Percent change from baseline in BMD at the distal 1/3 radius, as measured by Dual-emission X-ray absorptiometry (DXA) scan at 12 months
Measured: 12 months
Change in Bone Mineral Density (BMD) at the Hip
Percent change from baseline in BMD at the hip, as measured by Dual-emission X-ray absorptiometry (DXA) scan at 12 months
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 posted20 Mar 2012 (estimated)
- Study startJan 2012
- Primary completionOct 2014
- Study completionOct 2014
Why it stopped: Poor enrollment
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 Primary HyperparathyroidismStudies of the same condition, open and under way.
- More trials run by Columbia UniversityThe sponsor's other registered studies.
- 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 4
- 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
- Columbia University
- Sponsor type
- University, hospital or other
- Collaborators
- National Institutes of Health (NIH), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), Amgen
- Responsible party
- Sponsor
- Investigators
- John P Bilezikian, MD, Principal investigator, Columbia University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01558115
- Sponsor's protocol ID
- AAAF2568
- Other IDs
- R01DK032333, 20090741
- Status last verified
- Oct 2022
- First submitted
- 16 Mar 2012
- Last updated
- 2 Nov 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Nov 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Denosumab in Primary Hyperparathyroidism
- ClinicalTrials.gov ID
- NCT01558115
- Acronym / sponsor ID
- AAAF2568
- Conditions
- Primary Hyperparathyroidism
- Keywords
- Columbia University, Primary hyperparathyroidism, Low bone density, Denosumab, Prolia
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Poor enrollment
- Enrolment
- 8 participants (actual)
- Lead sponsor
- Columbia UniversityUniversity, hospital or other
- Collaborators
- National Institutes of Health (NIH), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), Amgen
- Study start
- Jan 2012 (actual)
- Primary completion
- Oct 2014 (actual)
- Study completion
- Oct 2014 (actual)
- First posted
- 20 Mar 2012 (estimated)
- Results
- Posted 2 Nov 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Primary hyperparathyroidism (PHPT), a disease characterized by excess parathyroid hormone (PTH) and high blood calcium, is one of the most common endocrine disorders. PHPT is seen most often in postmenopausal women. Many patients with PHPT have low bone mineral density (BMD) when bone mass is measured by dual energy x-ray absorptiometry (DXA), primarily at the forearm. There is currently no effective medical therapy which increases bone density at the forearm in patients with PHPT.
PTH both builds and breaks down bone, and the pathways by which PTH mediates these actions are beginning to be identified. Prior research suggests that RANKL, a molecule important in bone metabolism, responds to PTH, and that if the RANKL is inactivated, PTH is shifted towards building bone. The investigators will study the effect of Denosumab, a therapeutic agent that binds to and inactivates RANKL, in 28 postmenopausal women with PHPT. Our hypothesis is that Denosumab will increase bone mineral density in primary hyperparathyroidism.
The study will last two years, and subjects will be randomly assigned to receive either placebo or Denosumab for the first year of the study. In the second year, all subjects will receive Denosumab. Denosumab (60 mg) or placebo will be given every 6 months by an injection just under the skin. Study procedures performed will include bone mineral density tests by DXA, high-resolution peripheral quantitative computed tomography (HR-pQCT) scans, and assessments of biochemical markers of calcium metabolism and bone turnover using both blood and urine samples of subjects with PHPT.
Detailed description
PTH has both catabolic and anabolic properties, and under normal circumstances, PTH in PHPT is catabolic for bone at the cortical skeleton. Recently, evidence for a direct role of PTH on RANKL expression and osteoclastogenesis in vivo was obtained using mice lacking a distant transcriptional enhancer of the RANKL gene that confers responsiveness to PTH. These observations, supported by additional cross-sectional studies in human subjects make a compelling argument that the catabolic actions of PTH are mediated by RANKL-mediated bone resorption.
The investigators now propose a proof of concept study to test the hypothesis that in PHPT, inhibition of the RANK-L pathway will unmask the anabolic potential of PTH. A therapeutic agent that redirects the actions of PTH in PHPT from one that is primarily catabolic to an anabolic one would fulfill this proof of concept. The investigators hypothesize that Denosumab, a human Immunoglobulin G (IgG) antibody that binds to and inactivates RANKL, will convert skeletal actions of PTH from catabolic to anabolic in primary hyperparathyroidism.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Denosumab - Group #1 | Experimental | Drug: DenosumabReceive active drug for year 1 and year 2 of the study |
| Placebo - Group #2 | Placebo comparator | Drug: Denosumab, Other: PlaceboReceive placebo for year 1 and active drug for year 2 of the study |
Who may qualify
- Ages
- 40 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Confirmed hypercalcemic PHPT in postmenopausal women with serum calcium >10.2 mg/dL and < 12.0 mg/dL (nl: 8.6-10.2)
- T-score between -1.5 and -2.5 at any site. If the T-score is <-2.5, patients become candidates for parathyroid surgery. They will be enrolled only if they refuse the parathyroid surgery
Key exclusion criteria (14 listed)
- 25-hydroxyvitamin D level < 20 ng/ml
- Previous use of the bisphosphonate zoledronic acid (ever), alendronate or risedronate (within 12 months) or ibandronate (within 6 months)
- Current use of PTH, glucocorticoids, SERMS, estrogen (other than vaginal), calcitonin or pharmacological amounts of calcitriol Current or previous use of cinacalcet (within 6 months)
- Hyperthyroidism
- Rheumatoid arthritis or any other inflammatory joint disease
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 |
|---|---|---|
| DenosumabAlso: Prolia, XgevaThe dose of denosumab is 60 mg every 6 months by subcutaneous injection. The 52 subjects will be randomly allocated (2:1) into treatment and placebo arms with the placebo group receiving a subcutaneous injection of vehicle in year 1. In year 2, those who were allocated to the study drug in year 1 will continue in year 2. Those who were allocated to placebo in year 1 will be crossed over to study drug in year 2. Group # 1: Receive active drug for year 1 and year 2 of the study Group #2: Receive placebo for year 1 and active drug for year 2 of the study | Drug | Denosumab - Group #1, Placebo - Group #2 |
| PlaceboThe dose of denosumab is 60 mg every 6 months by subcutaneous injection. The placebo group will receive vehicle injections at the same time interval. The 52 subjects will be randomly allocated (2:1) into treatment and placebo arms with the placebo group receiving a subcutaneous injection of vehicle in year 1. In year 2, those who were allocated to the study drug in year 1 will continue in year 2. Those who were allocated to placebo in year 1 will be crossed over to study drug in year 2. Group # 1: Receive active drug for year 1 and year 2 of the study Group #2: Receive placebo for year 1 and active drug for year 2 of the study | Other | Placebo - Group #2 |
Primary outcome
Change in Bone Mineral Density (BMD) at the Lumbar Spine
Time frame: Baseline and 12 months
Percent change from baseline in BMD at the lumbar spine, as measured by Dual-emission X-ray absorptiometry (DXA) scan at 12 months
2 secondary outcomes
Change in Bone Mineral Density (BMD) at the Distal 1/3 Radius
Time frame: 12 months
Change in Bone Mineral Density (BMD) at the Hip
Time frame: 12 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Nov 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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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.
John P Bilezikian, MD principal investigator
Columbia University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Denosumab in people with Primary Hyperparathyroidism, run by Columbia University at 1 site 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 2 inclusion and 14 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 2 Nov 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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 2 Nov 2022). 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?
Change in Bone Mineral Density (BMD) at the Lumbar Spine (time frame: Baseline and 12 months). 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 2 Nov 2022.