Ignite Creation Date:
2024-05-06 @ 12:22 AM
Last Modification Date:
2024-10-26 @ 10:48 AM
Study NCT ID:
NCT01558115
Status:
TERMINATED
Last Update Posted:
2022-11-02
First Post:
2012-03-16
Brief Title:
Denosumab in Primary Hyperparathyroidism
Sponsor:
Columbia University
Organization:
Columbia University
Study Overview
Official Title:
Denosumab in Primary Hyperparathyroidism
Status:
TERMINATED
Status Verified Date:
2022-10
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Poor enrollment
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief 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 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
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
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 Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 20090741 | OTHER | Amgen | httpsreporternihgovquickSearchR01DK032333 |
| R01DK032333 | NIH | None | None |