Ignite Creation Date:
2024-05-06 @ 1:54 PM
Last Modification Date:
2024-10-26 @ 1:22 PM
Study NCT ID:
NCT04159675
Status:
RECRUITING
Last Update Posted:
2024-03-15
First Post:
2019-11-07
Brief Title:
Burosumab and 1-25 OH Vitamin D on Human Osteoblasts
Sponsor:
Hospices Civils de Lyon
Organization:
Hospices Civils de Lyon
Study Overview
Official Title:
Effect of Burosumab and 1-25 OH Vitamin D on Human Osteoblasts From Patients Requiring Craniosynostosis Surgery for Idiopathic Reason or Due to Hypophosphatemic Rickets HR
Status:
RECRUITING
Status Verified Date:
2024-03
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
HYPO-BLASTES
Brief Summary:
FGF23 is the cornerstone of phosphate calcium vitamin D metabolism it is synthesized mainly by osteocytes and acts as a phosphaturizing agent inhibitor of dihydroxyvitamin D and inhibitor of synthesis and secretion of PTH in most tissues
The specific role of FGF23 on bone has yet to be demonstrated In osteoblasts overexpression of FGF23 in vitro suppresses not only osteoblastic differentiation but also the synthesis of the mineralized matrix independently of its systemic action on phosphate metabolism In osteoblasts FGF23 also regulates the secretion of osteopontin by directly suppressing transcription of alkaline phosphatase
In some diseases such as hypophosphatemic rickets HR the direct role of FGF23 on bone has not yet been studied to our knowledge whereas these genetic hypophosphatemias are secondary to overexpression of FGF23 whether an activating mutation of FGF23 or inhibitory mutations of its inhibitors DMP1 and PHEX However patients with X-linked hypophosphatemic rickets XLH have higher circulating FGF23 levels than healthy controls and these levels are higher in treated patients
Management of XLH consists primarily of correcting the native vitamin D defect by prescribing active vitamin D analogs as well as phosphate supplementation to improve bone mineralization and decrease dental complications growth and bone deformities Recently a new therapeutic option has been developed for XLH burosumab a human monoclonal antibody that binds and inhibits FGF23 activity The use of burosumab is currently authorized in France in some pediatric patients with severe forms of XLH
Independently of the indirect bone effects of phosphate correction and vitamin D levels the direct role of burosumab on bone cells has never been studied The objective of this project is to study the osteoblastic biology of patients with RH compared to control patients and to evaluate the direct impact of the treatments used in this pathology on human osteoblasts
The specific role of FGF23 on bone has yet to be demonstrated In osteoblasts overexpression of FGF23 in vitro suppresses not only osteoblastic differentiation but also the synthesis of the mineralized matrix independently of its systemic action on phosphate metabolism In osteoblasts FGF23 also regulates the secretion of osteopontin by directly suppressing transcription of alkaline phosphatase
In some diseases such as hypophosphatemic rickets HR the direct role of FGF23 on bone has not yet been studied to our knowledge whereas these genetic hypophosphatemias are secondary to overexpression of FGF23 whether an activating mutation of FGF23 or inhibitory mutations of its inhibitors DMP1 and PHEX However patients with X-linked hypophosphatemic rickets XLH have higher circulating FGF23 levels than healthy controls and these levels are higher in treated patients
Management of XLH consists primarily of correcting the native vitamin D defect by prescribing active vitamin D analogs as well as phosphate supplementation to improve bone mineralization and decrease dental complications growth and bone deformities Recently a new therapeutic option has been developed for XLH burosumab a human monoclonal antibody that binds and inhibits FGF23 activity The use of burosumab is currently authorized in France in some pediatric patients with severe forms of XLH
Independently of the indirect bone effects of phosphate correction and vitamin D levels the direct role of burosumab on bone cells has never been studied The objective of this project is to study the osteoblastic biology of patients with RH compared to control patients and to evaluate the direct impact of the treatments used in this pathology on human osteoblasts
Detailed Description:
None
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 2019-A02762-55 | OTHER | ID-RCB | None |