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Burosumab and 1-25 (OH) Vitamin D on Human Osteoblasts (HYPO-BLASTE)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04159675
Recruitment Status : Not yet recruiting
First Posted : November 12, 2019
Last Update Posted : January 22, 2020
Sponsor:
Information provided by (Responsible Party):
Hospices Civils de Lyon

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.


Condition or disease Intervention/treatment
Craniosynostoses Biological: osteoblast biology study

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Study Type : Observational
Estimated Enrollment : 20 participants
Observational Model: Case-Control
Time Perspective: Prospective
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)
Estimated Study Start Date : February 1, 2020
Estimated Primary Completion Date : February 2, 2022
Estimated Study Completion Date : February 2, 2022


Group/Cohort Intervention/treatment
control patients
Patients with idiopathic craniosynostosis
Biological: osteoblast biology study
Describe the in-vitro action of burosumab and vitamin D on human osteoblastogenesis from osteoblasts from patients with craniosynostosis due to HR

HR patients
Patients with craniosynostosis due to HR
Biological: osteoblast biology study
Describe the in-vitro action of burosumab and vitamin D on human osteoblastogenesis from osteoblasts from patients with craniosynostosis due to HR




Primary Outcome Measures :
  1. Number of osteoblastic cells obtained at the end of differentiation [ Time Frame: Day 0 ]
    The analysis of osteoblastic differentiation obtained from the bone cells from patients with burosumab and/or 1-25 (OH) vitamin D (HR patients vs idiopathic craniosynostosis)


Biospecimen Retention:   Samples Without DNA
pieces of bone skull (considered as biological waste) during surgery


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Ages Eligible for Study:   4 Months to 18 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
patients with craniosynostosis, idiopathic (control patients) or due to HR
Criteria

Inclusion Criteria:

  • Children from 4 months-old to 18 years-old
  • Patients requiring craniosynostosis surgery followed by reference centers for rare diseases of calcium and phosphate metabolism / craniofacial malformations
  • Patients and parent / holder of parental authority who have been informed of the study and do not object to participate

Exclusion Criteria:

  • Patient being treated with oral corticosteroid or having received more than 3 months of corticosteroid treatment before surgery.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04159675


Contacts
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Contact: Federico DI ROCCO, MD federico.dirocco@chu-lyon.fr
Contact: Justine BACCHETTA, MD justine.bacchetta@chu-lyon.fr

Locations
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France
Centre de référence des craniosténoses et malformations cranio-faciales Service de neurochirurgie Pédiatrique
Bron, France, 69500
Contact: Federico DI ROCCO, MD       federico.dirocco@chu-lyon.fr   
Contact: Justine BACCHETTA, MD       justine.bacchetta@chu-lyon.fr   
Principal Investigator: Federico DI ROCCO, MD         
Sub-Investigator: Justine BACCHETTA, MD         
Sub-Investigator: Aurélia BERTHOLET-THOMAS, MD         
Sponsors and Collaborators
Hospices Civils de Lyon
Investigators
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Principal Investigator: Federico DI ROCCO, MD Hospices Civils de Lyon Centre de référence des craniosténoses et malformations cranio-faciales Service de neurochirurgie Pédiatrique
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Responsible Party: Hospices Civils de Lyon
ClinicalTrials.gov Identifier: NCT04159675    
Other Study ID Numbers: 69HCL19_0773
2019-A02762-55 ( Other Identifier: ID-RCB )
First Posted: November 12, 2019    Key Record Dates
Last Update Posted: January 22, 2020
Last Verified: January 2020

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Craniosynostoses
Synostosis
Dysostoses
Bone Diseases, Developmental
Bone Diseases
Musculoskeletal Diseases
Craniofacial Abnormalities
Musculoskeletal Abnormalities
Congenital Abnormalities