Burosumab and 1-25 (OH) Vitamin D on Human Osteoclasts

NCT ID: NCT04184661

Last Updated: 2022-10-06

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

52 participants

Study Classification

OBSERVATIONAL

Study Start Date

2021-01-20

Study Completion Date

2021-10-27

Brief Summary

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Fibroblast growth factor 23 (FGF23) is the cornerstone of phosphate / calcium / vitamin D metabolism: it is synthesized mainly by osteocytes and acts as a Phosphating agent, inhibitor of dihydroxyvitamin D, and inhibitor of synthesis and secretion of Parathyroid hormone (PTH) in most tissues.

The specific role of FGF23 on bone has yet to be demonstrated. 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 (Dentin matrix acidic phosphoprotein 1 (DMP1) and Phosphate-regulating neutral endopeptidase, X-linked (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 osteoclastic biology of patients with HR compared to control patients, and to evaluate the direct impact of the treatments used in this pathology on human osteoclasts.

Detailed Description

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Conditions

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Hypophosphatemic Rickets

Study Design

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Observational Model Type

CASE_CONTROL

Study Time Perspective

PROSPECTIVE

Study Groups

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hypophosphatemic rickets patients

30 hypophosphatemic rickets patients older than 2 years will be included in this study

blood sample

Intervention Type OTHER

25 mL blood sample will be collected on citrate tubes for osteoclastic analysis.

controls patients

10 controls patients from pediatric nephrology unit without hypophosphatemic rickets, older than 2 years will be included in this study

blood sample

Intervention Type OTHER

25 mL blood sample will be collected on citrate tubes for osteoclastic analysis.

Interventions

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blood sample

25 mL blood sample will be collected on citrate tubes for osteoclastic analysis.

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

* children from 2 yars-old to 18 years old and adults
* patients with HR followed in the center of calcium and phosphorus metabolism rare diseases in Lyon-
* Patients and parent / holder of parental authority who have been informed of the study and do not object to participate


* children from 2 years-old to 18 years old and adults
* patients with normal renal function (Schwartz glomerular filtration rate (GFR) \>90 ml/min/1.73m²)
* 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.
* Patients under tutorship or curatorship
* Pregnant and / or breastfeeding woman
* Patient deprived of liberty

Controls patients:


* Patient being treated with oral corticosteroid or having received more than 3 months of corticosteroid treatment before surgery.
* Patients under tutorship or curatorship
* Pregnant and / or breastfeeding woman
* Patient deprived of liberty
* Patient treated with immunosuppressive drugs
* Patient with inflammatory disease
Minimum Eligible Age

2 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Hospices Civils de Lyon

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Hôpital Femme mère enfant

Bron, , France

Site Status

Hôpital Edouard Herriot

Lyon, , France

Site Status

Hôpital Bicêtre Paris Saclay

Paris, , France

Site Status

Countries

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France

Other Identifiers

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2019-A02914-53

Identifier Type: OTHER

Identifier Source: secondary_id

69HCL19_0725

Identifier Type: -

Identifier Source: org_study_id

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