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

NCT04184661 | Completed

• 2 other identifiers: 69HCL19_07252019-A02914-53
• Study Type: observational
• Target: 52
• Locations: 1 country
• Sites: 3

Brief Summary

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.

Conditions

Hypophosphatemic Rickets

Outcome Measures

Primary Outcomes (1)

• number of osteoclastic cells obtained after at the end of differentiation

  The analysis of osteoclastic differentiation will be obtained from the bone cells from patients with burosumab and/or 1-25 (OH) vitamin D

  1 day

Study Arms (2)

hypophosphatemic rickets patients

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

Other: blood sample

controls patients

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

Other: blood sample

Interventions

blood sample OTHER

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

controls patients; hypophosphatemic rickets patients

Eligibility Criteria

• Age: 2 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

patients with hypophosphatemic rickets and controls patients without hypophosphatemic rickets

You may qualify if:

• 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

You may not qualify if:

• 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:
• 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
• 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

Sponsors & Collaborators

• Hospices Civils de Lyon: lead

Study Sites (3)

Hôpital Femme mère enfant

Bron, 69677, France

Location

Hôpital Edouard Herriot

Lyon, France

Location

Hôpital Bicêtre Paris Saclay

Paris, France

Location

Biospecimen

Retention: SAMPLES WITHOUT DNA

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

MeSH Terms

Conditions

Rickets, Hypophosphatemic

Interventions

Blood Specimen Collection

Condition Hierarchy (Ancestors)

Rickets; Bone Diseases, Metabolic; Bone Diseases; Musculoskeletal Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases; Calcium Metabolism Disorders; Hypophosphatemia; Phosphorus Metabolism Disorders; Vitamin D Deficiency; Avitaminosis; Deficiency Diseases; Malnutrition; Nutrition Disorders

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 28, 2019
• First Posted: December 3, 2019
• Study Start: January 20, 2021
• Primary Completion: October 27, 2021
• Study Completion: October 27, 2021
• Last Updated: October 6, 2022

Record last verified: 2022-10

Locations

FR (3)