Determination of Circulating Autotaxin in Patients With GNAS or PTH Abnormalities

NCT04671719 | Completed

• 1 other identifier: 69HCL20_0628
• Study Type: observational
• Target: 33
• Locations: 1 country
• Sites: 3

Brief Summary

PTH secretion defects (grouped under the name hypoparathyroidism) are due to abnormalities in the PTH gene, abnormalities in the development of the parathyroid glands which synthesize PTH or abnormalities of the calcium sening receptor whose role is to adapt PTH level to ambient calcium level. In contrast, primary hyperparathyroidism in children is also exceptional; expressed by hypercalcemia, with a renal and bon risk. Pseudo-hypoparathyroidism, now known under the term inactivating PTH / PTHrP Signaling Disorder or iPPSD, are rare pathologies characterized by resistance to the action of PTH sometimes associated with other symptoms, in particular chondrodysplasia. They are linked to a defect in the action of a factor in the signaling pathway of G protein-coupled receptors that activate the production of cyclic AMP (cAMP). IPPSDs are most often due to a molecular defect in the GNAS gene, subject to parental imprint. Fibrous dysplasia / McCune-Albright syndrome is a rare disease caused by somatic "gain-of-function" mutations in the GNAS gene located on chromosome 20q13 leading to activation of the protein Gαs and inappropriate production of intracellular cyclic adenosine monophosphate (cAMP). The clinical phenotype is determined by the location and extent of the tissues affected by this mutation. Autotaxin (ATX) is a protein secreted by different tissues including the liver, fatty tissue, and bone. Today, ATX is described as the major source of LPA in the bloodstream. LPA interacts with one of its receptors on the surface of the cell membrane. Depending on the receptor engaged, one or more Gα subunits (G12 / 13, GQ, Gi / o or Gs) will activate multiple cell signaling pathways. In bone, ATX is expressed by osteoclasts and osteoblasts. Recent laboratory data have shown that PTH stimulates ATX expression in osteoblasts in a dose-dependent manner. The objective of this study is to provide clinical proof of concept that the PTH / Gαs / ATX pathway is truly significant in physiology and pathology, by studying the full spectrum of PTH and GNAS pathologies. If this proof of concept is obtained, therapeutic applications will probably be possible in the long term.

Conditions

Fibrous Dysplasia; Albright Syndrome; Adult Children; Hypoparathyroidism; Hyperparathyroidism; Pseudo Hypoparathyroidism

Keywords

Fibrous dysplasia / McCune-Albright syndrome, hypoparathyroidism, hyperparathyroidism, iPPSD, autotaxin, GNAS, PTH

Outcome Measures

Primary Outcomes (1)

• Concentration of circulating autotaxin

  Concentration of circulating autotaxin measured in patient serum by ELISA assay

  At inclusion

Interventions

blood sample BIOLOGICAL

blood sample for circulating autotaxin measurement (5ml).

Eligibility Criteria

• Age: 10 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 from 10 to 18 years old : 1. Fibrous dysplasia / McCune-Albright syndrome, 2. hypoparathyroïdism, 3. hyperparathyroïdism, 4. iPPSD, from References Centers for rare diseases (Calcium and phosphate metabolism, constitutional bone diseases) at hôpital Femme Mère Enfant (Bron) and at hôpital Bicêtre Paris Saclay (Paris). Adults with Fibrous dysplasia / McCune-Albright syndrome from reference center for constitutional bone diseases at hôpital Edouard Herriot (Lyon).

You may qualify if:

• Pediatric patients :
• Children from 10 to 18 years old
• Patients with Fibrous dysplasia / McCune-Albright syndrome,hypoparathyroïdism, hyperparathyroïdism, or iPPSD, from References Centers for rare diseases (Calcium and phosphate metabolism, constitutional bone diseases) followed at hôpital Femme Mère Enfant (Bron) or at hôpital Bicêtre Paris Saclay (Paris).
• Patients and parent / holder of parental authority who have been informed of the study and do not object to participate
• Adults:
• Patients \> 18 years old
• Patients with Fibrous dysplasia / McCune-Albright syndrome, followed in reference center for constitutional bone diseases at hôpital Edouard Herriot (Lyon)
• Patients who have been informed of the study and do not object to participate

You may not qualify if:

• Children \< 8 kg
• Patient with hepatic disease
• Patients under tutorship or curatorship
• Pregnant and / or breastfeeding woman
• Patient deprived of liberty
• Patient in emergency situation who can not agree to participate

Sponsors & Collaborators

• Hospices Civils de Lyon: lead

Study Sites (3)

Centre de compétence des maladies rares de l'insulino-sécrétion et de l'insulino-sensibilité

Bron, 69500, France

Location

Centre de référence Dysplasie Fibreuse des os Service rhumatologie et pathologie osseuse Hôpital Edouard Herriot, Lyon

Lyon, 69003, France

Location

Centre de Référence des Maladies Rares du Métabolisme du Calcium et du Phosphate Service d'Endocrinologie et Diabète de l'Enfant Hôpital Bicêtre Paris Saclay

Paris, 94270, France

Location

Biospecimen

Retention: SAMPLES WITHOUT DNA

serum

MeSH Terms

Conditions

Fibrous Dysplasia of Bone; Fibrous Dysplasia, Polyostotic; Hypoparathyroidism; Hyperparathyroidism; Pseudohypoparathyroidism

Interventions

Blood Specimen Collection

Condition Hierarchy (Ancestors)

Osteochondrodysplasias; Bone Diseases, Developmental; Bone Diseases; Musculoskeletal Diseases; Parathyroid Diseases; Endocrine System Diseases; Bone Diseases, Metabolic; Metal Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolic Diseases; Nutritional and Metabolic Diseases; Calcium Metabolism Disorders

Intervention Hierarchy (Ancestors)

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

Study Officials

• BACCHETTA Justine, Pr

  Centre de Référence des Maladies Rares du Calcium et du Phosphate

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: December 11, 2020
• First Posted: December 17, 2020
• Study Start: March 10, 2021
• Primary Completion: January 11, 2023
• Study Completion: January 11, 2023
• Last Updated: March 24, 2023

Record last verified: 2023-02

Locations

FR (3)