- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04671719
Determination of Circulating Autotaxin in Patients With GNAS or PTH Abnormalities (GNAS-AUTAX)
Autotaxin in Patients With GNAS/PTH Abnormalities
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.
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Actual)
Contacts and Locations
Study Contact
- Name: BACCHETTA Justine, Pr
- Phone Number: +33 4 27 85 61 30
- Email: justine.bacchetta@chu-lyon.fr
Study Contact Backup
- Name: FLAMMIER Sacha, PhD
- Phone Number: +33 4 72 68 13 49
- Email: sacha.flammier@chu-lyon.fr
Study Locations
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-
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Bron, France, 69500
- Centre de compétence des maladies rares de l'insulino-sécrétion et de l'insulino-sensibilité
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Lyon, France, 69003
- Centre de référence Dysplasie Fibreuse des os Service rhumatologie et pathologie osseuse Hôpital Edouard Herriot, Lyon
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Paris, France, 94270
- 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
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Sampling Method
Study Population
Patients from 10 to 18 years old :
- Fibrous dysplasia / McCune-Albright syndrome,
- hypoparathyroïdism,
- hyperparathyroïdism,
- 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).
Description
Inclusion Criteria:
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
Exclusion Criteria:
- 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
Study Plan
How is the study designed?
Design Details
- Observational Models: Case-Control
- Time Perspectives: Prospective
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Concentration of circulating autotaxin
Time Frame: At inclusion
|
Concentration of circulating autotaxin measured in patient serum by ELISA assay
|
At inclusion
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: BACCHETTA Justine, Pr, Centre de Référence des Maladies Rares du Calcium et du Phosphate
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Metabolic Diseases
- Endocrine System Diseases
- Genetic Diseases, Inborn
- Musculoskeletal Diseases
- Parathyroid Diseases
- Bone Diseases
- Metabolism, Inborn Errors
- Bone Diseases, Metabolic
- Calcium Metabolism Disorders
- Bone Diseases, Developmental
- Metal Metabolism, Inborn Errors
- Osteochondrodysplasias
- Hyperparathyroidism
- Hypoparathyroidism
- Fibrous Dysplasia of Bone
- Pseudohypoparathyroidism
- Pseudopseudohypoparathyroidism
- Fibrous Dysplasia, Polyostotic
Other Study ID Numbers
- 69HCL20_0628
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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