Fibrous DysplasiaGNAS-AUTAXNCT04671719
Determination of Circulating Autotaxin in Patients With GNAS or PTH Abnormalities
An observational study of Fibrous Dysplasia and Albright Syndrome, run by Hospices Civils de Lyon at 3 sites in France.
Trial 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. Read more about this study
- Who is it for?
- Ages 10 years and older
- Conditions the study is for
- Fibrous Dysplasia, Albright Syndrome, Adult Children
- What is being tested?
- blood sample
- How many people
- 33 participants
- Where
- 3 sitesFrance
- Study dates
- 10 Mar 2021to 11 Jan 2023
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 10 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
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).
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
3 sites in 1 country.
France3 sites
Centre de compétence des maladies rares de l'insulino-sécrétion et de l'insulino-sensibilité
Bron, 69500
Centre de référence Dysplasie Fibreuse des os Service rhumatologie et pathologie osseuse Hôpital Edouard Herriot, Lyon
Lyon, 69003
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
About this study
Official title: 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.
Read more
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
- Being tested
- blood sample
- Keywords
- Fibrous dysplasia / McCune-Albright syndrome, hypoparathyroidism, hyperparathyroidism, iPPSD, autotaxin, GNAS, PTH
- Medical subject headings
- Fibrous Dysplasia of Bone, Fibrous Dysplasia, Polyostotic, Hypoparathyroidism, Hyperparathyroidism, Pseudohypoparathyroidism
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
blood sampleBiological
blood sample for circulating autotaxin measurement (5ml).
What is being measured
The primary outcome is the main question the study is designed to answer.
Concentration of circulating autotaxin
Concentration of circulating autotaxin measured in patient serum by ELISA assay
Measured: At inclusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Dec 2020
- Study start10 Mar 2021
- Primary completion11 Jan 2023
- Study completion11 Jan 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Fibrous DysplasiaStudies of the same condition, open and under way.
- More trials run by Hospices Civils de LyonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 33 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hospices Civils de Lyon
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- BACCHETTA Justine, Pr, Principal investigator, Centre de Référence des Maladies Rares du Calcium et du Phosphate
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04671719
- Sponsor's protocol ID
- 69HCL20_0628
- Acronym
- GNAS-AUTAX
- Status last verified
- Feb 2023
- First submitted
- 11 Dec 2020
- Last updated
- 24 Mar 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 24 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Autotaxin in Patients With GNAS/PTH Abnormalities
- ClinicalTrials.gov ID
- NCT04671719
- Acronym / sponsor ID
- GNAS-AUTAX / 69HCL20_0628
- Conditions
- Fibrous Dysplasia, Albright Syndrome, Adult Children, Hypoparathyroidism, Hyperparathyroidism, Pseudo Hypoparathyroidism
- Keywords
- Fibrous dysplasia / McCune-Albright syndrome, hypoparathyroidism, hyperparathyroidism, iPPSD, autotaxin, GNAS, PTH
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 33 participants (actual)
- Lead sponsor
- Hospices Civils de LyonUniversity, hospital or other
- Study start
- 10 Mar 2021 (actual)
- Primary completion
- 11 Jan 2023 (actual)
- Study completion
- 11 Jan 2023 (actual)
- First posted
- 17 Dec 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Observational model
- Case-control
- Time perspective
- Prospective
Who may qualify
- Ages
- 10 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- 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).
Key inclusion criteria (8 listed)
- 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
- Patients > 18 years old
- Patients with Fibrous dysplasia / McCune-Albright syndrome, followed in reference center for constitutional bone diseases at hôpital Edouard Herriot (Lyon)
Key exclusion criteria (6 listed)
- Children < 8 kg
- Patient with hepatic disease
- Patients under tutorship or curatorship
- Pregnant and / or breastfeeding woman
- Patient deprived of liberty
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| blood sampleblood sample for circulating autotaxin measurement (5ml). | Biological | – |
Primary outcome
Concentration of circulating autotaxin
Time frame: At inclusion
Concentration of circulating autotaxin measured in patient serum by ELISA assay
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Mar 2023.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
BACCHETTA Justine, Pr principal investigator
Centre de Référence des Maladies Rares du Calcium et du Phosphate
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Fibrous Dysplasia and Albright Syndrome, run by Hospices Civils de Lyon at 3 sites in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Concentration of circulating autotaxin (time frame: At inclusion). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Mar 2023.