PIK3CA-related Overgrowth SpectrumCOSYNCT05563831
National Evaluation of Patients With PIK3CA-Related Overgrowth Spectrum (PROS)
An observational study of PIK3CA-related Overgrowth Spectrum and CLOVES Syndrome, run by Institut National de la Santé Et de la Recherche Médicale, France at 1 site in France.
Trial summary
Overgrowth syndromes are rare genetic disorders defined by tissue hypertrophy that can be either localized or generalized, affecting both latitudinal and longitudinal growth. The genes involved in overgrowth syndromes are not well characterized but mostly concern the PIK3CA/AKT/mTOR pathway, a major actor of cell… Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- PIK3CA-related Overgrowth Spectrum, CLOVES Syndrome, Klippel Trenaunay Syndrome
- What is being tested?
- national registry
- How many people
- 28 participants
- Where
- 1 siteFrance
- Study dates
- 21 Feb 2023to 7 Jun 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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: All patients with overgrowth syndrome referred by their doctors or patients who have sent a consultation request to the Reference Center (https://hopital-necker.aphp.fr/contacts-cloves) will be enrolled.
Who may be able to join
- Affiliated to the French healthcare insurance system.
- Pediatric and adult patients
- Clinical diagnosis of overgrowth syndrome
- Written informed consent from adult patients and from both parents of pediatric patients.
Who cannot join
- Person subject to a judicial safeguard measure
- Inability to give informed consent
Trial locations and contacts
1 site in 1 country.
France1 site
Translational medicine and Targeted therapies unit, Hôpital Necker Enfants Malades
Paris, 75015
About this study
Official title: Evaluation Nationale Des Enfants et Adultes Avec Syndromes d'Hypercroissance Dysharmonieuse National Evaluation of Patients With PIK3CA-Related Overgrowth Spectrum (PROS)
Overgrowth syndromes are rare genetic disorders defined by tissue hypertrophy that can be either localized or generalized, affecting both latitudinal and longitudinal growth. The genes involved in overgrowth syndromes are not well characterized but mostly concern the PIK3CA/AKT/mTOR pathway, a major actor of cell growth and proliferation. The mutations are not inherited but occurs during embryogenesis leading to somatic mosaicism. Owing to the variability of the clinical presentation, their exact prevalence is yet unknown. In order to answer this question, the investigators team create here the first French national registry on overgrowth syndromes.
Read the detailed description
Overgrowth syndromes are rare genetic disorders defined by tissue hypertrophy that can be either localized or generalized, affecting both latitudinal and longitudinal growth. The genes involved in overgrowth syndromes are not well characterized but mostly concern the PIK3CA/AKT/mTOR pathway, a major actor of cell growth and proliferation. The mutations are not inherited but occurs during embryogenesis leading to somatic mosaicism. Owing to the variability of the clinical presentation, their exact prevalence is yet unknown. In order to answer this question, the investigators team create here the first French national registry on overgrowth syndromes.
- Conditions
- PIK3CA-related Overgrowth Spectrum, CLOVES Syndrome, Klippel Trenaunay Syndrome, Megalencephaly, MCAP, Macrodactyly
- Being tested
- national registry
- Keywords
- PIK3CA, Related Overgrowth Syndrome, PIK3CA/AKT/mTOR pathway, clinical diagnosis, Biobank, Patient Stratification
- Medical subject headings
- Congenital Lipomatous Overgrowth, Vascular Malformations, and Epidermal Nevi, Klippel-Trenaunay-Weber Syndrome, Megalencephaly, Megalodactyly, Vascular Malformations, Lymphatic Abnormalities, Hereditary Sensory and Autonomic Neuropathies
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
national registryOther
The investigators will collect demographic, clinical, biological and imaging characteristics of patients with PROS.
What is being measured
The primary outcome is the main question the study is designed to answer.
Description of patients with overgrowth syndromes
Clinical and molecular characterization of patients with overgrowth syndromes will be performed.
Measured: 5 years
Secondary outcomes (4)
Prevalence of overgrowth syndromes in France
An estimation of the prevalence of overgrowth syndromes in France will be done
Measured: 5 years
Biobanking of samples derived from patients with overgrowth syndromes
A biobank will be created with biological samples (plasma) collected for research and residual biological samples from patient cares (treatment/diagnosis)
Measured: 5 years
Description of patient cares: mumber of consultations and hospitalizations, number of treatment lines, grouping of patients by type of course (clusters)
An analysis of care trajectories will be performed. These data will be collected from health insurance databases for patients with overgrowth syndromes.
Measured: 5 years
Economic evaluation of cares for patients with overgrowth syndromes: cost of care, per period and cumulative.
SDNS data will be used to estimate care costs per year for patients with overgrowth syndrome.
Measured: 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Oct 2022
- Study start21 Feb 2023
- Primary completion7 Jun 2023
- Study completion7 Jun 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for PIK3CA-related Overgrowth SpectrumStudies of the same condition, open and under way.
- More trials run by Institut National de la Santé Et de la Recherche Médicale, FranceThe 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
- Cohort
- Time perspective
- Other
- Enrolment
- 28 participants (actual)
Sponsor and investigators
- Sponsor type
- Other government
- Responsible party
- Sponsor
- Investigators
- Guillaume Canaud, MD,PHD, Principal investigator, Institut National de la Santé Et de la Recherche Médicale, France
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05563831
- Sponsor's protocol ID
- C20-09
- Acronym
- COSY
- Status last verified
- Apr 2023
- First submitted
- 28 Jul 2022
- Last updated
- 23 Feb 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Canaud G, Hammill AM, Adams D, Vikkula M, Keppler-Noreuil KM. A review of mechanisms of disease across PIK3CA-related disorders with vascular manifestations. Orphanet J Rare Dis. 2021 Jul 8;16(1):306. doi: 10.1186/s13023-021-01929-8.
PubMed 34238334Morin G, Canaud G. Treatment strategies for mosaic overgrowth syndromes of the PI3K-AKT-mTOR pathway. Br Med Bull. 2021 Dec 16;140(1):36-49. doi: 10.1093/bmb/ldab023.
PubMed 34530449Delestre F, Venot Q, Bayard C, Fraissenon A, Ladraa S, Hoguin C, Chapelle C, Yamaguchi J, Cassaca R, Zerbib L, Magassa S, Morin G, Asnafi V, Villarese P, Kaltenbach S, Fraitag S, Duong JP, Broissand C, Boccara O, Soupre V, Bonnotte B, Chopinet C, Mirault T, Legendre C, Guibaud L, Canaud G. Alpelisib administration reduced lymphatic malformations in a mouse model and in patients. Sci Transl Med. 2021 Oct 6;13(614):eabg0809. doi: 10.1126/scitranslmed.abg0809. Epub 2021 Oct 6.
PubMed 34613809Morin G, Degrugillier-Chopinet C, Vincent M, Fraissenon A, Aubert H, Chapelle C, Hoguin C, Dubos F, Catteau B, Petit F, Mezel A, Domanski O, Herbreteau G, Alesandrini M, Boddaert N, Boutry N, Broissand C, Han TK, Branle F, Sarnacki S, Blanc T, Guibaud L, Canaud G. Treatment of two infants with PIK3CA-related overgrowth spectrum by alpelisib. J Exp Med. 2022 Mar 7;219(3):e20212148. doi: 10.1084/jem.20212148. Epub 2022 Jan 26.
PubMed 35080595Venot Q, Blanc T, Rabia SH, Berteloot L, Ladraa S, Duong JP, Blanc E, Johnson SC, Hoguin C, Boccara O, Sarnacki S, Boddaert N, Pannier S, Martinez F, Magassa S, Yamaguchi J, Knebelmann B, Merville P, Grenier N, Joly D, Cormier-Daire V, Michot C, Bole-Feysot C, Picard A, Soupre V, Lyonnet S, Sadoine J, Slimani L, Chaussain C, Laroche-Raynaud C, Guibaud L, Broissand C, Amiel J, Legendre C, Terzi F, Canaud G. Targeted therapy in patients with PIK3CA-related overgrowth syndrome. Nature. 2018 Jun;558(7711):540-546. doi: 10.1038/s41586-018-0217-9. Epub 2018 Jun 13.
PubMed 29899452Manning BD, Toker A. AKT/PKB Signaling: Navigating the Network. Cell. 2017 Apr 20;169(3):381-405. doi: 10.1016/j.cell.2017.04.001.
PubMed 28431241
Study at a glance
From the registry record, last updated by the sponsor on 23 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation Nationale Des Enfants et Adultes Avec Syndromes d'Hypercroissance Dysharmonieuse National Evaluation of Patients With PIK3CA-Related Overgrowth Spectrum (PROS)
- ClinicalTrials.gov ID
- NCT05563831
- Acronym / sponsor ID
- COSY / C20-09
- Conditions
- PIK3CA-related Overgrowth Spectrum, CLOVES Syndrome, Klippel Trenaunay Syndrome, Megalencephaly, MCAP, Macrodactyly
- Keywords
- PIK3CA, Related Overgrowth Syndrome, PIK3CA/AKT/mTOR pathway, clinical diagnosis, Biobank, Patient Stratification
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 28 participants (actual)
- Lead sponsor
- Institut National de la Santé Et de la Recherche Médicale, FranceOther government
- Study start
- 21 Feb 2023 (actual)
- Primary completion
- 7 Jun 2023 (actual)
- Study completion
- 7 Jun 2023 (actual)
- First posted
- 3 Oct 2022 (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.
Overgrowth syndromes are rare genetic disorders defined by tissue hypertrophy that can be either localized or generalized, affecting both latitudinal and longitudinal growth. The genes involved in overgrowth syndromes are not well characterized but mostly concern the PIK3CA/AKT/mTOR pathway, a major actor of cell growth and proliferation. The mutations are not inherited but occurs during embryogenesis leading to somatic mosaicism. Owing to the variability of the clinical presentation, their exact prevalence is yet unknown. In order to answer this question, the investigators team create here the first French national registry on overgrowth syndromes.
Detailed description
Overgrowth syndromes are rare genetic disorders defined by tissue hypertrophy that can be either localized or generalized, affecting both latitudinal and longitudinal growth. The genes involved in overgrowth syndromes are not well characterized but mostly concern the PIK3CA/AKT/mTOR pathway, a major actor of cell growth and proliferation. The mutations are not inherited but occurs during embryogenesis leading to somatic mosaicism. Owing to the variability of the clinical presentation, their exact prevalence is yet unknown. In order to answer this question, the investigators team create here the first French national registry on overgrowth syndromes.
Study design
- Observational model
- Cohort
- Time perspective
- Other
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- All patients with overgrowth syndrome referred by their doctors or patients who have sent a consultation request to the Reference Center (https://hopital-necker.aphp.fr/contacts-cloves) will be enrolled.
Key inclusion criteria (4 listed)
- Affiliated to the French healthcare insurance system.
- Pediatric and adult patients
- Clinical diagnosis of overgrowth syndrome
- Written informed consent from adult patients and from both parents of pediatric patients.
Key exclusion criteria (2 listed)
- Person subject to a judicial safeguard measure
- Inability to give informed consent
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 |
|---|---|---|
| national registryThe investigators will collect demographic, clinical, biological and imaging characteristics of patients with PROS. | Other | – |
Primary outcome
Description of patients with overgrowth syndromes
Time frame: 5 years
Clinical and molecular characterization of patients with overgrowth syndromes will be performed.
4 secondary outcomes
Prevalence of overgrowth syndromes in France
Time frame: 5 years
Biobanking of samples derived from patients with overgrowth syndromes
Time frame: 5 years
Description of patient cares: mumber of consultations and hospitalizations, number of treatment lines, grouping of patients by type of course (clusters)
Time frame: 5 years
Economic evaluation of cares for patients with overgrowth syndromes: cost of care, per period and cumulative.
Time frame: 5 years
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 23 Feb 2026.
- Background: PubMed 34238334Canaud G, Hammill AM, Adams D, Vikkula M, Keppler-Noreuil KM. A review of mechanisms of disease across PIK3CA-related disorders with vascular manifestations. Orphanet J Rare Dis. 2021 Jul 8;16(1):306. doi: 10.1186/s13023-021-01929-8.
- Background: PubMed 34530449Morin G, Canaud G. Treatment strategies for mosaic overgrowth syndromes of the PI3K-AKT-mTOR pathway. Br Med Bull. 2021 Dec 16;140(1):36-49. doi: 10.1093/bmb/ldab023.
- Background: PubMed 34613809Delestre F, Venot Q, Bayard C, Fraissenon A, Ladraa S, Hoguin C, Chapelle C, Yamaguchi J, Cassaca R, Zerbib L, Magassa S, Morin G, Asnafi V, Villarese P, Kaltenbach S, Fraitag S, Duong JP, Broissand C, Boccara O, Soupre V, Bonnotte B, Chopinet C, Mirault T, Legendre C, Guibaud L, Canaud G. Alpelisib administration reduced lymphatic malformations in a mouse model and in patients. Sci Transl Med. 2021 Oct 6;13(614):eabg0809. doi: 10.1126/scitranslmed.abg0809. Epub 2021 Oct 6.
- Background: PubMed 35080595Morin G, Degrugillier-Chopinet C, Vincent M, Fraissenon A, Aubert H, Chapelle C, Hoguin C, Dubos F, Catteau B, Petit F, Mezel A, Domanski O, Herbreteau G, Alesandrini M, Boddaert N, Boutry N, Broissand C, Han TK, Branle F, Sarnacki S, Blanc T, Guibaud L, Canaud G. Treatment of two infants with PIK3CA-related overgrowth spectrum by alpelisib. J Exp Med. 2022 Mar 7;219(3):e20212148. doi: 10.1084/jem.20212148. Epub 2022 Jan 26.
- Results publication: PubMed 29899452Venot Q, Blanc T, Rabia SH, Berteloot L, Ladraa S, Duong JP, Blanc E, Johnson SC, Hoguin C, Boccara O, Sarnacki S, Boddaert N, Pannier S, Martinez F, Magassa S, Yamaguchi J, Knebelmann B, Merville P, Grenier N, Joly D, Cormier-Daire V, Michot C, Bole-Feysot C, Picard A, Soupre V, Lyonnet S, Sadoine J, Slimani L, Chaussain C, Laroche-Raynaud C, Guibaud L, Broissand C, Amiel J, Legendre C, Terzi F, Canaud G. Targeted therapy in patients with PIK3CA-related overgrowth syndrome. Nature. 2018 Jun;558(7711):540-546. doi: 10.1038/s41586-018-0217-9. Epub 2018 Jun 13.
- Results publication: PubMed 28431241Manning BD, Toker A. AKT/PKB Signaling: Navigating the Network. Cell. 2017 Apr 20;169(3):381-405. doi: 10.1016/j.cell.2017.04.001.
- Individual participant dataSharing planned: No
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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.
Guillaume Canaud, MD,PHD principal investigator
Institut National de la Santé Et de la Recherche Médicale, France
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of PIK3CA-related Overgrowth Spectrum and CLOVES Syndrome, run by Institut National de la Santé Et de la Recherche Médicale, France at 1 site 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 4 inclusion and 2 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 23 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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?
Description of patients with overgrowth syndromes (time frame: 5 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05563831, which also lists 6 linked publications.
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 23 Feb 2026.