ClinicalTrials.gg
CompletedNCT05563831COSYUpdated Feb 23, 2026

National Evaluation of Patients With PIK3CA-Related Overgrowth Spectrum (PROS)

An observational study in PIK3CA-related Overgrowth Spectrum, CLOVES Syndrome and Klippel Trenaunay Syndrome, sponsored by Institut National de la Santé Et de la Recherche Médicale, France. Completed at 1 site in France. Per ClinicalTrials.gov, last updated 2026-02-23.

Sponsored by Institut National de la Santé Et de la Recherche Médicale, France · Observational

Study type
Observational
Model
Cohort
Time perspective
Other
Enrollment
28
Sex
All
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Study 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 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.

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Conditions studied

  • PIK3CA-related Overgrowth Spectrum
  • CLOVES Syndrome
  • Klippel Trenaunay Syndrome
  • Megalencephaly
  • MCAP
  • Macrodactyly
  • Vascular Malformations
  • Lymphatic Malformation
  • Venous Malformation

Keywords

  • PIK3CA
  • Related Overgrowth Syndrome
  • PIK3CA/AKT/mTOR pathway
  • clinical diagnosis
  • Biobank
  • Patient Stratification
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In context

Klippel-Trenaunay-Weber Syndrome

8 studies on the registry are indexed under Klippel-Trenaunay-Weber Syndrome; 4 are open to participants now.

Browse Klippel-Trenaunay-Weber Syndrome studies →

Lead sponsor

Institut National de la Santé Et de la Recherche Médicale, France is the lead sponsor of 378 studies on the registry; 81 are open to participants now.

Counted across the registry records on this site, refreshed daily.

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Who can participate

Ages eligible
Child (0–17), Adult (18–64), Older adult (65+)
Sexes eligible
All
Accepts healthy volunteers
No
Sampling method
Non-probability sample

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.

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

Inclusion criteria

  1. Affiliated to the French healthcare insurance system.
  2. Pediatric and adult patients
  3. Clinical diagnosis of overgrowth syndrome
  4. Written from adult patients and from both parents of pediatric patients.

Exclusion criteria

Exclusion Criteria:

  1. Person subject to a judicial safeguard measure
  2. Inability to give
Terms in these criteria, in plain language(1)

Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.

Informed consent

Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.

You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.

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Study design

Observational model
Cohort
Time perspective
Other
Enrollment
28 participants (actual)
Patient registry
No
Biospecimen retention
Samples with dna

Interventions

  • Othernational registry

    The investigators will collect demographic, clinical, biological and imaging characteristics of patients with PROS.

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What researchers measure

Primary outcomes

  1. Description of patients with overgrowth syndromes

    Clinical and molecular characterization of patients with overgrowth syndromes will be performed.

    Time frame: 5 years

Secondary outcomes

  1. Prevalence of overgrowth syndromes in France

    An estimation of the prevalence of overgrowth syndromes in France will be done

    Time frame: 5 years

  2. 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)

    Time frame: 5 years

  3. 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.

    Time frame: 5 years

  4. 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.

    Time frame: 5 years

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Study locations

1 site
  • Translational medicine and Targeted therapies unit, Hôpital Necker Enfants Malades
    Paris, 75015, France
08

References and documents

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 34238334 ↗
  • Morin 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 34530449 ↗
  • Delestre 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 34613809 ↗
  • Morin 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 35080595 ↗
  • Venot 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 29899452 ↗
  • Manning 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 ↗

Individual participant data

Plan to share: No

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Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Feb 23, 2026, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
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Registry details

Key details

Study ID
NCT05563831
Responsible party
Sponsor
First posted
Oct 3, 2022
Start date
Feb 21, 2023
Primary completion
Jun 7, 2023
Completion
Jun 7, 2023
Last update
Feb 23, 2026

Study contacts

Guillaume Canaud, MD,PHD
principal investigator · Institut National de la Santé Et de la Recherche Médicale, France

Oversight

Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in Apr 2023. You cannot join it, but the record below documents what was studied.

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