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

NCT ID: NCT05563831

Last Updated: 2023-04-07

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 2500 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2023-02-21
• Study Completion Date: 2028-12-31

Brief 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.

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; Vascular Malformations; Lymphatic Malformation; Venous Malformation

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: OTHER

Interventions

national registry

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

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

1. Affiliated to the French healthcare insurance system.

2. Pediatric and adult patients

3. Clinical diagnosis of overgrowth syndrome

4. Written informed consent from adult patients and from both parents of pediatric patients.

Exclusion Criteria

1. Person subject to a judicial safeguard measure

2. Inability to give informed consent

• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Institut National de la Santé Et de la Recherche Médicale, France

OTHER_GOV

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Guillaume Canaud, MD,PHD

Role: PRINCIPAL_INVESTIGATOR

Institut National de la Santé Et de la Recherche Médicale, France

Locations

Translational medicine and Targeted therapies unit, Hôpital Necker Enfants Malades

Paris, , France

Site Status: RECRUITING

Countries

France

Central Contacts

Guillaume GC Canaud, MD,PHD

Role: CONTACT

guillaume.canaud@inserm.fr

0140615425

Nadia NB BAHI-BUISSON, MD,PHD

Role: CONTACT

nadia.bahi-buisson@aphp.fr

Facility Contacts

Guillaume Canaud, MD, PHD

Role: primary

guillaume.canaud@inserm.fr

+33144494976

References

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.

Reference Type: BACKGROUND

PMID: 34238334 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 34530449 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 34613809 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 35080595 (View on PubMed)

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.

Reference Type: RESULT

PMID: 29899452 (View on PubMed)

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.

Reference Type: RESULT

PMID: 28431241 (View on PubMed)

Other Identifiers

C20-09

Identifier Type: -

Identifier Source: org_study_id