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

Vascular Malformations Clinical Trial

— COSY  

Official title:

Evaluation Nationale Des Enfants et Adultes Avec Syndromes d'Hypercroissance Dysharmonieuse National Evaluation of Patients With PIK3CA-Related Overgrowth Spectrum (PROS)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05563831
• Other study ID #: C20-09
• Status: Recruiting
• Start date: February 21, 2023
• Est. completion date: December 31, 2028

Study information

• Verified date: April 2023
• Source: Institut National de la Santé Et de la Recherche Médicale, France
• Contact: Guillaume GC Canaud, MD,PHD
• Phone: 0140615425
• Email: guillaume.canaud[@]inserm.fr
• Is FDA regulated: No
• Study type: Observational

Clinical 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 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 2500
• Est. completion date: December 31, 2028
• Est. primary completion date: December 31, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

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

Related Conditions & MeSH terms

• CLOVES Syndrome
• Congenital Abnormalities
• Klippel Trenaunay Syndrome
• Lymphangioma
• Lymphatic Abnormalities
• Lymphatic Malformation
• Syndrome
• Vascular Malformations
• Venous Malformation

Intervention

Other:
• national registry
The investigators will collect demographic, clinical, biological and imaging characteristics of patients with PROS.

Locations

Country	Name	City	State
France	Translational medicine and Targeted therapies unit, Hôpital Necker Enfants Malades	Paris

Sponsors (1)

Lead Sponsor	Collaborator
Institut National de la Santé Et de la Recherche Médicale, France

Country where clinical trial is conducted

France, 

References & Publications (6)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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-Feys — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Description of patients with overgrowth syndromes	Clinical and molecular characterization of patients with overgrowth syndromes will be performed.	5 years
Secondary	Prevalence of overgrowth syndromes in France	An estimation of the prevalence of overgrowth syndromes in France will be done	5 years
Secondary	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)	5 years
Secondary	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.	5 years
Secondary	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.	5 years