Clinical trial NCT05563831: National Evaluation of Patients With PIK3CA-Related Overgrowth Spectrum (PROS)
Official title: Evaluation Nationale Des Enfants et Adultes Avec Syndromes d'Hypercroissance Dysharmonieuse National Evaluation of Patients With PIK3CA-Related Overgrowth Spectrum (PROS)
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: 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
Lead sponsor: Institut National de la Santé Et de la Recherche Médicale, France
Sponsor class: OTHER_GOV
First posted: 2022-10-03
Enrollment: 2500
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: OTHER
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.

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.

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

Primary outcomes:
measure: Description of patients with overgrowth syndromes
timeFrame: 5 years
Secondary outcomes:
measure: Prevalence of overgrowth syndromes in France
timeFrame: 5 years
measure: Biobanking of samples derived from patients with overgrowth syndromes
timeFrame: 5 years
measure: Description of patient cares: mumber of consultations and hospitalizations, number of treatment lines, grouping of patients by type of course (clusters)
timeFrame: 5 years
measure: Economic evaluation of cares for patients with overgrowth syndromes: cost of care, per period and cumulative.
timeFrame: 5 years
Other outcomes:
Locations:
city: Paris
country: France
facility: Translational medicine and Targeted therapies unit, Hôpital Necker Enfants Malades
Study officials:
affiliation: Institut National de la Santé Et de la Recherche Médicale, France
name: Guillaume Canaud, MD,PHD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
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.
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.
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.
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-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.
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.