Hormonal Sensitivity in Patients With Noonan and LEOPARD Syndromes

Noonan Syndrome Clinical Trial

— NOLEO  

Official title:

Consequences of Noonan Syndrome/LEOPARD Syndrome Associated Shp2 Mutations on Different Signaling Pathways Activation: Relationship With Hormonal Sensitivity

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02486731
• Other study ID #: C13-59
• Secondary ID: 2013-A01428-37
• Status: Completed
• Start date: December 16, 2015
• Est. completion date: December 2018

Study information

• Verified date: August 2021
• Source: Institut National de la Santé Et de la Recherche Médicale, France
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Noonan and LEOPARD syndromes share, with variable severity, different clinical traits, notably craniofacial manifestations, cardiopathies, short stature, and juvenile cancers.

The main genetic cause of these syndromes is missense mutation of the gene encoding the ubiquitous tyrosine phosphatase Shp2, found in more than half the patients with NS and in 80% of LS cases. Shp2 plays pivotal roles in development, growth, and metabolism by regulating key signalling pathways (Ras/Mitogen activated protein kinase (MAPK), Phosphoinositide-3 Kinases (PI3K)/Akt) in response to growth factors/hormones. Deregulation of these signalling pathways has been causally linked to NS and LS pathophysiology.

This project aims at better understanding hormonal sensitivity abnormalities in patients with Noonan syndrome (NS) or LEOPARD syndrome (LS) caused by mutations of the tyrosine phosphatase Shp2.

To reach this goal, the investigators will take advantage of different tissues (fibroblasts ± adipocytes) from patients with NS / LS compared to healthy controls.

All patients will have a skin biopsy and only patients about to undergo surgery will have a adipose tissue biopsy.

Description:

The activation of different signaling pathways (Ras/MAPK, PI3K/Akt) in response to growth factors/hormones (growth hormone, insulin) in fibroblasts and/or in adipocytes from patients with NS or LS will be compared to those of healthy subjects.

These data will be correlated to clinical, hormonal, and biochemical characteristics of patients

Recruitment information / eligibility

• Status: Completed
• Enrollment: 27
• Est. completion date: December 2018
• Est. primary completion date: December 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 5 Years to 15 Years

Eligibility

Inclusion Criteria:

Patients with Noonan syndrome (NS) or LEOPARD syndrome (LS):

• female or male

• age between 5 to 15 years

• clinical diagnosis of NS or LS according to published criteria

• signed informed consent of parents

Healthy controls:

• female or male

• age between 5 to 15 years

• no personal history of syndrome or chronic disease

• planned surgical procedure

• signed informed consent of parents

Exclusion Criteria:

• age below 5 or above 15 years

• pregnancy

In healthy controls: syndromic or chronic disease

Related Conditions & MeSH terms

• Hypersensitivity
• LEOPARD Syndrome
• Noonan Syndrome
• Syndrome

Locations

Country	Name	City	State
France	CIC de Toulouse- Unité pediatrique	Toulouse

Sponsors (1)

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

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Phosphorylation of Erk and Akt in fibroblasts	To evaluate different signaling pathways activation (Ras/MAPK, PI3K/Akt) in response to growth factors/hormones (growth hormone, insulin) in fibroblasts from patients with NS or LS compared to healthy controls	Baseline
Secondary	Phosphorylation of Erk and Akt in adipocytes	To evaluate different signaling pathways activation (Ras/MAPK, PI3K/Akt) in response to growth factors/hormones (growth hormone, insulin) in adipocytes from patients with NS or LS compared to healthy controls	Baseline