Hormonal Sensitivity in Patients With Noonan and LEOPARD Syndromes (NOLEO)

August 25, 2021 updated by: Institut National de la Santé Et de la Recherche Médicale, France

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

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.

Study Overview

Status

Completed

Conditions

Detailed 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

Study Type

Observational

Enrollment (Actual)

27

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Toulouse, France, 31059
        • CIC de Toulouse- Unité pediatrique

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

3 years to 13 years (Child)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Data collected in patients with Noonan or LEOPARD syndromes will be compared to data of healthy subjects.

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Case-Control
  • Time Perspectives: Cross-Sectional

Cohorts and Interventions

Group / Cohort
Controls
Healthy subjects
Noonan syndrome
Patients with Noonan syndrome
LEOPARD syndrome
Patients with LEOPARD syndromes

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Phosphorylation of Erk and Akt in fibroblasts
Time Frame: Baseline
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Phosphorylation of Erk and Akt in adipocytes
Time Frame: Baseline
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

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

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 16, 2015

Primary Completion (Actual)

December 1, 2018

Study Completion (Actual)

December 1, 2018

Study Registration Dates

First Submitted

March 4, 2014

First Submitted That Met QC Criteria

June 30, 2015

First Posted (Estimate)

July 1, 2015

Study Record Updates

Last Update Posted (Actual)

August 26, 2021

Last Update Submitted That Met QC Criteria

August 25, 2021

Last Verified

August 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • C13-59
  • 2013-A01428-37 (Registry Identifier: IDRCB)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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