ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02486731
Recruitment Status : Unknown
Verified November 2015 by Institut National de la Santé Et de la Recherche Médicale, France.
Recruitment status was:  Not yet recruiting
First Posted : July 1, 2015
Last Update Posted : November 9, 2015
Sponsor:
Information provided by (Responsible Party):
Institut National de la Santé Et de la Recherche Médicale, France

Brief 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.


Condition or disease
Noonan Syndrome LEOPARD Syndrome

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
Estimated Enrollment : 27 participants
Observational Model: Case Control
Time Perspective: Cross-Sectional
Official Title: Consequences of Noonan Syndrome/LEOPARD Syndrome Associated Shp2 Mutations on Different Signaling Pathways Activation: Relationship With Hormonal Sensitivity
Study Start Date : November 2015
Estimated Primary Completion Date : July 2018
Estimated Study Completion Date : July 2018


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



Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. 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


Biospecimen Retention:   Samples Without DNA
Fibroblasts, adipocytes, serum


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   5 Years to 15 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
Data collected in patients with Noonan or LEOPARD syndromes will be compared to data of healthy subjects.
Criteria

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


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02486731


Contacts
Contact: Jean Pierre Salles, PU-PH 0534558727 salles.jp@chu-toulouse.fr

Locations
France
CIC de Toulouse- Unité pediatrique Not yet recruiting
Toulouse, France, 31059
Sponsors and Collaborators
Institut National de la Santé Et de la Recherche Médicale, France

Responsible Party: Institut National de la Santé Et de la Recherche Médicale, France
ClinicalTrials.gov Identifier: NCT02486731     History of Changes
Other Study ID Numbers: C13-59
2013-A01428-37 ( Registry Identifier: IDRCB )
First Posted: July 1, 2015    Key Record Dates
Last Update Posted: November 9, 2015
Last Verified: November 2015

Keywords provided by Institut National de la Santé Et de la Recherche Médicale, France:
Hormonal sensitivity
bone growth

Additional relevant MeSH terms:
Syndrome
Noonan Syndrome
LEOPARD Syndrome
Hypersensitivity
Disease
Pathologic Processes
Immune System Diseases
Craniofacial Abnormalities
Musculoskeletal Abnormalities
Musculoskeletal Diseases
Heart Defects, Congenital
Cardiovascular Abnormalities
Cardiovascular Diseases
Heart Diseases
Congenital Abnormalities
Connective Tissue Diseases
Pulmonary Valve Stenosis
Heart Valve Diseases
Abnormalities, Multiple
Lentigo
Melanosis
Hyperpigmentation
Pigmentation Disorders
Skin Diseases