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

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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

Tracking Information
First Submitted Date March 4, 2014
First Posted Date July 1, 2015
Last Update Posted Date November 9, 2015
Study Start Date November 2015
Estimated Primary Completion Date July 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: June 30, 2015)
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
Original Primary Outcome Measures Same as current
Change History
Current Secondary Outcome Measures
 (submitted: June 30, 2015)
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
Original Secondary Outcome Measures Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title Hormonal Sensitivity in Patients With Noonan and LEOPARD Syndromes
Official Title Consequences of Noonan Syndrome/LEOPARD Syndrome Associated Shp2 Mutations on Different Signaling Pathways Activation: Relationship With Hormonal Sensitivity
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.

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
Study Design Observational Model: Case-Control
Time Perspective: Cross-Sectional
Target Follow-Up Duration Not Provided
Biospecimen Retention:   Samples Without DNA
Description:
Fibroblasts, adipocytes, serum
Sampling Method Non-Probability Sample
Study Population Data collected in patients with Noonan or LEOPARD syndromes will be compared to data of healthy subjects.
Condition
  • Noonan Syndrome
  • LEOPARD Syndrome
Intervention Not Provided
Study Groups/Cohorts
  • Noonan syndrome
    Patients with Noonan syndrome
  • LEOPARD syndrome
    Patients with LEOPARD syndromes
  • Controls
    Healthy subjects
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Unknown status
Estimated Enrollment
 (submitted: June 30, 2015)
27
Original Estimated Enrollment Same as current
Estimated Study Completion Date July 2018
Estimated Primary Completion Date July 2018   (Final data collection date for primary outcome measure)
Eligibility 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

Sex/Gender
Sexes Eligible for Study: All
Ages 5 Years to 15 Years   (Child)
Accepts Healthy Volunteers Yes
Contacts Contact information is only displayed when the study is recruiting subjects
Listed Location Countries France
Removed Location Countries  
 
Administrative Information
NCT Number NCT02486731
Other Study ID Numbers C13-59
2013-A01428-37 ( Registry Identifier: IDRCB )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement Not Provided
Responsible Party Institut National de la Santé Et de la Recherche Médicale, France
Study Sponsor Institut National de la Santé Et de la Recherche Médicale, France
Collaborators Not Provided
Investigators Not Provided
PRS Account Institut National de la Santé Et de la Recherche Médicale, France
Verification Date November 2015