Study of Metabolic Modifications in Children With Noonan Syndrome

NCT02383316 | Completed

• 2 other identifiers: RC31/14/7315AOL
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

Noonan syndrome (NS) is a rare genetic disease (incidence 1/2500 live births) characterized by the association of craniofacial manifestations, cardiopathies, short stature, and tumor predisposition. The genetic causes of Noonan Syndrome are mutations of genes involved in the Ras/Mitogen-Activated Protein Kinases (MAPK) pathway, mainly the gene encoding the tyrosine phosphatase Shp2 (50% of patients).Shp2 appears to be involved in many facets of energy metabolism control (glucose homeostasis, adipose tissue function…), through mechanisms that are poorly understood. Several metabolic anomalies (reduced adiposity, improved glucose tolerance) have been recently identified in an original mouse model carrying Shp2 mutation. Moreover, recent clinical survey has shown that adult Noonan Syndrome patients are protected from developping overweight and obesity when compared to the general population. However, the metabolic status associated with Noonan Syndrome condition has not been explored to date.

Conditions

Child Syndrome

Keywords

Insulin sensitivity; Metabolism; Noonan syndrome; Shp2

Outcome Measures

Primary Outcomes (1)

• Insulin sensitivity determined from the calculation of the Quantitative insulin sensitivity check index (QUICKI).

  Measured at the patient's arrival (TO) from the blood levels of glucose and fasting insulin

  T0 on an empty stomach

Secondary Outcomes (8)

• Insulin sensitivity determined with HOMA index

  T30, T60, T90 and T120 minutes after oral glucose tolerance test

• Blood pressure

  T0

• Blood level of hemoglobin A1c and ghrelin

  T0 on an empty stomach

• Body composition as fat mass and muscle mass measured by dual-energy x-ray absorptiometry (DXA)

  T0

• Body mass index

  T0

Study Arms (1)

Noonan Syndrome Children

EXPERIMENTAL

Children with Noonan Syndrome will be compared with age- and sex-matched healthy children. We hypothesize than Noonan Syndrome children have an increased insulin sensitivity compared to GHD children. Study parameters will be collected including: clinical measurements (height, weight, body mass index, waist circumference, and blood pressure), glucose and insulin levels at baseline and after an oral glucose tolerance test (OGTT), body composition measured by dual-energy x-ray absorptiometry (DXA).

Other: Oral Glucose tolerance test

Interventions

Oral Glucose tolerance test OTHER

Oral glucose tolerance test (OGTT): glucose and insulin levels will be measured at time points 0, 90 and 120 min or 30, 60, 90 and 120 after 1.75 g/Kg (max 75 g) glucose administration depending of the patient weight.

Noonan Syndrome Children

Eligibility Criteria

• Age: 7 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Noonan syndrome genetically confirmed
• Informed consent obtained from children and parents

You may not qualify if:

• Chronic disease associated with variation of insulin sensitivity: body mass
• Tumoral disease (leukemia) in treatment

Sponsors & Collaborators

• University Hospital, Toulouse: lead

Study Sites (1)

CHU Toulouse - Hôpital des Enfants

Toulouse, 31052, France

Location

Related Publications (1)

• Paccoud R, Saint-Laurent C, Piccolo E, Tajan M, Dortignac A, Pereira O, Le Gonidec S, Baba I, Gelineau A, Askia H, Branchereau M, Charpentier J, Personnaz J, Branka S, Auriau J, Deleruyelle S, Canouil M, Beton N, Salles JP, Tauber M, Weill J, Froguel P, Neel BG, Araki T, Heymes C, Burcelin R, Castan I, Valet P, Dray C, Gautier EL, Edouard T, Pradere JP, Yart A. SHP2 drives inflammation-triggered insulin resistance by reshaping tissue macrophage populations. Sci Transl Med. 2021 Apr 28;13(591):eabe2587. doi: 10.1126/scitranslmed.abe2587. Epub 2021 Apr 28.

  PMID: 33910978 RESULT

MeSH Terms

Conditions

Congenital Hemidysplasia with Ichthyosiform Erythroderma and Limb Defects; Insulin Resistance; Noonan Syndrome

Interventions

Glucose Tolerance Test

Condition Hierarchy (Ancestors)

Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Craniofacial Abnormalities; Musculoskeletal Abnormalities; Musculoskeletal Diseases; Heart Defects, Congenital; Cardiovascular Abnormalities; Cardiovascular Diseases; Heart Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Connective Tissue Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Blood Chemical Analysis; Clinical Chemistry Tests; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Endocrine; Investigative Techniques

Study Officials

• Thomas Edouard, MD

  CHU Toulouse, Hôpital des Enfants

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 23, 2014
• First Posted: March 9, 2015
• Study Start: January 1, 2015
• Primary Completion: June 1, 2016
• Study Completion: June 1, 2016
• Last Updated: December 15, 2025

Record last verified: 2018-02

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)