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NCT Number: NCT02383316

Study of Metabolic Modifications in Children With Noonan Syndrome

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.

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Key information

Conditions

CHILD Syndrome Cardiovascular Abnormalities Cardiovascular Diseases Congenital Abnormalities Congenital Hemidysplasia with Ichthyosiform Erythroderma and Limb Defects Congenital, Hereditary, and Neonatal Diseases and Abnormalities Connective Tissue Diseases Craniofacial Abnormalities Glucose Metabolism Disorders Heart Defects, Congenital Heart Diseases Hyperinsulinism Insulin Resistance Metabolic Diseases Musculoskeletal Abnormalities Musculoskeletal Diseases Noonan Syndrome Nutritional and Metabolic Diseases Skin and Connective Tissue Diseases

Age range

7 year–18 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

CHU Toulouse - Hôpital des Enfants

Toulouse, 31052, France

About this study

Differential hormone sensitivity is associated with Noonan Syndrome and participates in the development of some symptoms. The investigators have demonstrated that MAPK upregulation in Noonan Syndrome is responsible for partial growth hormone (GH) insensitivity, and subsequent growth retardation.

Clinical traits evocative of energy metabolism dysfunctions have been recently reported in Noonan Syndrome patients, although the origins and consequences of these metabolic changes have not been documented to date. The aim of this study is to explore the metabolic status of children with Noonan Syndrome.

Children with Noonan Syndrome will be compared with age- and sex-matched healthy children. The investigators 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).

The study will include only one visit.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

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

Exclusion criteria

  • Chronic disease associated with variation of insulin sensitivity: body mass
  • Treatment associated with variation of insulin sensitivity: corticoid treatment > 5 days preceding the study inclusion
  • Tumoral disease (leukemia) in treatment

Treatment and study plan

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.

Primary outcomes

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

    Time frame: T0 on an empty stomach

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

Secondary outcomes

  1. Insulin sensitivity determined with HOMA index

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

    Glucose and insulin levels will be measured at time points 0, 90 and 120 min (children weigh 17-25kg) or 30, 60, 90 and 120 min (children weigh >25kg) after 1.75g/kg glucose administration (oral glucose tolerance test)

  2. Blood pressure

    Time frame: T0

    These tests will be done on arrival in hospital before the oral glucose tolerance test. Blood pressure is measured after 10 minutes of rest in the elongated child.

  3. Blood level of hemoglobin A1c and ghrelin

    Time frame: T0 on an empty stomach

    Blood sample realised at T0 before the oral glucose tolerance test.

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

    Time frame: T0

    This test will be realised during hospitalisation day, except if it has been done up to 6 months prior to enrollment.

  5. Body mass index

    Time frame: T0

    This test will be realised during hospitalisation day, at patient arrival.

  6. Waist circumference

    Time frame: T0

    This test will be realised during hospitalisation day, at patient arrival.

  7. Blood level of leptin

    Time frame: T0 on an empty stomach

    Blood sample realised at T0 before the oral glucose tolerance test.

  8. Blood level of ghrelin

    Time frame: T0 on an empty stomach

    Blood sample realised at T0 before the oral glucose tolerance test.

Sponsors and collaborators

Lead sponsor

University Hospital, Toulouse

Other

Registry information

Acronym: MetabNoonan

Important dates

Study start
2015
Primary completion
2016
Study completion
2016
First posted
Mar 9, 2015
Registry last updated
Dec 15, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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