Growth and Asymmetric diMethylArginine

Study Overview
=================
Brief Summary
-----------------
Principal objective : Validation of a handy biochemical parameter, plasma concentration of Asymmetric DimethylArginine (ADMA), based on a recognize biochemical parameter, the dilation of the brachial artery, at ultrasound examination, after the deflation of a cushion to evaluate artery dysfunction (vascular suffering) in growth diseases, growth hormone deficiency (GHD) and intrauterine growth retardation (IUGR) Secondary objectives: Comparison of ADMA plasma concentrations with dose of matched healthy control children Investigation of the mechanisms of arterial dysfunction, inflammation, oxidative stress and insulin resistance.

Official Title
-----------------
Validation of the Dosage of Asymmetric Dimethylarginine (ADMA) Plasma in the Assessment of Endothelial Dysfunction During Growth Hormone Deficiency and Intrauterine Growth Retardation

Conditions
-----------------
Growth Hormone Deficiency, Small-for-gestational Age

Intervention / Treatment
-----------------
* Diagnostic Test: arterial doppler ultrasound


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Group A: GHD, defined by 2 GH peaks less than 6.6 ng/ml (20 mU/L) at two stimulation tests Group B: IUGR, defined by a birth length and/or a birth weight inferior to - 2 SD for gestational age according to Usher and McLean charts Group C: Control children matched to children matched to subjects of groups A and B, according to gender and age Informed consent signed by representative of the parental authority Exclusion Criteria: Chronic disabling disease (ex: diabetes, severe asthma) Evolving cancer Severe psychiatric disorder (ex: autism, schizophrenia; severe depression) Hypothalamic tumor (ex: craniopharyngioma) Anamnesis of cranial irradiation Overweight, obesity or thinness Precocious puberty Non-replacing therapy by glucocorticoids or sex steroids less than 1 month before the exploration Anterior treatment by recombinant human GH Other conditions, treatments or habits impacting arterial reactivity: acrocyanosis, cryoglobulinemia, beta adrenergic blocking habits, tobacco smoking or other drug addictions, dyslipidemia Pregnancy or lactation Acute infection less than three weeks before the investigation Participation to a therapeutic protocol Impossibility for the representatives of the parental authority to understand the objectives of the protocol Absence of social security coverage. Refusal by the parents to sign the informed consent or oral refusal by the child to participate to the study

Ages Eligible for Study
-----------------
Minimum Age: 3 Years
Maximum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| growth hormone deficiency<br> | Diagnostic Test: arterial doppler ultrasound<br>* doppler ultrasound<br>|
| small for gestational age<br> | Diagnostic Test: arterial doppler ultrasound<br>* doppler ultrasound<br>|
| matched controls<br> | Diagnostic Test: arterial doppler ultrasound<br>* doppler ultrasound<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma Asymmetric Dimethylarginine (ADMA) | Correlation between ADMA (Asymmetric DimethylArginine, a collateral derivate of nitric oxide metabolism) levels and the percentage of dilation of the brachial artery at Doppler ultrasound examination. The dosage will be performed by high pressure liquid chromatography followed by tandem mass spectrometry (HPLC-MS / MS) | At baseline | 
| Percentage of dilation of the brachial artery at Doppler ultrasound examination. | Correlation between ADMA (Asymmetric DimethylArginine, a collateral derivate of nitric oxide metabolism) levels and the percentage of dilation of the brachial artery at Doppler ultrasound examination. | At baseline. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference of ADMA concentration between the patient and the control groups |  | At baseline | 
| Correlation of ADMA levels with diverse cardiovascular risk factors |  | At baseline | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
endothelial dysfunction, doppler ultrasound examination, nitric oxide