Growth and Asymmetric diMethylArginine (GAMMA)

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

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.

Study Overview

• Status: Unknown
• Conditions: Growth Hormone Deficiency; Small-for-gestational Age
• Intervention / Treatment: Diagnostic test: arterial doppler ultrasound

• Study Type: Observational
• Enrollment (Actual): 23

Contacts and Locations

Study Locations

• France
  • Lille, France
    • Hôpital Jeanne de Flandre - CHRU de Lille
  • Toulouse, France
    • CHU Purpan

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 years to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

pediatric patients with growth disorders and matched control children

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
growth hormone deficiency	Diagnostic test: arterial doppler ultrasound; doppler ultrasound
small for gestational age	Diagnostic test: arterial doppler ultrasound; doppler ultrasound
matched controls	Diagnostic test: arterial doppler ultrasound; doppler ultrasound

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	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

Collaborators and Investigators

• Sponsor: University Hospital, Lille
• Investigators: Principal Investigator: Jacques Weill, MD, PhD, University Hospital, Lille

Study record dates

Study Major Dates

• Study Start: June 1, 2014
• Primary Completion (Anticipated): December 1, 2020
• Study Completion (Anticipated): December 1, 2020

Study Registration Dates

• First Submitted: January 10, 2018
• First Submitted That Met QC Criteria: February 2, 2018
• First Posted (Actual): February 5, 2018

Study Record Updates

• Last Update Posted (Actual): August 25, 2020
• Last Update Submitted That Met QC Criteria: August 24, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Keywords: endothelial dysfunction; nitric oxide; doppler ultrasound examination
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Endocrine System Diseases; Musculoskeletal Diseases; Hypothalamic Diseases; Bone Diseases; Bone Diseases, Endocrine; Pituitary Diseases; Dwarfism; Bone Diseases, Developmental; Hypopituitarism; Dwarfism, Pituitary
• Other Study ID Numbers: 2012_61; 2013-A00830-45 (Other Identifier: ID-RCB number, ANSM)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No