Study of Metabolic Modifications in Children With Noonan Syndrome (MetabNoonan)
Primary Purpose
Child Syndrome
Status
Completed
Phase
Not Applicable
Locations
France
Study Type
Interventional
Intervention
Oral Glucose tolerance test
Sponsored by
About this trial
This is an interventional basic science trial for Child Syndrome focused on measuring Insulin sensitivity, Metabolism, Noonan syndrome, Shp2
Eligibility Criteria
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
Sites / Locations
- CHU Toulouse - Hôpital des Enfants
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Noonan Syndrome Children
Arm Description
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).
Outcomes
Primary Outcome Measures
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
Secondary Outcome Measures
Insulin sensitivity determined with HOMA index
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)
Blood pressure
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.
Blood level of hemoglobin A1c and ghrelin
Blood sample realised at T0 before the oral glucose tolerance test.
Body composition as fat mass and muscle mass measured by dual-energy x-ray absorptiometry (DXA)
This test will be realised during hospitalisation day, except if it has been done up to 6 months prior to enrollment.
Body mass index
This test will be realised during hospitalisation day, at patient arrival.
Waist circumference
This test will be realised during hospitalisation day, at patient arrival.
Blood level of leptin
Blood sample realised at T0 before the oral glucose tolerance test.
Blood level of ghrelin
Blood sample realised at T0 before the oral glucose tolerance test.
Full Information
NCT ID
NCT02383316
First Posted
December 23, 2014
Last Updated
February 2, 2018
Sponsor
University Hospital, Toulouse
1. Study Identification
Unique Protocol Identification Number
NCT02383316
Brief Title
Study of Metabolic Modifications in Children With Noonan Syndrome
Acronym
MetabNoonan
Official Title
Study of Metabolic Modifications in Children With Noonan Syndrome
Study Type
Interventional
2. Study Status
Record Verification Date
February 2018
Overall Recruitment Status
Completed
Study Start Date
January 2015 (undefined)
Primary Completion Date
June 2016 (Actual)
Study Completion Date
June 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Hospital, Toulouse
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
Detailed Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Child Syndrome
Keywords
Insulin sensitivity, Metabolism, Noonan syndrome, Shp2
7. Study Design
Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
20 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Noonan Syndrome Children
Arm Type
Experimental
Arm Description
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).
Intervention Type
Other
Intervention Name(s)
Oral Glucose tolerance test
Intervention Description
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 Outcome Measure Information:
Title
Insulin sensitivity determined from the calculation of the Quantitative insulin sensitivity check index (QUICKI).
Description
Measured at the patient's arrival (TO) from the blood levels of glucose and fasting insulin
Time Frame
T0 on an empty stomach
Secondary Outcome Measure Information:
Title
Insulin sensitivity determined with HOMA index
Description
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)
Time Frame
T30, T60, T90 and T120 minutes after oral glucose tolerance test
Title
Blood pressure
Description
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.
Time Frame
T0
Title
Blood level of hemoglobin A1c and ghrelin
Description
Blood sample realised at T0 before the oral glucose tolerance test.
Time Frame
T0 on an empty stomach
Title
Body composition as fat mass and muscle mass measured by dual-energy x-ray absorptiometry (DXA)
Description
This test will be realised during hospitalisation day, except if it has been done up to 6 months prior to enrollment.
Time Frame
T0
Title
Body mass index
Description
This test will be realised during hospitalisation day, at patient arrival.
Time Frame
T0
Title
Waist circumference
Description
This test will be realised during hospitalisation day, at patient arrival.
Time Frame
T0
Title
Blood level of leptin
Description
Blood sample realised at T0 before the oral glucose tolerance test.
Time Frame
T0 on an empty stomach
Title
Blood level of ghrelin
Description
Blood sample realised at T0 before the oral glucose tolerance test.
Time Frame
T0 on an empty stomach
10. Eligibility
Sex
All
Minimum Age & Unit of Time
7 Years
Maximum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Thomas Edouard, MD
Organizational Affiliation
CHU Toulouse, Hôpital des Enfants
Official's Role
Principal Investigator
Facility Information:
Facility Name
CHU Toulouse - Hôpital des Enfants
City
Toulouse
ZIP/Postal Code
31052
Country
France
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
21396583
Citation
Tartaglia M, Gelb BD, Zenker M. Noonan syndrome and clinically related disorders. Best Pract Res Clin Endocrinol Metab. 2011 Feb;25(1):161-79. doi: 10.1016/j.beem.2010.09.002.
Results Reference
background
PubMed Identifier
19467855
Citation
Tidyman WE, Rauen KA. The RASopathies: developmental syndromes of Ras/MAPK pathway dysregulation. Curr Opin Genet Dev. 2009 Jun;19(3):230-6. doi: 10.1016/j.gde.2009.04.001. Epub 2009 May 19.
Results Reference
background
PubMed Identifier
15574420
Citation
Montagner A, Yart A, Dance M, Perret B, Salles JP, Raynal P. A novel role for Gab1 and SHP2 in epidermal growth factor-induced Ras activation. J Biol Chem. 2005 Feb 18;280(7):5350-60. doi: 10.1074/jbc.M410012200. Epub 2004 Dec 1.
Results Reference
background
PubMed Identifier
11134009
Citation
Yart A, Laffargue M, Mayeux P, Chretien S, Peres C, Tonks N, Roche S, Payrastre B, Chap H, Raynal P. A critical role for phosphoinositide 3-kinase upstream of Gab1 and SHP2 in the activation of ras and mitogen-activated protein kinases by epidermal growth factor. J Biol Chem. 2001 Mar 23;276(12):8856-64. doi: 10.1074/jbc.M006966200. Epub 2000 Dec 27.
Results Reference
background
PubMed Identifier
12024020
Citation
Zhang SQ, Tsiaras WG, Araki T, Wen G, Minichiello L, Klein R, Neel BG. Receptor-specific regulation of phosphatidylinositol 3'-kinase activation by the protein tyrosine phosphatase Shp2. Mol Cell Biol. 2002 Jun;22(12):4062-72. doi: 10.1128/MCB.22.12.4062-4072.2002.
Results Reference
background
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Study of Metabolic Modifications in Children With Noonan Syndrome
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