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Study of Metabolic Modifications in Children With Noonan Syndrome (MetabNoonan)

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ClinicalTrials.gov Identifier: NCT02383316
Recruitment Status : Completed
First Posted : March 9, 2015
Last Update Posted : February 6, 2018
Sponsor:
Information provided by (Responsible Party):
University Hospital, Toulouse

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.

Condition or disease Intervention/treatment Phase
Child Syndrome Other: Oral Glucose tolerance test Not Applicable

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.


Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 20 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: Study of Metabolic Modifications in Children With Noonan Syndrome
Study Start Date : January 2015
Actual Primary Completion Date : June 2016
Actual Study Completion Date : June 2016


Arm Intervention/treatment
Experimental: Noonan Syndrome Children

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
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 Measures :
  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 Outcome Measures :
  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.



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Ages Eligible for Study:   7 Years to 18 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02383316


Locations
France
CHU Toulouse - Hôpital des Enfants
Toulouse, France, 31052
Sponsors and Collaborators
University Hospital, Toulouse
Investigators
Principal Investigator: Thomas Edouard, MD CHU Toulouse, Hôpital des Enfants

Publications:
Responsible Party: University Hospital, Toulouse
ClinicalTrials.gov Identifier: NCT02383316     History of Changes
Other Study ID Numbers: RC31/14/7315
AOL ( Other Grant/Funding Number: University Hospital Toulouse, local funding 2014 )
First Posted: March 9, 2015    Key Record Dates
Last Update Posted: February 6, 2018
Last Verified: February 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by University Hospital, Toulouse:
Insulin sensitivity
Metabolism
Noonan syndrome
Shp2

Additional relevant MeSH terms:
Syndrome
Noonan Syndrome
Disease
Pathologic Processes
Craniofacial Abnormalities
Musculoskeletal Abnormalities
Musculoskeletal Diseases
Heart Defects, Congenital
Cardiovascular Abnormalities
Cardiovascular Diseases
Heart Diseases
Congenital Abnormalities
Connective Tissue Diseases
Insulin
Hypoglycemic Agents
Physiological Effects of Drugs