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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

Tracking Information
First Submitted Date  ICMJE December 23, 2014
First Posted Date  ICMJE March 9, 2015
Last Update Posted Date February 6, 2018
Study Start Date  ICMJE January 2015
Actual Primary Completion Date June 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 2, 2015)
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
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02383316 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: August 16, 2016)
  • 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)
  • 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.
  • 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.
  • 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.
  • Body mass index [ Time Frame: T0 ]
    This test will be realised during hospitalisation day, at patient arrival.
  • Waist circumference [ Time Frame: T0 ]
    This test will be realised during hospitalisation day, at patient arrival.
  • Blood level of leptin [ Time Frame: T0 on an empty stomach ]
    Blood sample realised at T0 before the oral glucose tolerance test.
  • Blood level of ghrelin [ Time Frame: T0 on an empty stomach ]
    Blood sample realised at T0 before the oral glucose tolerance test.
Original Secondary Outcome Measures  ICMJE
 (submitted: March 2, 2015)
  • 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 mesured 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 [ 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.
  • 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.
  • 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.
  • Body mass index [ Time Frame: T0 ]
    This test will be realised during hospitalisation day, at patient arrival.
  • Waist circumference [ Time Frame: T0 ]
    This test will be realised during hospitalisation day, at patient arrival.
  • Blood level of leptin [ Time Frame: T0 on an empty stomach ]
    Blood sample realised at T0 before the oral glucose tolerance test.
  • Blood level of ghrelin [ Time Frame: T0 on an empty stomach ]
    Blood sample realised at T0 before the oral glucose tolerance test.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of Metabolic Modifications in Children With Noonan Syndrome
Official Title  ICMJE Study of Metabolic Modifications in Children With Noonan Syndrome
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Condition  ICMJE Child Syndrome
Intervention  ICMJE 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.
Study Arms  ICMJE 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).

Intervention: Other: Oral Glucose tolerance test
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: March 2, 2015)
20
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE June 2016
Actual Primary Completion Date June 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 7 Years to 18 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE France
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02383316
Other Study ID Numbers  ICMJE RC31/14/7315
AOL ( Other Grant/Funding Number: University Hospital Toulouse, local funding 2014 )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party University Hospital, Toulouse
Study Sponsor  ICMJE University Hospital, Toulouse
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Thomas Edouard, MD CHU Toulouse, Hôpital des Enfants
PRS Account University Hospital, Toulouse
Verification Date February 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP