French Registry of Children Treated With Norditropin® for Short Stature Associated With Noonan Syndrome

This is a non-interventional registry of children treated with Norditropin® for short stature due to Noonan Syndrome (NS). This study aims to provide data on long-term growth evolution and safety of Norditropin® as well as Health Related Quality of Life (HRQoL) data. This registry will include the entirety of children treated with Norditropin® for short stature due to NS over the inclusion period. The decision to initiate treatment with commercially available Norditropin® is made by the patient/parents/Legally Acceptable Representative (LAR) and the treating physician before and independently from the decision to include the patient in this study.

Study Overview

• Status: Enrolling by invitation
• Conditions: Noonan Syndrome
• Intervention / Treatment: Drug: Norditropin

• Study Type: Observational
• Enrollment (Estimated): 221

Contacts and Locations

Study Locations

• France
  • Angers, France, 49033
    • Centre Hospitalier Universitaire D'Angers-2
  • Le Kremlin-Bicêtre, France, 94275
    • Ap-Hp-Hopital de Bicetre-2
  • Toulouse, France, 31059
    • Hopital Des Enfants-2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

The registry will include children treated with Norditropin® for short stature due to NS.

Description

Inclusion Criteria:

• Patients with a clinical and/or genetic diagnosis of NS
• Patients who are treated with Norditropin® (already treated or initiating) and who are followed in a participating center
• The decision to initiate treatment with commercially available Norditropin® has been made by the patient/parents/Legally Acceptable Representative (LAR) and the treating physician before and independently from the decision to include the patient in this study

Exclusion Criteria:

• Patients/Parents/LAR opposed to the collection and processing of their children's medical data
• Mental incapacity, unwillingness or language barriers precluding adequate understanding or cooperation

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Other

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Incident patients; Children initiated Norditropin® upon their inclusion in the study but independently from the decision to participate in this study	Drug: Norditropin; Patients will be treated with commercially available Norditropin® according to routine clinical practice at the discretion of the treating physician.; Other Names: Somatropin
Prevalent patients - finished growth upon inclusion; Children were already treated with Norditropin® before their inclusion in the study and finished their growth upon their inclusion. Data collected retrospectively from medical records	Drug: Norditropin; Patients will be treated with commercially available Norditropin® according to routine clinical practice at the discretion of the treating physician.; Other Names: Somatropin
Prevalent patients - not finished growth upon inclusion; Children were already treated with Norditropin® before their inclusion in the study and did not finish their growth upon inclusion. Data collected both retrospectively and prospectively	Drug: Norditropin; Patients will be treated with commercially available Norditropin® according to routine clinical practice at the discretion of the treating physician.; Other Names: Somatropin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in height standard deviation score	Measured in standard deviation scores (SDS) ranging from -10 to +10	From start of Norditropin® treatment (day 0) until end of follow-up (up to 6 years)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of adverse drug reactions (ADR)	Count of events	From start of Norditropin® treatment (day 0) until end of follow-up (up to 6 years)
Number of serious adverse drug reactions (SADR)	Count of events	From start of Norditropin® treatment (day 0) until end of follow-up (up to 6 years)
Number of serious adverse events (SAE)	Count of events	From start of Norditropin® treatment (day 0) until end of follow-up (up to 6 years)
Number of adverse events (AE)	Count of events	From start of Norditropin® treatment (day 0) until end of follow-up (up to 6 years)
Education	Number of participants is measured under the categorical variables - standard education, education with assistance and educational measures	From start of Norditropin® treatment (day 0) until end of follow-up (up to 6 years)
School level	Number of participants is measured under the variables - preschool, elementary school, secondary school and high school	From start of Norditropin® treatment (day 0) until end of follow-up (up to 6 years)
Educational measures	Number of participants is measured under the categorical variables - physiotherapy, psychomotricity, occupational therapy and speech therapy	From start of Norditropin® treatment (day 0) until end of follow-up (up to 6 years)
Tanner stage	Measured as units on scale. 3 sub-scales used - Pubic hair scale, Female breast development scale and Male external genitalia scale. Tanner stages range from Stage 1 to 5 with Tanner Stage 1 corresponding to the pre-pubertal form and Tanner Stage 5 corresponding to the final adult form	From start of Norditropin® treatment (day 0) until end of follow-up (up to 6 years)
Change in pulse rate	Measured in beats per minute	From start of Norditropin® treatment (day 0) until end of follow-up (up to 6 years)
Change in diastolic blood pressure	Measured in millimeters of Mercury (mm Hg)	From start of Norditropin® treatment (day 0) until end of follow-up (up to 6 years)
Change in systolic blood pressure	Measured in mm Hg	From start of Norditropin® treatment (day 0) until end of follow-up (up to 6 years)
Change in corrected QT-interval (Electrocardiogram)	Measured in millisecond (msec)	From start of Norditropin® treatment (day 0) until end of follow-up (up to 6 years)
Change in echocardiogram parameters (mm)	Change in Left ventricular interventricular septal maximum thickness in diastole and Left ventricular end diastolic diameter is measured in millimeter (mm)	From start of Norditropin® treatment (day 0) until end of follow-up (up to 6 years)
Change in echocardiogram parameters (%)	Change in Left Ventricular Fractional Shortening (LVFS) and Left Ventricular Ejection Fraction (LVEF) is measured in percentage (%)	From start of Norditropin® treatment (day 0) until end of follow-up (up to 6 years)
Change in echocardiogram parameters (cm/s)	Change in Diastolic function (Ea and Aa) measured in centimeters per second (cm/s)	From start of Norditropin® treatment (day 0) until end of follow-up (up to 6 years)
Change in complete blood count (CBC) (g/dL)	Change in Haemoglobin (Hb) measured in grams per deciLiter (g/dL)	From start of Norditropin® treatment (day 0) until end of follow-up (up to 6 years)
Change in CBC (G/L)	Change in white blood cells, lymphocytes, monocytes and platelets measured in grams per liter (G/L)	From start of Norditropin® treatment (day 0) until end of follow-up (up to 6 years)
Change in Insulin-like growth factor 1 (IGF-1) level (ng/ml)	Measured in nanograms per milliliter (ng/ml)	From start of Norditropin® treatment (day 0) until end of follow-up (up to 6 years)
Change in IGF-1 level (SDS)	Measured in SDS	From start of Norditropin® treatment (day 0) until end of follow-up (up to 6 years)
Change in Haemoglobin A1c (HbA1c) level	Measured in %	From start of Norditropin® treatment (day 0) until end of follow-up (up to 6 years)
Change in fasting insulin level	Measured in milligrams per deciliter (mg/dL) or milli-international units per litre (mUI/L)	From start of Norditropin® treatment (day 0) until end of follow-up (up to 6 years)
Change in fasting blood glucose level	Measured in mg/dL or g/L or millimoles per litre (mmol/L)	From start of Norditropin® treatment (day 0) until end of follow-up (up to 6 years)
Change in fasting total cholesterol	Measured in mg/dl or g/L or mmol/L	From start of Norditropin® treatment (day 0) until end of follow-up (up to 6 years)
Change in fasting triglycerides	Measured in mg/dL or g/L or mmol/L	From start of Norditropin® treatment (day 0) until end of follow-up (up to 6 years)
Change in fasting high-density lipoproteins (HDL) cholesterol	Measured in mg/dL or g/L or mmol/L	From start of Norditropin® treatment (day 0) until end of follow-up (up to 6 years)
Change in fasting low-density lipoproteins (LDL) cholesterol	Measured in mg/dL or g/L or mmol/L	From start of Norditropin® treatment (day 0) until end of follow-up (up to 6 years)
Change in fasting total cholesterol/HDL ratio	Ratio of fasting total cholesterol and HDL	From start of Norditropin® treatment (day 0) until end of follow-up (up to 6 years)
Change in inhibin B	Measured in picograms per milliliter (pg/mL)	From start of Norditropin® treatment (day 0) until end of follow-up (up to 6 years)
Change in Anti-Müllerian Hormone (AMH)	Measured in milligrams per milliliter (mg/mL)	From start of Norditropin® treatment (day 0) until end of follow-up (up to 6 years)
Change in Luteinizing Hormone (LH) (female from 8 years old and male from 9 years old)	Measured in mg/mL	From start of Norditropin® treatment (day 0) until end of follow-up (up to 6 years)
Change in Follicle-Stimulating Hormone (FSH) (female from 8 years old and male from 9 years old)	Measured in International units per litre (UI/L) or mUI/mL	From start of Norditropin® treatment (day 0) until end of follow-up (up to 6 years)
Change in oestradiol (female from 8 years old and male from 9 years old)	Measured in pg/mL	From start of Norditropin® treatment (day 0) until end of follow-up (up to 6 years)
Change in testosterone (female from 8 years old and male from 9 years old)	Measured in ng/mL	From start of Norditropin® treatment (day 0) until end of follow-up (up to 6 years)
Change in dose of Norditropin® treatment	Measured in milligram per kilogram per day (mg/kg/day)	From start of Norditropin® treatment (day 0) until end of follow-up (up to 6 years)
Frequency of injections of Norditropin® treatment per week	Count of events	From start of Norditropin® treatment (day 0) until end of follow-up (up to 6 years)
Number of modifications (change in dosage/ temporary stop)	Count of events	From start of Norditropin® treatment (day 0) until end of follow-up (up to 6 years)
Reasons for treatment modifications	Measured in number of participants under categorical variable - safety (occurrence of ARs or AEs), growth too fast, growth too slow, patient's or parents/LAR choice; and other	From start of Norditropin® treatment (day 0) until end of follow-up (up to 6 years)
Duration of temporary stop	Measured in months	From start of Norditropin® treatment (day 0) until end of follow-up (up to 6 years)
Total duration of Norditropin® treatment	Measured in years	From start of Norditropin® treatment (day 0) until end of follow-up (up to 6 years)
Total cumulative dose of Norditropin® treatment	Measured in mg/kg	From start of Norditropin® treatment (day 0) until end of follow-up (up to 6 years)
Type and number of concomitant treatments	Count of events	From start of Norditropin® treatment (day 0) until end of follow-up (up to 6 years)
Type and number of concomitant treatments linked to an adverse event	Count of events	From start of Norditropin® treatment (day 0) until end of follow-up (up to 6 years)
Change in weight	Measured in SDS	From start of Norditropin® treatment (day 0) until end of follow-up (up to 6 years)
Change in body mass index (BMI)	Measured in kilogram per square metre (kg/m^2)	From start of Norditropin® treatment (day 0) until end of follow-up (up to 6 years)
Change in bone age	Measured in year	From start of Norditropin® treatment (day 0) until end of follow-up (up to 6 years)
Change in height velocity (cm/year)	Measured in cm/year	From start of Norditropin® treatment (day 0) until end of follow-up (up to 6 years)
Change in height velocity (SDS/year)	Measured in SDS/year	From start of Norditropin® treatment (day 0) until end of follow-up (up to 6 years)
Type and number of NS comorbidities	Number of participants measured under categorical variables - Cardiac defects including pulmonary valve stenosis and hypertrophic cardiomyopathy, Orthopaedic issues (pectus, scoliosis) and Anorchia in males	From start of Norditropin® treatment (day 0) until end of follow-up (up to 6 years)
Change in Health-Related Quality of Life (HRQoL) score (PedsQL)	PedsQL score used to assess the HRQoL, ranges from 1 to 100 (higher scores indicate better HRQoL)	From start of Norditropin® treatment (day 0) until end of follow-up (up to 6 years)

Collaborators and Investigators

• Sponsor: Novo Nordisk A/S
• Investigators: Study Director: Clinical Transparency dept. 2834, Novo Nordisk A/S

Study record dates

Study Major Dates

• Study Start (Actual): March 16, 2022
• Primary Completion (Estimated): March 17, 2028
• Study Completion (Estimated): March 17, 2028

Study Registration Dates

• First Submitted: March 14, 2022
• First Submitted That Met QC Criteria: March 24, 2022
• First Posted (Actual): April 4, 2022

Study Record Updates

• Last Update Posted (Estimated): September 25, 2025
• Last Update Submitted That Met QC Criteria: September 24, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Cardiovascular Diseases; Heart Diseases; Connective Tissue Diseases; Craniofacial Abnormalities; Musculoskeletal Abnormalities; Congenital Abnormalities; Cardiovascular Abnormalities; Heart Defects, Congenital; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Skin and Connective Tissue Diseases; Noonan Syndrome; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptide Hormones; Peptides; Amino Acids, Peptides, and Proteins; Pituitary Hormones; Growth Hormone; Pituitary Hormones, Anterior; Human Growth Hormone
• Other Study ID Numbers: GH-4831; U1111-1264-1805 (Other Identifier: World Health Organization (WHO))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: According to the Novo Nordisk disclosure commitment on novonordisk-trials.com

Drug and device information, study documents

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