Genotropin Treatment in Short Prepubertal Children With Intra-Uterine Growth Retardation

Study Overview
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Brief Summary
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To evaluate the effect of continuous and intermittent administration of Genotonorm on stature in short prepubertal children with intra-uterine growth retardation

Official Title
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A Two Years Multicentre Study of Genotropin Treatment of Short Prepubertal Children With Intra-Uterine Growth Retardation

Conditions
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Growth Disorders, Intrauterine Growth Retardation

Intervention / Treatment
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* Drug: Genotonorm
* Drug: Genotonorm
* Drug: Genotonorm


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Chronological age (CA) between 3 and 10 for girls Chronological age between 3 and 12 for boys Height for CA below - 2 SD Birth length for CA below -2SD Exclusion Criteria: Endocrine disease except well-substituted hypothyroidism Sever chronic disease Skeletal dysplasia Known chromosomal aberration Ongoing treatment with steroids Known intrauterine infection

Ages Eligible for Study
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Minimum Age: 3 Years
Maximum Age: 12 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Genotonorm A<br>Continuous 0.7 IU/kg/week or 0.03 mg/kg/day | Drug: Genotonorm<br>* 0.7 IU/kg/week or 0.03 mg/kg/day, daily subcutaneous injection<br>|
| Active Comparator: Genotonorm B<br>Continuous, 1.4 IU/kg/week or 0.06 mg/kg/day | Drug: Genotonorm<br>* 1.4 IU/kg/week or 0.06 mg/kg/day, daily subcutaneous injection<br>|
| Active Comparator: Genotonorm C<br>Intermittent, 1.4 IU/kg/week or 0.06 mg/kg/day | Drug: Genotonorm<br>* 1.4 IU/kg/week or 0.06 mg/kg/day, daily subcutaneous injection Intermittent treatment (6 months with treatment and 6 months without)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Annual Growth Rate Measured at 2 Years Following Treatment With Genotonorm | Annual growth rate was expressed as height velocity (centimeter [cm]/year). This was derived by substracting annual growth rate at Baseline from 2-year value. (Annual growth rate was calculated each year and rescaled to 1 year if the interval between x and x-1 was not 365 days, as long as a subject remains in the study): ANGRYx = (Height Yx - Height Y{x-1}) / {(Date of Yx - Date of Y{x-1}) /365.25} | Baseline, 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Annual Growth Rate Standard Deviation Score (SDS) | Calculated using Sempe reference means and standard deviations for growth rate according to age and sex. Standardization was performed for chronological age. | Baseline, 1 to 6 years | 
| Change From Baseline in Annual Growth Rate SDS | Calculated corresponding to the gender and chronological age by substracting annual growth rate SDS at Baseline from annual growth rate SDS at each year. | Baseline, 1 to 3 years | 
| Height (cm) | Performed by use of a wallmounted device (eg, Harpenden Stadiometer). Each subject was measured 3 times and the mean of these measurements was recorded as the present height. Final Height: Children are defined as reaching their final height when annual Growth Rate is less than 2 cm in the previous year and bone age is equal to or greater than 17 years in boys and equal to or greater than 15 years in girls. | Baseline, 1 to 6 years, final height | 
| Change From Baseline in Height (cm) | Calculated by substracting height at Baseline from height at each year. Final Height: Children are defined as reaching their final height when annual Growth Rate is less than 2 cm in the previous year and bone age is equal to or greater than 17 years in boys and equal to or greater than 15 years in girls. | Baseline, 1 to 6 years, final height | 
| Height (SDS) | Calculated using Sempe reference means and standard deviations for height. Final Height: Children are defined as reaching their final height when annual Growth Rate is less than 2 cm in the previous year and bone age is equal to or greater than 17 years in boys and equal to or greater than 15 years in girls. | Baseline, 1 to 6 years, final height | 
| Change From Baseline in Height (SDS) | Calculated by substracting height SDS at Baseline from height SDS at each year. Final Height: Children are defined as reaching their final height when annual Growth Rate is less than 2 cm in the previous year and bone age is equal to or greater than 17 years in boys and equal to or greater than 15 years in girls. | Baseline, 1 to 6 years, final height | 
| Body Mass Index (BMI) | BMI was calculated by weight divided by height squared. | Baseline, 1 to 6 years | 
| Weight |  | Baseline, 1 to 6 years | 
| Change From Baseline in Bone Age | Bone age was determined by the Greulich-Pyle method. Calculated by substracting bone age at Baseline from bone age at each year | Baseline, 1 to 3 years | 
| Change From Baseline in Bone Age/Change From Baseline in Chronological Age Ratio | Bone age was determined by the Greulich-Pyle method. Chronological Age (years) was calculated as: (Date minus Date of Birth) divided by 365.25. Chronological Age used was the age at the date that the corresponding Bone Age X-ray was performed. Ratio was calculated by change from Baseline in bone age divided by change from Baseline in chronological age. | 1 to 3 years | 
| Chronological Age at Onset of Puberty | Chronological age (years) at first study visit with onset of puberty = (Date of study visit minus Date of Birth) divided by 365.25. | Onset of puberty | 
| Number of Subjects Reaching Puberty | The defined criteria for reaching puberty were: boy=if right or left testes volume ≥4 ml; girl=if breast development ≥2. Tanner Adolescent Pubertal Staging Questionnaire documents the stage of development of secondary sexual characteristics rated in 5 stages: stage 1 (no development) to 5 (adult-like development in quantity and size). Onset of puberty was defined as the visit where the data recorded first met the above criteria for starting puberty. | Baseline, 1 to 6 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Short height, intra-uterine growth retardation, Genotonorm, continuous treatment, intermittent treatment