Growth Retardation In Children With Special Pathological Conditions Or Disease

Study Overview
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Brief Summary
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To show an increase in annual growth rate 3 years after Visit 2. Annual growth rate in standard deviation (SD) after 3 years will be compared to growth rate before the start of GH treatment.

Official Title
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Evolution Of Growth Rate In Children Suffering From A Disease Associated With Growth Retardation and Treated By Genotonorm. A Pilot Study.

Conditions
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Endocrine System Diseases

Intervention / Treatment
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* Drug: Somatropin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Bone age < 13 years for a boy and < 11 years for a girl Naive child: Measured Height < -2.5 SD for CA Child currently treated by GH Exclusion Criteria: Idiopathic short stature Syndrome known to be associated with an increased risk of cancer e.g. family history of adenomatous polyposis

Ages Eligible for Study
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Minimum Age: 11 Years
Maximum Age: 13 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: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Somatropin<br> | Drug: Somatropin<br>* Adapted dosage based on IGF 1 level and weight Form: liquid; Dosage and Frequency: from 0.0033mg/kg/day to 0.0067 mg/kg/day; Duration: 3 years<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 Standard Deviation Score (SDS) for Chronological Age (CA) at Month 36 in Intent-to-Treat (ITT) Population | Change in annual growth rate (AGR) standard deviation score (SDS) for chronological age (CA) derived by subtracting AGR SDS CA at baseline from each time point (Yx) value. AGR at Yx= (height Yx-height Y[x-1])/([date of Yx-date of Y{x-1}]/365.25). AGR as SDS calculated using Sempe reference means and standard deviations (SD) for growth rate. AGR SDS CA (for both baseline and Yx)= (AGR-reference mean for growth rate CA)/reference SD for growth rate CA. CA calculated as integer (Date of height measurement-Date of birth)/365.25*12. SDS indicates how similar participant was to reference population. | Baseline, Month 36 | 
| Change From Baseline in Annual Growth Rate Standard Deviation Score (SDS) for Chronological Age (CA) at Month 36 in Per-Protocol (PP) Population | Change in annual growth rate (AGR) standard deviation score (SDS) for chronological age (CA) derived by subtracting AGR SDS CA at baseline from each time point (Yx) value. AGR at Yx= (height Yx-height Y[x-1])/([date of Yx-date of Y{x-1}]/365.25). AGR as SDS calculated using Sempe reference means and standard deviations (SD) for growth rate. AGR SDS CA (for both baseline and Yx)= (AGR-reference mean for growth rate CA)/reference SD for growth rate CA. CA calculated as integer (Date of height measurement-Date of birth)/365.25*12. SDS indicates how similar participant was to reference population. | Baseline, Month 36 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Annual Growth Rate at Month 12, Month 24 and Month 36 in ITT Population | Change in AGR at Yx was derived by subtracting AGR at baseline from Yx value. Annual growth rate was calculated each year and rescaled to 1 year if the interval between Yx and Y[x-1] was not 365 days, as long as a participant remained in the study. AGR at Yx was calculated using the previous height measurements (Y[x-1]) and height recorded at Yx (AGR Yx = [height Yx-height Y{x-1}] / ([date of Yx - date of Y{x-1}] /365.25). | Baseline, Month 12, Month 24, Month 36 | 
| Change From Baseline in Annual Growth Rate at Month 12, Month 24, Month 36 in PP Population | Change in AGR at Yx was derived by subtracting AGR at baseline from Yx value. Annual growth rate was calculated each year and rescaled to 1 year if the interval between Yx and Y[x-1] was not 365 days, as long as a participant remained in the study. AGR at Yx was calculated using the previous height measurements (Y[x-1]) and height recorded at Yx (AGR Yx = [height Yx-height Y{x-1}] / ([date of Yx - date of Y{x-1}] /365.25). | Baseline, Month 12, Month 24, Month 36 | 
| Height | Height was measured using a wall mounted device (example, Harpenden stadiometer). The standing height of the participant was measured two times and the mean of these measurements was recorded. | Baseline, Month 12, Month 24, Month 36 | 
| Change From Baseline in Height at Month 12, Month 24 and Month 36 | Height was measured using a wall mounted device (example, Harpenden stadiometer). The standing height of the participant was measured two times and the mean of these measurements was recorded. | Baseline, Month 12, Month 24, Month 36 | 
| Mean Height Standard Deviation Score (SDS) for Chronological Age (CA) | Height was measured using a wall mounted device (example, Harpenden stadiometer). The standing height of the participant was measured two times and the mean of these measurements was recorded. Height SDS CA Yx = (height Yx - reference mean for CA Yx) / reference SD for CA Yx. Height in SDS was calculated using Sempe reference means and SD for height. CA calculated as integer (Date of height measurement-Date of birth)/365.25*12. SDS indicates how similar the participant was to the reference population. | Baseline, Month 12, Month 24, Month 36 | 
| Change From Baseline in Height Standard Deviation Score (SDS) for Chronological Age (CA) at Month 12, Month 24 and Month 36 | Change in height SDS CA was derived by subtracting height SDS CA at baseline from Yx value. Height SDS CA (for both baseline and Yx) = (height - reference mean for CA)/reference SD for CA. Height in SDS was calculated using Sempe reference means and SD for height. CA calculated as integer (Date of height measurement - Date of birth)/365.25*12. SDS indicates how similar the participant was to the reference population. | Baseline, Month 12, Month 24, Month 36 | 
| Mean Height Standard Deviation Score (SDS) for Bone Age (BA) | Height SDS BA Yx = (height Yx - reference mean for BA Yx) / reference SD for BA Yx. Height in SDS was calculated using Sempe reference means and SD for height. BA was estimated locally using an X-ray from the left wrist and hand. SDS indicates how similar the participant was to the reference population. | Baseline, Month 12, Month 24, Month 36 | 
| Change From Baseline in Height Standard Deviation Score (SDS) for Bone Age (BA) at Month 12, Month 24 and Month 36 | Change in height SDS BA was derived by subtracting height SDS BA at baseline from Yx value. Height SDS BA (for both baseline and Yx) = (height-reference mean for BA)/reference SD for BA. Height in SDS was calculated using Sempe reference means and SD for height. BA was estimated locally using an X-ray from the left wrist and hand. SDS indicates how similar the participant was to the reference population. | Baseline, Month 12, Month 24, Month 36 | 
| Change From Baseline in Annual Growth Rate Standard Deviation Score (SDS) for Chronological Age (CA) at Month 12 and Month 24 in ITT Population | Change in AGR SDS for CA derived by subtracting AGR SDS CA at baseline from Yx value. AGR at Yx= (height Yx-height Y[x-1])/([date of Yx-date of Y{x-1}]/365.25). AGR as SDS calculated using Sempe reference means and standard deviations (SD) for growth rate. AGR SDS CA (for both baseline and Yx)= (AGR-reference mean for growth rate CA)/reference SD for growth rate CA. CA calculated as integer (Date of height measurement-Date of birth)/365.25*12. SDS indicates how similar participant was to reference population. | Baseline, Month 12, Month 24 | 
| Change From Baseline in Annual Growth Rate Standard Deviation Score (SDS) for Chronological Age (CA) at Month 12 and Month 24 in PP Population | Change in annual growth rate (AGR) standard deviation score (SDS) for chronological age (CA) derived by subtracting AGR SDS CA at baseline from each time point (Yx) value. AGR at Yx= (height Yx-height Y[x-1])/([date of Yx-date of Y{x-1}]/365.25). AGR as SDS calculated using Sempe reference means and standard deviations (SD) for growth rate. AGR SDS CA (for both baseline and Yx)= (AGR-reference mean for growth rate CA)/reference SD for growth rate CA. CA calculated as integer (Date of height measurement-Date of birth)/365.25*12. SDS indicates how similar participant was to reference population. | Baseline, Month 12, Month 24 | 
| Mean Growth Rate Standard Deviation Score (SDS) for Bone Age (BA) | AGR at Yx was derived by subtracting AGR at baseline from Yx value. AGR was calculated each year and rescaled to 1 year if the interval between Yx and Y[x-1] was not 365 days, as long as a participant remained in the study. AGR at Yx = [height Yx-height Y{x-1}] / ([date of Yx - date of Y{x-1}] /365.25). GR in SDS was calculated using Sempe reference means and SD for growth. BA was estimated locally using an X-ray from the left wrist and hand. SDS indicates how similar the participant was to the reference population. | Month 12, Month 24, Month 36 | 
| Body Mass Index (BMI) | BMI was used to measure body fat based on height and weight. It was calculated as body weight (kilogram) divided by the height (meter) squared. | Baseline, Month 12, Month 24, Month 36 | 
| Change From Baseline in Body Mass Index (BMI) at Month 12, Month 24 and Month 36 | BMI was used to measure body fat based on height and weight. It was calculated as body weight (kilogram) divided by the height (meter) squared. | Baseline, Month 12, Month 24, Month 36 | 
| Change From Baseline in Bone Age (BA) at Month 12, Month 24 and Month 36 | BA was estimated locally using an X-ray from the left wrist and hand. | Baseline, Month 12, Month 24, Month 36 | 
| Ratio of Bone Age (BA) to Chronological Age (CA) | BA was estimated locally using an X-ray from the left wrist and hand. CA at the date of corresponding X-ray (Date of X-ray - Date of birth)/365.25. Ratio of BA/CA at each annual study visit was calculated. | Baseline, Month 12, Month 24, Month 36 |