Treatment With Recombinant Human Growth Hormone (GH) in Children With Short Stature Secondary to a Long Term Corticoid Therapy

Study Overview
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Brief Summary
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To assess the effect of a long-term treatment by Genotonorm on linear growth in children with short stature receiving steroid therapy To assess the effect of a long term treatment with Genotonorm on bone mineralisation To assess the effect of a long term treatment with Genotonorm on body composition

Detailed Description
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This trial terminated on 10-Jun-2011 due to prolonged issues with drug accountability and data collection discrepancies. The decision to terminate was not based on any safety concerns.

Official Title
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Treatment With Recombinant Human Growth Hormone Genotonorm (Registered) in Children With Short Stature Secondary to a Long Term Corticoid Therapy. A Study of Efficacy and Safety.

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: Children with juvenile arthritis or nephrotic syndrome Before or during puberty Exclusion Criteria: Diabetes Type 1 and 2 Endocrine disease, except well substituted hypothyroidism

Ages Eligible for Study
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Minimum Age: 11 Years
Maximum Age: 17 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>* liquid, daily, until final height Dosage: 0,46 mg/kg/week . The maximum dose should not exceed 50 µg/Kg/day<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Height Standard Deviation Score According to Chronological Age (SDS/CA) at Year 3 | Height was measured using a wall mounted device (example, Harpenden stadiometer). Height SDS/CA was obtained by measuring the height, subtracting chronological age- and gender-appropriate mean height and dividing the result by standard deviation of that mean (as obtained from chronological age- and gender-specific population reference data). SDS indicated how many standard deviations higher (in case of positive SDS) or lower (in case of negative SDS) participant's value was relative to the mean of the reference population. | Baseline, Year 3 | 
| Change From Baseline in Height Standard Deviation Score According to Chronological Age (SDS/CA) at Final Height | Height was measured using a wall mounted device (example, Harpenden stadiometer). Height SDS/CA was obtained by measuring the height, subtracting chronological age- and gender-appropriate mean height and dividing the result by standard deviation of that mean (as obtained from chronological age- and gender-specific population reference data). SDS indicated how many standard deviations higher (in case of positive SDS) or lower (in case of negative SDS) participant's value was relative to the mean of the reference population. | Baseline, when final height was reached (assessed up to Year 11) | 
| Change From Baseline in Weight Standard Deviation Score (SDS) at Final Height | Body weight was measured using a balance scale. Weight SDS was obtained by measuring the weight, subtracting age- and gender-appropriate mean weight and dividing the result by standard deviation of that mean (as obtained from age- and gender-specific population reference data). SDS indicated how many standard deviations higher (in case of positive SDS) or lower (in case of negative SDS) participant's value was relative to the mean of the reference population. | Baseline, when final height was reached (assessed up to Year 11) | 
| Puberty Stage at Final Height | Pubertal stage (graded from I to V for breast development and pubic hair development) according to the Tanner's method was collected. A low stage (Stage I) corresponds to a pre-pubertal stage and a high stage (Stage V) to an adult stage. | When final height was reached (assessed up to Year 11) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Bone Age | Bone age was determined by the Greulich and Pyle method using left wrist and hand X-ray. | Baseline, Year 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 | 
| Lean Body Mass | Lean body mass, a measurement of body composition, was assessed by Dual Energy X-ray Absorptiometry (DEXA) scan. | Baseline, Year 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 | 
| Annual Percent Change in Lean Body Mass at Year 1, 2 and 3 | Lean body mass, a measurement of body composition, was assessed by DEXA scan. Annual percent change: (Lean body mass at current year minus lean body mass at previous year) divided by lean body mass at previous year, multiplied by 100. | Baseline, Year 1, 2, 3 | 
| Percent Change From Baseline in Lean Body Mass at Year 3 | Lean body mass, a measurement of body composition, was assessed by DEXA scan. Percent change: (Lean body mass at Year 3 minus lean body mass at baseline) divided by lean body mass at baseline, multiplied by 100. | Baseline, Year 3 | 
| Lean Body Mass as Percentage of Total Weight | Lean body mass, a measurement of body composition, was assessed by DEXA scan. | Baseline, Year 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 | 
| Lean Body Mass Standard Deviation Score According to Chronological Age (SDS/CA) | Lean body mass was assessed by DEXA scan. Lean body mass SDS/CA was obtained by measuring lean body mass, subtracting the chronological age- and gender-appropriate mean lean body mass and dividing the result by standard deviation of that mean (as obtained from chronological age- and gender-specific population reference data). SDS indicated how many standard deviations higher (in case of positive SDS) or lower (in case of negative SDS) participant's value was relative to the mean of the reference population. | Baseline, Year 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 | 
| Fat Mass | Fat mass, a measurement of body composition, was assessed by DEXA scan. | Baseline, Year 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 | 
| Annual Percent Change in Fat Mass at Year 1, 2 and 3 | Fat mass, a measurement of body composition, was assessed by DEXA scan. Annual percent change: (Fat mass at current year minus fat mass at previous year) divided by fat mass at previous year, multiplied by 100. | Baseline, Year 1, 2, 3 | 
| Percent Change From Baseline in Fat Mass at Year 3 | Fat mass, a measurement of body composition, was assessed by DEXA scan. Percent change: (Fat mass at Year 3 minus fat mass at baseline) divided by fat mass at baseline, multiplied by 100. | Baseline, Year 3 | 
| Fat Mass as Percentage of Total Weight | Fat mass, a measurement of body composition, was assessed by DEXA scan. | Baseline, Year 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 | 
| Fat Mass Standard Deviation Score According to Chronological Age (SDS/CA) | Fat mass was assessed by DEXA scan. Fat mass SDS/CA was obtained by measuring fat mass, subtracting chronological age- and gender-appropriate mean fat mass and dividing the result by standard deviation of that mean (as obtained from chronological age- and gender-specific population reference data). SDS indicated how many standard deviations higher (in case of positive SDS) or lower (in case of negative SDS) participant's value was relative to the mean of the reference population. | Baseline, Year 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 | 
| Apparent Bone Mineral Density of Lumbar Spine (BMAD [LS]) | BMAD (LS) was assessed by DEXA scan. | Baseline, Year 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 | 
| Apparent Bone Mineral Density Standard Deviation Score of Lumbar Spine According to Chronological Age (BMAD [LS] [SDS/CA]) | BMAD (LS) was assessed by DEXA scan. BMAD (LS) (SDS/CA) was obtained by measuring the BMAD (LS), subtracting chronological age- and gender-appropriate mean BMAD (LS) and dividing the result by standard deviation of that mean (as obtained from chronological age- and gender-specific population reference data). SDS indicated how many standard deviations higher (in case of positive SDS) or lower (in case of negative SDS) participant's value was relative to the mean of the reference population. | Baseline, Year 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 | 
| Apparent Bone Mineral Density Standard Deviation Score of Lumber Spine According to Tanner Puberty Stage (BMAD [LS] [SDS/Tanner Puberty Stage]) | BMAD (LS) was assessed by DEXA scan. BMAD (LS) (SDS/Tanner Puberty Stage) was obtained by measuring BMAD (LS), subtracting Tanner puberty stage- and gender-appropriate mean BMAD (LS) and dividing the result by standard deviation of that mean (as obtained from Tanner puberty stage- and gender-specific population reference data). SDS indicated how many standard deviations higher (in case of positive SDS) or lower (in case of negative SDS) participant's value was relative to the mean of the reference population. | Baseline, Year 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 | 
| Bone Mineral Density of Total Body (BMD [TB]) | BMD (TB) was assessed by DEXA scan. | Baseline, Year 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 | 
| Bone Mineral Density of Lumbar Spine (BMD [LS]) | BMD (LS) was assessed by DEXA scan. | Baseline, Year 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 | 
| Bone Mineral Content of Total Body (BMC [TB]) | DEXA scan of BMC was used to evaluate potential bone effects of treatment. BMC is an estimate of the amount of mineral (such as calcium) in the bone. | Baseline, Year 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 | 
| Annual Percent Change in Bone Mineral Content of Total Body (BMC [TB]) at Year 1, 2 and 3 | BMC is an estimate of the amount of mineral (such as calcium) in the bone. Annual percent change: (BMC [TB] at current year minus BMC [TB] at previous year) divided by BMC [TB] at previous year, multiplied by 100. | Baseline, Year 1, 2, 3 | 
| Percent Change From Baseline in Bone Mineral Content of Total Body (BMC [TB]) at Year 3 | BMC is an estimate of the amount of mineral (such as calcium) in the bone. Percent change: (BMC [TB] at Year 3 minus BMC [TB] at baseline) divided by BMC [TB] at baseline, multiplied by 100. | Baseline, Year 3 | 
| Bone Mineral Content Standard Deviation Score of Total Body According to Chronological Age (BMC [TB] [SDS/CA]) | BMC (TB) was measured by DEXA scan. BMC (TB) (SDS/CA) was obtained by measuring BMC (TB), subtracting the chronological age- and gender-appropriate mean BMC (TB) and dividing the result by standard deviation of that mean (as obtained from chronological age- and gender-specific population reference data). SDS indicated how many standard deviations higher (in case of positive SDS) or lower (in case of negative SDS) participant's value was relative to the mean of the reference population. | Baseline, Year 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 | 
| Bone Mineral Content Standard Deviation Score of Total Body According to Tanner Puberty Stage (BMC [TB] [SDS/Tanner Puberty Stage]) | BMC (TB) was measured by DEXA scan. BMC (TB) (SDS/Tanner Puberty Stage) was obtained by measuring BMC (TB), subtracting the Tanner puberty stage- and gender-appropriate mean BMC (TB) and dividing the result by standard deviation of that mean (as obtained from Tanner puberty stage- and gender-specific population reference data). SDS indicated how many standard deviations higher (in case of positive SDS) or lower (in case of negative SDS) participant's value was relative to the mean of the reference population. | Baseline, Year 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 |