Neuromuscular Changes In Small For Gestational Age Children During Somatropin Therapy

Phase 3

Terminated

Conditions: Infant, Small for Gestational Age
Growth Hormone Therapy

Interventions: Drug: Somatropin

Registration Number: NCT00625872

Lead Sponsor: Pfizer

Brief Summary: The planned study focuses on the effect of a one year Somatropin treatment (0.035 mg/kg/d or 0.067 mg/kg/d) in short children born SGA on neuromuscular function and cognitive performance.

Detailed Description: Not available

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 23

Inclusion Criteria

Pre-pubertal boys between 6 and 10 years of age or girls between 6 and 9 years of age.
Birth length- and/or birth weight-SDS adjusted to gestational age < -2.0 (Voigt et al. 2002, Voigt et al. 2006 or Lawrence et al. 1989).
Current height-SDS < -2.5 (Brandt/Reinken 1992) and parental adjusted height-SDS below -1 (Hermanussen and Cole 2003).
Growth velocity SDS < 0 during the last year before inclusion (Brandt/Reinken 1988).

Exclusion Criteria

Severe SGA (birth weight or length < -4 SD) and clinically relevant dysmorphic features.
Severe pre-maturity (GA < 32 weeks of gestation).
Severe perinatal complications like asphyxia, sepsis, necrotizing enterocolitis (NEC), respiratory distress syndrome, if associated with long-term sequelae (like short bowel syndrome, bronchopulmonary dysplasia (BPD), cerebral palsy etc).
Inability to perform one- or two leg jumps from a standing position.
Prior GH treatment.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Treatment Group	Somatropin	Somatropin for 12 months
Control Group	Somatropin	In the first 6 months no intervention, afterwards Somatropin for 12 months

Primary Outcome Measures

Name	Time	Method
Change From Baseline in Maximum Jump Velocity (Vmax; Two-leg-jump) in Per Protocol (PP) Population at Month 6	Baseline and Month 6	Vmax was measured by Leonardo Jumping Platform during two-leg jump.
Change From Baseline in Peak Jump Power Standard Deviation Score (PJP-SDS; Two-leg-jump) in Full Analysis Set (FAS) Population at Month 6	Baseline and Month 6	Peak jump power (PJP) was defined as the peak of the calculated power (force multiplied by velocity). It was measured by Leonardo Jumping Platform during two-leg jump. The participant performs 3 jumps and the highest peak (PJP) of the 3 recordings was selected for further calculations. The SDS indicates how similar the participant was to the reference population.
Change From Baseline in Peak Jump Force Standard Deviation Score (PJF-SDS; Two-leg-jump) in Per Protocol (PP) Population at Month 6	Baseline and Month 6	PJF was defined as the maximum of force of the ascending part of the jump which the participant performed as a counter-movement jump with freely moving arms and as high as possible with the head and chest. It was measured by Leonardo Jumping Platform during two-leg jump. The SDS indicates how similar the participant was to the reference population.
Change From Baseline in Peak Jump Power Standard Deviation Score (PJP-SDS; Two-leg-jump) in Per Protocol (PP) Population at Month 6	Baseline and Month 6	PJP was defined as the peak of the calculated power (force multiplied by velocity). It was measured by Leonardo Jumping Platform during two-leg jump. The participant performs 3 jumps and the highest peak (PJP) of the 3 recordings was selected for further calculations. The SDS indicates how similar the participant was to the reference population.
Change From Baseline in Maximum Jump Velocity (Vmax; Two-leg-jump) in Full Analysis Set (FAS) Population at Month 6	Baseline and Month 6	Vmax was measured by Leonardo Jumping Platform during two-leg jump.
Change From Baseline in Peak Jump Force Standard Deviation Score (PJF-SDS; Two-leg-jump) in Full Analysis Set (FAS) Population at Month 6	Baseline and Month 6	PJF was defined as the maximum of force of the ascending part of the jump which the participant performed as a counter-movement jump with freely moving arms and as high as possible with the head and chest. It was measured by Leonardo Jumping Platform during two-leg jump. The SDS indicates how similar the participant was to the reference population.

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in Intellectual Performance of Children Using Kinderversion Der Testbatterie Zur Aufmerksamkeitsprüfung für Kinder (KITAP) Test at Month 6	Baseline and Month 6	The KITAP is a computer aided standardized neuro-cognitive development test which allows examination of a wide range of attention and executive functions such as shift of attention (Distractibility); simple reaction time (Alertness); "Sustained Attention", change of reaction (Flexibility); "Divided Attention", controlled reaction disposition (Go/No go) and "Vigilance". It has been designed appropriately for children between the age of 6 to 10 years to allow optimal motivation during testing and to increase validity of results.
Change From Baseline in Peak Jump Power Standard Deviation Score (PJP-SDS; One-leg-jump) at Months 6, 12 and 18	Baseline, Month 6 , Month 12 and Month 18	PJP was defined as the peak of the calculated power (force multiplied by velocity). It was measured by Leonardo Jumping Platform during one leg jump. The participant performs 3 jumps and the highest peak (PJP) of the 3 recordings was selected for further calculations. The SDS indicates how similar the participant was to the reference population.
Change From Baseline in Peak Jump Force Standard Deviation Score (PJF-SDS; One-leg-jump) at Months 6, 12 and 18	Baseline, Month 6, Month 12 and Month 18	PJF was defined as the maximum of force of the ascending part of the jump which the participant performed as a counter-movement jump with freely moving arms and as high as possible with the head and chest. It was measured by Leonardo Jumping Platform during one leg jump. The SDS indicates how similar the participant was to the reference population.
Change From Baseline in Five-chair Rising Test- Peak Jump Power (PJP) at Month 6	Baseline and Month 6	The Chair rising test is a performance test (total power output) to measure neuromuscular function of complex movement in standing up. Test allows diagnostics of movement deficits using Leonardo jump plate. Five stand up test: five repetitions of rising from a chair on jump plate as quickly as possible with arms crossed over the chest (time to perform the tasks, maximal PJP, maximal velocity and maximal PJF). PJP is defined as the peak of the calculated power (force multiplied by velocity).
Change From Baseline in Five-chair Rising Test-Peak Jump Force (PJF) at Months 12 and 18	Baseline, Month 12 and Month 18	The Chair rising test is a performance test (total power output) to measure neuromuscular function of complex movement in standing up. Test allows diagnostics of movement deficits using Leonardo jump plate. Five stand up test: five repetitions of rising from a chair on jump plate as quickly as possible with arms crossed over the chest (time to perform the tasks, maximal PJP, maximal velocity and maximal PJF). PJF is the maximum force of the ascending part of the jump which the participant performed as a counter-movement jump with freely moving arms as high as possible with the head and chest.
Change From Baseline in Intellectual Performance of Children Using Kaufmann-Assessment Battery for Children (K-ABC) Test Global Scales at Months 12 and 18	Baseline, Month 12 and Month 18	K-ABC was assessed in children between 2.5-12.5 years. Comprised of 16 subtests; 10 mental processing (intelligence) and 6 achievement subtests. Achievement subtests: expressive vocabulary, faces\&places, arithmetic, riddles, reading/decoding, reading/comprehension. Sixteen subtests were weighted accordingly to form 5 global scales: sequential processing, simultaneous processing, achievement, non-verbal and mental processing composite. Scores were rated as upper extreme \[greater than (\>) 131\], above average (116-130), average (85-115), below average (70-84), lower extreme \[less than (\<) 69\].
Change From Baseline in Intellectual Performance of Children Using Child Behavior Checklist 4-18 Years (CBCL 4-18) at Months 6, 12 and 18	Baseline, Month 6, Month 12 and Month 18	CBCL was standardized for children ages 4 to 18 years and measured child internalizing and externalizing behaviors and total problems. The 4-18 years' checklist contains 140 questions and responses were recorded on a Likert scale: 0 = Not True, 1 = Somewhat or Sometimes True, 2 = Very True or Often True. The range of possible values was 0-280 (0=good to 280=worst).
Change From Baseline in Five-chair Rising Test-Peak Jump Power (PJP) at Months 12 and 18	Baseline, Month 12 and Month 18	The Chair rising test is a performance test (total power output) to measure neuromuscular function of complex movement in standing up. Test allows diagnostics of movement deficits using Leonardo jump plate. Five stand up test: five repetitions of rising from a chair on jump plate as quickly as possible with arms crossed over the chest (time to perform the tasks, maximal PJP, maximal velocity and maximal PJF). PJP is defined as the peak of the calculated power (force multiplied by velocity).
Change From Baseline in Five-chair Rising Test-Peak Jump Force (PJF) at Month 6	Baseline and Month 6	The Chair rising test is a performance test (total power output) to measure neuromuscular function of complex movement in standing up. Test allows diagnostics of movement deficits using Leonardo jump plate. Five stand up test: five repetitions of rising from a chair on jump plate as quickly as possible with arms crossed over the chest (time to perform the tasks, maximal PJP, maximal velocity and maximal PJF). PJF is the maximum force of the ascending part of the jump which the participant performed as a counter-movement jump with freely moving arms as high as possible with the head and chest.
Change From Baseline in One-chair Rising Test-Peak Jump Power (PJP) at Months 6, 12 and 18	Baseline, Month 6 , Month 12 and Month 18	The Chair rising test is a performance test (total power output) to measure neuromuscular function of complex movement to stand up. Test allows diagnostics of movement deficits using Leonardo jump plate. One stand up test: rising from a chair on the jump plate as quickly as possible with arms crossed over the chest (analysis of time, PJP, PJF and time of fastest rising). PJP is defined as the peak of the calculated power (force multiplied by velocity).
Mean Thigh Circumference	Baseline, Month 6, Month 12 and Month 18	Thigh measurements were taken as a mean of 3 consecutive measurements at upper thigh about an inch down from the crotch line.
Mean Height at Month 6	Month 6	Standing height was taken as a mean of 3 consecutive measurements using a wall mounted stadiometer.
Change From Baseline in Intellectual Performance of Children Using Non-verbal Learning Test (NVLT) at Months 12 and 18	Baseline, Month 12 and Month 18	NVLT was assessed for visual memorization that was difficult to verbalize. Test recorded instability index, T-scores\[sum of differences of correct {C} - incorrect {IC} "Yes" answers(1);sum of C "Yes" answers(2);sum of IC "Yes" answers(3);sum of differences of C-IC "Yes" answers with high associative items{ 87%-95%}(4);sum of differences of C-IC "Yes" answers with low associative items{ 54%-64%}(5); difference between difference values for high and low associative items(6)\].Scores were rated as below average(\<40), average(40-60), above average(\>60) and working time ranging between 9-12 minutes.
Change From Baseline in Maximum Jump Velocity (Vmax; One-leg-jump) at Months 6, 12 and 18	Baseline, Month 6, Month 12 and Month 18	Vmax was measured by Leonardo Jumping Platform during one leg jump.
Mean Growth Velocity at Months 12 and 18	Month 12 and Month 18	Growth velocity measures the annual rate of increase in height.
Mean Height-Standard Deviation Score (SDS) at Month 6	Month 6	Standing height was taken as a mean of 3 consecutive measurements using a wall mounted stadiometer. The SDS indicates how similar the participant was to the reference population.
Change From Baseline in Intellectual Performance of Children Using Kaufmann-Assessment Battery for Children (K-ABC) Test Global Scales at Month 6	Baseline and Month 6	K-ABC was assessed in children between 2.5-12.5 years. Comprised of 16 subtests; 10 mental processing (intelligence) and 6 achievement subtests. Achievement subtests: expressive vocabulary, faces\&places, arithmetic, riddles, reading/decoding, reading/comprehension. Sixteen subtests were weighted accordingly to form 5 global scales: sequential processing, simultaneous processing, achievement, non-verbal and mental processing composite. Scores were rated as upper extreme \[greater than (\>) 131\], above average (116-130), average (85-115), below average (70-84), lower extreme \[less than (\<) 69\].
Change From Baseline in Intellectual Performance of Children Using Non-verbal Learning Test (NVLT) at Month 6	Baseline and Month 6	NVLT was assessed for visual memorization that was difficult to verbalize. Test recorded instability index, T-scores\[sum of differences of correct {C} - incorrect {IC} "Yes" answers(1);sum of C "Yes" answers(2);sum of IC "Yes" answers(3);sum of differences of C-IC "Yes" answers with high associative items{ 87%-95%}(4);sum of differences of C-IC "Yes" answers with low associative items{ 54%-64%}(5); difference between difference values for high and low associative items(6)\].Scores were rated as below average(\<40), average(40-60), above average(\>60) and working time ranging between 9-12 minutes.
Change From Baseline in Five-chair Rising Test-Maximum Jump Velocity (Vmax) at Month 6	Baseline and Month 6	The Chair rising test is a performance test (total power output) to measure neuromuscular function of complex movement in standing up. Test allows diagnostics of movement deficits using Leonardo jump plate. Five stand up test: five repetitions of rising from a chair on jump plate as quickly as possible with arms crossed over the chest (time to perform the tasks, maximal PJP, maximal velocity and maximal PJF). Vmax is defined as the maximum jump velocity.
Change From Baseline in Five-chair Rising Test (Time to Perform the Tasks) at Months 12 and 18	Baseline, Month 12 and Month 18	Chair rising test is performance test (total power output) to measure neuromuscular function of complex movement in standing up. Test allows diagnostics of movement deficits using Leonardo jump plate. Five stand up test: 5 repetitions of rising from a chair on jump plate as quickly as possible with arms crossed over chest (time to perform tasks, maximal PJP, maximal velocity and maximal PJF). Time to perform task includes: Average (avg) rise time which is avg time to perform 1 rise, avg time per test is the avg time to perform 1 test (rise and sitting down) and total time to perform 5 tests.
Change From Baseline in One-chair Rising Test-Peak Jump Force (PJF) at Months 6, 12 and 18	Baseline, Month 6 , Month 12 and Month 18	The Chair rising test is a performance test (total power output) to measure neuromuscular function of complex movement to stand up. Test allows diagnostics of movement deficits using Leonardo jump plate. One stand up test: rising from a chair on the jump plate as quickly as possible with arms crossed over the chest (analysis of time, PJP, PJF and time of fastest rising). PJF is the maximum force of the ascending part of the jump which the participant performed as a counter-movement jump with freely moving arms as high as possible with the head and chest.
Mean Growth Velocity at Month 6	Month 6	Growth velocity measures the annual rate of increase in height.
Mean Growth Velocity-Standard Deviation Score (SDS) at Month 6	Month 6	Growth velocity measures the annual rate of increase in height. The SDS indicates how similar the participant is to the reference population.
Mean Growth Velocity-Standard Deviation Score (SDS) at Months 12 and 18	Month 12 and Month 18
Change From Baseline in Intellectual Performance of Children Using Kinderversion Der Testbatterie Zur Aufmerksamkeitsprüfung für Kinder (KITAP) Test at Months 12 and 18	Baseline, Month 12 and Month 18	The KITAP is a computer aided standardized neuro-cognitive development test which allows examination of a wide range of attention and executive functions such as shift of attention (Distractibility); simple reaction time (Alertness); "Sustained Attention", change of reaction (Flexibility); "Divided Attention", controlled reaction disposition (Go/No go) and "Vigilance". It has been designed appropriately for children between the age of 6 to 10 years to allow optimal motivation during testing and to increase validity of results.
Change From Baseline in Five-chair Rising Test-Maximum Jump Velocity (Vmax) at Months 12 and 18	Baseline, Month 12 and Month 18	The Chair rising test is a performance test (total power output) to measure neuromuscular function of complex movement in standing up. Test allows diagnostics of movement deficits using Leonardo jump plate. Five stand up test: five repetitions of rising from a chair on jump plate as quickly as possible with arms crossed over the chest (time to perform the tasks, maximal PJP, maximal velocity and maximal PJF). Vmax is defined as the maximum jump velocity.
Change From Baseline in Five-chair Rising Test (Time to Perform the Tasks) at Month 6	Baseline and Month 6	Chair rising test is performance test (total power output) to measure neuromuscular function of complex movement in standing up. Test allows diagnostics of movement deficits using Leonardo jump plate. Five stand up test: 5 repetitions of rising from a chair on jump plate as quickly as possible with arms crossed over chest (time to perform tasks, maximal PJP, maximal velocity and maximal PJF). Time to perform task includes: Average (avg) rise time which is avg time to perform 1 rise, avg time per test is the avg time to perform 1 test (rise and sitting down) and total time to perform 5 tests.
Change From Baseline in Maximal Isometric Grip Force-Standard Deviation Score (MIGF-SDS) at Month 6	Baseline and Month 6	MIGF was assessed using standard adjustable Jamar dynamometer. MIGF (in Newtons) was calculated by multiplying the dynamometer reading (in kilograms) by a factor of 9.81. The SDS indicates how similar the participant was to the reference population.
Mean Calf Circumference	Baseline, Month 6, Month 12 and Month 18	Calf measurements were taken as a mean of 3 consecutive measurements at largest part of calf muscle, usually about 4 inches down from below the knee.
Mean Height at Months 12 and 18	Month 12 and Month 18	Standing height was taken as a mean of 3 consecutive measurements using a wall mounted stadiometer.
Change From Baseline in Skinfold Thickness-Standard Deviation Score (SDS) at Month 6	Baseline and Month 6	Triceps, supra-iliac and subscapular skinfolds were measured on the right side of the body to the nearest 0.1 mm with a Holtain skinfold caliper. The measurement was performed at the left side of the participant. Triceps skinfold thickness was measured halfway down the left upper arm, while the arm was hanging relaxed at the participant's side. Suprascapular skinfold was measured laterally just below the angle of the left scapula. Suprailiac skinfold was measured just above the iliac crest in the middle-axillary line. SDS indicates how similar the participant was to the reference population.
Mean Height-Standard Deviation Score (SDS) at Months 12 and 18	Month 12 and Month 18	Standing height was taken as a mean of 3 consecutive measurements using a wall mounted stadiometer. The SDS indicates how similar the participant was to the reference population.
Change From Baseline in One-chair Rising Test (Time to Perform the Tasks) at Months 6, 12 and 18	Baseline, Month 6 , Month 12 and Month 18	The Chair rising test is a performance test (total power output) to measure neuromuscular function of complex movement to stand up. Test allows diagnostics of movement deficits using Leonardo jump plate. One stand up test: rising from a chair on the jump plate as quickly as possible with arms crossed over the chest (analysis of time, PJP, PJF and time of fastest rising).
Change From Baseline in Maximal Isometric Grip Force-Standard Deviation Score (MIGF-SDS) at Months 12 and 18	Baseline, Month 12 and Month 18	MIGF was assessed using standard adjustable Jamar dynamometer. MIGF (in Newtons) was calculated by multiplying the dynamometer reading (in kilograms) by a factor of 9.81. The SDS indicates how similar the participant was to the reference population.
Mean Upper Arm Circumference	Baseline, Month 6, Month 12 and Month 18
Change From Baseline in Growth Velocity-Standard Deviation Score (SDS) at Month 6	Baseline and Month 6	Growth velocity measures the annual rate of increase in height. The SDS indicates how similar the participant is to the reference population.
Change From Baseline in Head Circumference-Standard Deviation Score (SDS) at Months 6, 12 and 18	Baseline, Month 6, Month 12 and Month 18	The maximum head circumference (usually horizontal just above the eyebrow ridges), was measured from just above the glabella area to the area near the top of the occipital bone (opisthocranion). The SDS indicates how similar the participant was to the reference population.
Change From Baseline in Height-Standard Deviation Score (SDS) at Months 12 and 18	Baseline, Month 12 and Month 18	Standing height was taken as a mean of 3 consecutive measurements using a wall mounted stadiometer. The SDS indicates how similar the participant was to the reference population.
Change From Baseline in Height-Standard Deviation Score (SDS) at Month 6	Baseline and Month 6	Standing height was taken as a mean of 3 consecutive measurements using a wall mounted stadiometer. The SDS indicates how similar the participant was to the reference population.
Change From Baseline in Growth Velocity-Standard Deviation Score (SDS) at Months 12 and 18	Baseline, Month 12 and Month 18	Growth velocity measures the annual rate of increase in height. The SDS indicates how similar the participant is to the reference population.
Sitting Height-Standard Deviation Score (SDS)	Baseline, Month 6, Month 12 and Month 18	Sitting height was measured using a stadiometer with a specialized chair. The SDS indicates how similar the participant was to the reference population.
Change From Baseline in Head Circumference at Months 6, 12 and 18	Baseline, Month 6, Month 12 and Month 18	The maximum head circumference (usually horizontal just above the eyebrow ridges), was measured from just above the glabella area to the area near the top of the occipital bone (opisthocranion).
Change From Baseline in Skinfold Thickness-Standard Deviation Score (SDS) at Months 12 and 18	Baseline, Month 12 and Month 18	Triceps, supra-iliac and subscapular skinfolds were measured on the right side of the body to the nearest 0.1 mm with a Holtain skinfold caliper. The measurement was performed at the left side of the participant. Triceps skinfold thickness was measured halfway down the left upper arm, while the arm was hanging relaxed at the participant's side. Suprascapular skinfold was measured laterally just below the angle of the left scapula. Suprailiac skinfold was measured just above the iliac crest in the middle-axillary line. SDS indicates how similar the participant was to the reference population.
Body Mass Index-Standard Deviation Score (BMI-SDS)	Baseline, Month 6, Month 12 and Month 18	The BMI was used to measure body fat based on height and weight. It was calculated by body weight (kg) divided by the height (m) squared. The SDS indicates how similar the participant was to the reference population.