Short Stature
Conditions
Keywords
treatment, growth hormone, childhood, short stature
Brief summary
The objective was to study whether normal growth velocity can be maintained with adapted GH dosage in GH treated prepubertal children who have responded to GH treatment with fulfilled catch up growth (=difference to target height reached, less than - 0.6 SDS).
Detailed description
The aim of the trial is to study the effect of adapted GH treatment in order to find an individualized GH dose maintaining normal growth velocity close to target height SDS and normal metabolism after fulfilled catch up growth in prepubertal children treated with individual doses of GH within the trial 98-0198-003 (1). The overall aim is to find for the individual the lowest effective GH dose during maintenance period, maintaining normal growth velocity and metabolism, i.e. a satisfactory biological active dose.
Interventions
DRUGGenotropin
Children were randomized to either decreased dose by 50% or unchanged dose after 2-3 years of Catch-up growth
Sponsors
Pfizer
Göteborg University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
4 Years to 18 Years
Healthy volunteers
No
Inclusion criteria
* Participated in the 'GH-dose catch-up study' 98- 0198-003. * Midparental height reached (difference less than 0.6 SDS) * Prepubertal at start of the study (girls =B 1, boys: testes :\<; 3ml). * Signed written informed consent from the patient's parents (and the child if old enough)
Exclusion criteria
* Disease affecting growth other than correctly treated hypothyroidism. * Incapable of following the study protocol (i.e. bad compliance in the previous study). * Puberty (\> breast stage 2, or testes \> 4ml). * Poor compliance.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Proportion of Children Maintaining Normal Growth Velocity | twelve months | The proportion of children in the intervention 1 group (=reduced dose) that maintained an individual ΔheightSDS within ±0.3 during the first year of the Maintenance trial, compared to the proportion of children in the intervention 2 group (non-reduced dose) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| IGF-I | start of study to two years after start in the trial | Delta Insulin-like growth factor-I (24 months after start compared to start of study) expressed as ng/ml and converted to standard deviation scores (SDS) to adjust for gender and age. A standard deviation score of 0 is equal to the mean with negative numbers indicating values lower than the mean and positive values higher. A mean value within +-0.5 SDS and a range within +-1.0 SDS is a favorable outcome. |
| Height SDS at Start of Puberty | 1-7 years in the trial | Height at start of puberty measured as cm and expressed as standard deviation score (SDS) to adjust for age and gender |
Other
| Measure | Time frame | Description |
|---|---|---|
| Changes in Height | start of study to two years after start in the trial | Changes in height standard deviation scores (SDS) (calculated as height in cm at start converted to SDS and height in cm after two years in the trial converted to SDS) |
Participant flow
Recruitment details
All children in the fix dose group and children in the individualized dose group who have reached their midparental height SDS (\>- 0.6 SDS) during at least two years of GH-treatment within the 'GH-dose-catch up' study (TR 98-0198-003) and still are prepubertal were eligible in the study.
Pre-assignment details
If glucose levels at the day of inclusion were higher than 7.1 mmol/L, then the child was excluded before assignment.
Participants by arm
| Arm | Count |
|---|---|
| Decreased GH Dose Reduced dose 50% Genotropin
Genotropin: Children were randomized to decreased GH dose by 50% after 2-3 years of Catch-up growth | 27 |
| Unchanged GH Dose Unchanged dose Genotropin
Genotropin: Children were randomized to unchanged GH dose after 2-3 years of Catch-up growth | 38 |
| Control Group Control Group randomized in the previous study to fix dose.
This group of children continued with fix dose in the current trial after signing informed consent. | 33 |
| Total | 98 |
Baseline characteristics
| Characteristic | Control Group | Total | Decreased GH Dose | Unchanged GH Dose |
|---|---|---|---|---|
| Age, Categorical <=18 years | 33 Participants | 98 Participants | 27 Participants | 38 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Continuous | 8.33 years STANDARD_DEVIATION 1.78 | 8.52 years STANDARD_DEVIATION 1.99 | 8.53 years STANDARD_DEVIATION 1.51 | 8.52 years STANDARD_DEVIATION 2.11 |
| Region of Enrollment Sweden | 33 participants | 65 participants | 27 participants | 38 participants |
| Sex: Female, Male Female | 8 Participants | 26 Participants | 7 Participants | 11 Participants |
| Sex: Female, Male Male | 25 Participants | 72 Participants | 20 Participants | 27 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 27 | 0 / 38 | 0 / 33 |
| other Total, other adverse events | 20 / 27 | 25 / 38 | 24 / 33 |
| serious Total, serious adverse events | 3 / 27 | 4 / 38 | 3 / 33 |
Outcome results
Primary
The Proportion of Children Maintaining Normal Growth Velocity
The proportion of children in the intervention 1 group (=reduced dose) that maintained an individual ΔheightSDS within ±0.3 during the first year of the Maintenance trial, compared to the proportion of children in the intervention 2 group (non-reduced dose)
Time frame: twelve months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Decreased GH Dose | The Proportion of Children Maintaining Normal Growth Velocity | 23 Participants |
| Interventional 2 | The Proportion of Children Maintaining Normal Growth Velocity | 32 Participants |
| Control Group | The Proportion of Children Maintaining Normal Growth Velocity | 31 Participants |
Secondary
Height SDS at Start of Puberty
Height at start of puberty measured as cm and expressed as standard deviation score (SDS) to adjust for age and gender
Time frame: 1-7 years in the trial
Population: All 98 Children were measured at start of puberty
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Decreased GH Dose | Height SDS at Start of Puberty | -1.0 standard deviation scores | Standard Deviation 1.02 |
| Interventional 2 | Height SDS at Start of Puberty | -1.06 standard deviation scores | Standard Deviation 0.84 |
| Control Group | Height SDS at Start of Puberty | -0.98 standard deviation scores | Standard Deviation 0.91 |
Secondary
IGF-I
Delta Insulin-like growth factor-I (24 months after start compared to start of study) expressed as ng/ml and converted to standard deviation scores (SDS) to adjust for gender and age. A standard deviation score of 0 is equal to the mean with negative numbers indicating values lower than the mean and positive values higher. A mean value within +-0.5 SDS and a range within +-1.0 SDS is a favorable outcome.
Time frame: start of study to two years after start in the trial
Population: Drop outs due to puberty or adverse events
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Decreased GH Dose | IGF-I | -1.10 standard deviation scores | Standard Deviation 1.14 |
| Interventional 2 | IGF-I | 0.58 standard deviation scores | Standard Deviation 0.91 |
| Control Group | IGF-I | -0.06 standard deviation scores | Standard Deviation 1.26 |
Other Pre-specified
Changes in Height
Changes in height standard deviation scores (SDS) (calculated as height in cm at start converted to SDS and height in cm after two years in the trial converted to SDS)
Time frame: start of study to two years after start in the trial
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Decreased GH Dose | Changes in Height | 0.18 standard deviation scores | Standard Deviation 0.16 |
| Interventional 2 | Changes in Height | 0.57 standard deviation scores | Standard Deviation 0.36 |
| Control Group | Changes in Height | 0.55 standard deviation scores | Standard Deviation 0.26 |