Efficacy and safety of long-term growth hormone treatment In short children born small for gestational age above the age of 8 years
ISRCTN | ISRCTN18062389 |
---|---|
DOI | https://doi.org/10.1186/ISRCTN18062389 |
Secondary identifying numbers | 231.731/2003/155; NTR299 |
- Submission date
- 20/12/2005
- Registration date
- 20/12/2005
- Last edited
- 12/09/2019
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Pregnancy and Childbirth
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Plain English summary of protocol
Not provided at time of registration
Contact information
Dr D.C.M. van der Kaay
Scientific
Scientific
P/a Dutch Growth Foundation
Westzeedijk 106
Rotterdam
3001 KB
Netherlands
Phone | +31 (0)10 225 1533 |
---|---|
d.vanderkaay@groeistichting.nl |
Study information
Study design | Multicentre randomised active-controlled parallel-group trial |
---|---|
Primary study design | Interventional |
Secondary study design | Randomised controlled trial |
Study setting(s) | Hospital |
Study type | Treatment |
Participant information sheet | Not available in web format, please use the contact details below to request a patient information sheet |
Scientific title | Efficacy and safety of long-term growth hormone treatment In short children born small for gestational age above the age of 8 years |
Study acronym | Dutch SGA study |
Study objectives | This study aims to evaluate the baseline growth hormone (GH) status, body composition and insulin sensitivity in (pre-)pubertal short children born small for gestational age (SGA). It also evaluates the effects of GH treatment on GH levels, body composition and insulin sensitivity. Furthermore this study evaluates in a randomised trial pubertal growth during GH therapy 2 versus 1 mg/m^2/day and the effects on bone maturation, body composition, insulin sensitivity, and other safety parameters. In addition, this study will evaluate the effect of 2 versus 1 mg GH/m^2/day on final height in around 50% of the SGA children who will receive treatment with an LHRH analogue for 2 years due to the start of relatively early puberty at a height less than 140 cm. |
Ethics approval(s) | Received from the local medical ethics committee |
Health condition(s) or problem(s) studied | Persistent short stature, small for gestational age (SGA) |
Intervention | All children are treated with Genotropin® (recombinant human somatropine, Pharmacia Corp., Peapack, NJ, USA) 1 mg/m^2/day until final height. During puberty GH therapy 2 versus 1 mg/m^2/day will be evaluated. Children with a height less than 140 cm at the start of puberty will be treated with Lucrin®, an LHRH analogue in a monthly dose depot of 3.75 mg for 2 years. Clinical measurements (height, weight, physical examination) every 3 months until final height (FH). Routine chemistry and haematology at t = 0, 6, 12 months, then 1-yearly until FH. Only in pubertal children with a height less than 140 cm at the start of study: overnight GH profile tests during 12 hours at t = 0, 3 and 12 months. Frequent sampling intravenous glucose tolerance tests (FSIGT) during 2 hours at t = 0 and 12 months. LHRH test (= LHRH or Lucrin test) at t = 0, 3, 6 months. Ultrasound of ovaries and uterus, at t = 0, 6, 12, 24 months. All children dual energy x-ray absorptiometry (DEXA) at t = 0, 6 months, 2 years, then 2-yearly. Bone age determination at t = 0, then yearly until final height. |
Intervention type | Drug |
Pharmaceutical study type(s) | |
Phase | Not Applicable |
Drug / device / biological / vaccine name(s) | Genotropin®, Lucrin® |
Primary outcome measure | 1. To assess the effect of doubling the GH dose from 1 to 26 mg\m^2\day versus continuation of treatment with 1 mg GH\m^2\day on final height, at onset of puberty in short SGA children who start puberty at a height above 140 cm 2. To determine the dose-response effect of 1 versus 2 mg GH\m^2\day in combination with LHRH analogue treatment for 2 years on final height in short SGA children who start puberty at a height below 140 cm 3. To determine before and during long-term growth hormone treatment: insulin sensitivity and body composition |
Secondary outcome measures | To assess the safety of GH treatment by studying the short- and long-term effects on: 1. Blood pressure 2. Thyroid function 3. Fasting glucose and insulin and HbA1c levels |
Overall study start date | 01/07/2003 |
Completion date | 01/07/2007 |
Eligibility
Participant type(s) | Patient |
---|---|
Age group | Child |
Sex | Both |
Target number of participants | 96 |
Total final enrolment | 107 |
Key inclusion criteria | 1. Children born with a birth length and/or weight less than -2 SD for gestational age 2. Short stature defined in prepubertal children as a height SD score below 2.5 according to the Dutch National Growth References of 1997 or a predicted final height less than -2.5 SD score, calculated as the height at start of puberty plus 30 cm for boys and +20 cm for girls 3. Height velocity (cm/year) for chronological age less than P50 in pre-pubertal children 4. Chronological age at start of treatment: 8 years or older (boys and girls) 5. Well documented growth data from birth up to 2 years and at least 1 year before the start of the study 6. Informed consent |
Key exclusion criteria | 1. Turner syndrome in girls, known syndromes and serious dysmorphic symptoms suggestive for a syndrome that has not yet been described, except for Silver Russell Syndrome 2. Severe asphyxia (defined as Apgar score less than 3 after 5 minutes), and no serious diseases such as long-term artificial ventilation and oxygen supply, bronchopulmonary dysplasia or other chronic lung disease 3. Coeliac disease and other chronic or serious diseases of the gastrointestinal tract, heart, genito-urinary tract, liver, lungs, skeleton or central nervous system, or chronic or recurrent major infectious diseases, nutritional and/or vitamin deficiencies 4. Any endocrine or metabolic disorder such as diabetes mellitus, diabetes insipidus, hypothyroidism, or inborn errors of metabolism, except of GHD 5. Medications or interventions during the previous 6 months that might have interfered with growth, such as corticosteroids (including high dose of corticosteroid inhalation), sex steroids, growth hormone, or major surgery (particularly of the spine or extremities) 6. Use of medication that might interfere with growth during GH therapy, such as corticosteroids, sex steroids, LHRH analogue 7. Active or treated malignancy or increased risk of leukaemia 8. Serious suspicion of psychosocial dwarfism (emotional deprivation) 9. Expected non-compliance |
Date of first enrolment | 01/07/2003 |
Date of final enrolment | 01/07/2007 |
Locations
Countries of recruitment
- Netherlands
Study participating centre
P/a Dutch Growth Foundation
Rotterdam
3001 KB
Netherlands
3001 KB
Netherlands
Sponsor information
Dutch Growth Foundation (Netherlands)
Research organisation
Research organisation
Westzeedijk 106
Rotterdam
3016 AH
Netherlands
Funders
Funder type
Not defined
Not provided at time of registration
No information available
Results and Publications
Intention to publish date | |
---|---|
Individual participant data (IPD) Intention to share | No |
IPD sharing plan summary | Not provided at time of registration |
Publication and dissemination plan | Not provided at time of registration |
IPD sharing plan |
Study outputs
Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
---|---|---|---|---|---|
Results article | results | 01/04/2009 | Yes | No | |
Results article | results | 01/04/2012 | Yes | No | |
Results article | results | 01/01/2013 | Yes | No | |
Results article | results | 01/10/2015 | Yes | No | |
Results article | results | 01/11/2018 | 12/09/2019 | Yes | No |
Editorial Notes
12/09/2019: Publication reference and total final enrolment added.
14/01/2016: Publication reference added.