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

P/a Dutch Growth Foundation
Westzeedijk 106
Rotterdam
3001 KB
Netherlands

Phone +31 (0)10 225 1533
Email d.vanderkaay@groeistichting.nl

Study information

Study designMulticentre randomised active-controlled parallel-group trial
Primary study designInterventional
Secondary study designRandomised controlled trial
Study setting(s)Hospital
Study typeTreatment
Participant information sheet Not available in web format, please use the contact details below to request a patient information sheet
Scientific titleEfficacy and safety of long-term growth hormone treatment In short children born small for gestational age above the age of 8 years
Study acronymDutch SGA study
Study objectivesThis 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) studiedPersistent short stature, small for gestational age (SGA)
InterventionAll 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 typeDrug
Pharmaceutical study type(s)
PhaseNot Applicable
Drug / device / biological / vaccine name(s)Genotropin®, Lucrin®
Primary outcome measure1. 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 measuresTo 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 date01/07/2003
Completion date01/07/2007

Eligibility

Participant type(s)Patient
Age groupChild
SexBoth
Target number of participants96
Total final enrolment107
Key inclusion criteria1. 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 criteria1. 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 enrolment01/07/2003
Date of final enrolment01/07/2007

Locations

Countries of recruitment

  • Netherlands

Study participating centre

P/a Dutch Growth Foundation
Rotterdam
3001 KB
Netherlands

Sponsor information

Dutch Growth Foundation (Netherlands)
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 shareNo
IPD sharing plan summaryNot provided at time of registration
Publication and dissemination planNot 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.