Condition category
Pregnancy and Childbirth
Date applied
20/12/2005
Date assigned
20/12/2005
Last edited
14/01/2016
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

Contact information

Type

Scientific

Primary contact

Dr D.C.M. van der Kaay

ORCID ID

Contact details

P/a Dutch Growth Foundation
Westzeedijk 106
Rotterdam
3001 KB
Netherlands
+31 (0)10 225 1533
d.vanderkaay@groeistichting.nl

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

231.731/2003/155; NTR299

Study information

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

Acronym

Dutch SGA study

Study hypothesis

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

Received from the local medical ethics committee

Study design

Multicentre randomised active-controlled parallel-group trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

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

Phase

Not Applicable

Drug names

Genotropin®, Lucrin®

Primary outcome measures

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 trial start date

01/07/2003

Overall trial end date

01/07/2007

Reason abandoned

Eligibility

Participant 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

Participant type

Patient

Age group

Child

Gender

Both

Target number of participants

96

Participant 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

Recruitment start date

01/07/2003

Recruitment end date

01/07/2007

Locations

Countries of recruitment

Netherlands

Trial participating centre

P/a Dutch Growth Foundation
Rotterdam
3001 KB
Netherlands

Sponsor information

Organisation

Dutch Growth Foundation (Netherlands)

Sponsor details

Westzeedijk 106
Rotterdam
3016 AH
Netherlands

Sponsor type

Research organisation

Website

Funders

Funder type

Not defined

Funder name

Not provided at time of registration

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

2009 results in: http://www.ncbi.nlm.nih.gov/pubmed/19158202
2012 results in: http://www.ncbi.nlm.nih.gov/pubmed/22441140
2013 results in: http://www.ncbi.nlm.nih.gov/pubmed/23125290
2015 results in: http://www.ncbi.nlm.nih.gov/pubmed/26259134

Publication citations

  1. Results

    van der Kaay D, Deal C, de Kort S, Willemsen R, Leunissen R, Ester W, Paquette J, van Doorn J, Hokken-Koelega A, Insulin-like growth factor-binding protein-1: serum levels, promoter polymorphism, and associations with components of the metabolic syndrome in short subjects born small for gestational age., J. Clin. Endocrinol. Metab., 2009, 94, 4, 1386-1392, doi: 10.1210/jc.2008-1430.

  2. Results

    Lem AJ, Jobse I, van der Kaay DC, de Ridder MA, Raat H, Hokken-Koelega AC, Health-related quality of life in short children born small for gestational age: effects of growth hormone treatment and postponement of puberty., Horm Res Paediatr, 2012, 77, 3, 170-179, doi: 10.1159/000337218.

  3. Results

    Lem AJ, van der Kaay DC, Hokken-Koelega AC, Bone mineral density and body composition in short children born SGA during growth hormone and gonadotropin releasing hormone analog treatment., J. Clin. Endocrinol. Metab., 2013, 98, 1, 77-86, doi: 10.1210/jc.2012-2492.

  4. Results

    van der Steen M, Lem AJ, van der Kaay DC, Bakker-van Waarde WM, van der Hulst FJ, Neijens FS, Noordam C, Odink RJ, Oostdijk W, Schroor EJ, Westerlaken C, Hokken-Koelega AC, Metabolic Health in Short Children Born Small for Gestational Age Treated With Growth Hormone and Gonadotropin-Releasing Hormone Analog: Results of a Randomized, Dose-Response Trial, J Clin Endocrinol Metab, 2015, 100, 10, 3725-3734, doi: 10.1210/jc.2015-2619.

Additional files

Editorial Notes

14/01/2016: Publication reference added.