Efficacy and safety of long-term growth hormone treatment In short children born small for gestational age above the age of 8 years.|
|- candidate number||1484|
|- NTR Number||NTR299|
|- Date ISRCTN created||20-dec-2005|
|- date ISRCTN requested||18-okt-2005|
|- Date Registered NTR||9-sep-2005|
|- Secondary IDs||231.731/2003/155 |
|- Public Title||Efficacy and safety of long-term growth hormone treatment In short children born small for gestational age above the age of 8 years.|
|- 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|
|- hypothesis||This study aims to evaluate the baseline GH status, body composition and insulin sensitivity in (pre)pubertal short children born 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/m2/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 vs 1 mg GH/m2/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 < 140 cm. |
|- Healt Condition(s) or Problem(s) studied||Small for gestational age (SGA), Children with persistent short stature |
|- Inclusion criteria||1. Children born with a birth length and/or weight < - 2 SD for gestational age (Usher McLean);|
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 < -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 < P50 in prepubertal 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.
|- 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 <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 leukemia;
8. Serious suspicion of psychosocial dwarfism (emotional deprivation).
9. Expected non-compliance.
|- mec approval received||yes|
|- multicenter trial||yes|
|- Type||2 or more arms, randomized|
|- planned startdate ||1-jul-2003|
|- planned closingdate||1-jan-2012|
|- Target number of participants||150|
|- Interventions||All children are treated with Genotropin® (recombinant human somatropine, Pharmacia Corp., Peapack, NJ, USA) 1mg/m2/day until final height. |
During puberty GH therapy 2 versus 1 mg/m2/day will be evaluated.
Children with a height < 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 < 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 ovariae 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.
|- Primary outcome||1. To assess the effect of doubling the GH dose from 1 to26 mg\m2\day versus continuation of treatment with 1 mg GH\m2\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 \m2\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:
a. Insulin sensitivity;
b. Body composition.
|- Secondary outcome||To assess the safety of GH treatment by studying the short- and long-term effects on:|
a. Blood pressure;
b. Thyroid function;
c. Fasting glucose and insulin and HbA1c levels.
|- Trial web site||N/A|
|- status||open: patient inclusion|
|- CONTACT FOR PUBLIC QUERIES||MD. Annemieke J. Lem|
|- CONTACT for SCIENTIFIC QUERIES||MD. Annemieke J. Lem|
|- Sponsor/Initiator ||Dutch Growth Foundation|
(Source(s) of Monetary or Material Support)
|- Publications||Health-Related Quality of Life in Short Children Born Small for Gestational Age: Effects of Growth Hormone Treatment and Postponement of Puberty.|
Lem AJ, Jobse I, van der Kaay DC, de Ridder MA, Raat H, Hokken-Koelega AC.
Horm Res Paediatr. 2012 Mar 21. [Epub ahead of print]
Anti-Mullerian hormone in short girls born small for gestational age and the effect of growth hormone treatment.
Lem AJ, Boonstra VH, Renes JS, Breukhoven PE, de Jong FH, Laven JS, Hokken-Koelega AC.
Hum Reprod. 2011 Apr;26(4):898-903. Epub 2011 Jan 12.
Should short children born small for gestational age with a distance to target height <1 standard deviation score be excluded from growth hormone treatment?
Lem AJ, de Kort SW, de Ridder MA, Hokken-Koelega AC.
Clin Endocrinol (Oxf). 2010 Sep;73(3):355-60. Epub 2010 Jun 9.
Randomized GH trial with two different dosages in combination with a GnRH analogue in short small for gestational age children: effects on metabolic profile and serum GH, IGF1, and IGFBP3 levels.
van der Kaay D, Bakker B, van der Hulst F, Mul D, Mulder J, Schroor E, van Elswijk D, Rowaan I, Willeboer M, de Ridder M, Hokken-Koelega A.
Eur J Endocrinol. 2010 May;162(5):887-95. Epub 2010 Feb 22.
Overnight luteinizing and follicle stimulating hormone profiles during GnRHa treatment in short girls born small for gestational age.
van der Kaay DC, de Jong FH, Laven JS, Hokken-Koelega AC.
J Pediatr Endocrinol Metab. 2009 Feb;22(2):161-9.
Overnight levels of luteinizing hormone, follicle-stimulating hormone and growth hormone before and during gonadotropin-releasing hormone analogue treatment in short boys born small for gestational age.
van der Kaay DC, de Jong FH, Rose SR, Odink RJ, Bakker-van Waarde WM, Sulkers EJ, Hokken-Koelega AC.
Horm Res. 2009;71(5):260-7. Epub 2009 Apr 1.
Reduced levels of GH during GnRH analogue treatment in pubertal short girls born small for gestational age (SGA).
van der Kaay DC, Rose SR, van Dijk M, Noordam C, van Rheenen E, Hokken-Koelega AC.
Clin Endocrinol (Oxf). 2009 Jun;70(6):914-9. Epub 2008 Sep 28.
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.
van der Kaay D, Deal C, de Kort S, Willemsen R, Leunissen R, Ester W, Paquette J, van Doorn J, Hokken-Koelega A.
J Clin Endocrinol Metab. 2009 Apr;94(4):1386-92. Epub 2009 Jan 21.
The effect of growth hormone treatment on metabolic and cardiovascular risk factors is similar in preterm and term short, small for gestational age children.
de Kort SW, Willemsen RH, van der Kaay DC, Hokken-Koelega AC.
Clin Endocrinol (Oxf). 2009 Jul;71(1):65-73. Epub 2008 Dec 15.
Genetic and epigenetic variability in the gene for IGFBP-3 (IGFBP3): correlation with serum IGFBP-3 levels and growth in short children born small for gestational age.
van der Kaay DC, Hendriks AE, Ester WA, Leunissen RW, Willemsen RH, de Kort SW, Paquette JR, Hokken-Koelega AC, Deal CL.
Growth Horm IGF Res. 2009 Jun;19(3):198-205. Epub 2008 Oct 16.
|- Brief summary||This study aims to evaluate the baseline GH status, body composition and insulin sensitivity as such and in relation with each other in pubertal short children born 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/m2/day and the effects on bone maturation, body composition, insulin sensitivity, and other safety parameters.
GH therapy will be continued until attainment of final height.
In addition, this study will evaluate the effect of 2 vs 1 mg GH/m2/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 < 140 cm.
|- Main changes (audit trail)|
|- RECORD||9-sep-2005 - 29-mrt-2012|
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