Efficacy and safety of long-term growth hormone treatment In short children born small for gestational age above the age of 8 years.

Recruiting

• Conditions: Children with persistent short stature (<-2.5 SDS) after being born small for gestational age (birth weight and/or birth length <-2 SDS)

• Registration Number: NL-OMON23173
• Lead Sponsor: Dutch Growth FoundationWestzeedijk 1063001 KB Rotterdam

Brief Summary

Health-Related Quality of Life in Short Children Born Small for Gestational Age: Effects of Growth Hormone Treatment and Postponement of Puberty.<br> Lem AJ, Jobse I, van der Kaay DC, de Ridder MA, Raat H, Hokken-Koelega AC.<br> Horm Res Paediatr. 2012 Mar 21. [Epub ahead of print] <br><br> Anti-Mullerian hormone in short girls born small for gestational age and the effect of growth hormone treatment.<br> Lem AJ, Boonstra VH, Renes JS, Breukhoven PE, de Jong FH, Laven JS, Hokken-Koelega AC.<br> Hum Reprod. 2011 Apr;26(4):898-903. Epub 2011 Jan 12. <br><br> Should short children born small for gestational age with a distance to target height <1 standard deviation score be excluded from growth hormone treatment?<br> Lem AJ, de Kort SW, de Ridder MA, Hokken-Koelega AC.<br> Clin Endocrinol (Oxf). 2010 Sep;73(3):355-60. Epub 2010 Jun 9. <br><br> 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.<br> 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.<br> Eur J Endocrinol. 2010 May;162(5):887-95. Epub 2010 Feb 22. <br><br> Overnight luteinizing and follicle stimulating hormone profiles during GnRHa treatment in short girls born small for gestational age.<br> van der Kaay DC, de Jong FH, Laven JS, Hokken-Koelega AC.<br> J Pediatr Endocrinol Metab. 2009 Feb;22(2):161-9. <br><br> 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.<br> van der Kaay DC, de Jong FH, Rose SR, Odink RJ, Bakker-van Waarde WM, Sulkers EJ, Hokken-Koelega AC.<br> Horm Res. 2009;71(5):260-7. Epub 2009 Apr 1. <br><br> Reduced levels of GH during GnRH analogue treatment in pubertal short girls born small for gestational age (SGA).<br> van der Kaay DC, Rose SR, van Dijk M, Noordam C, van Rheenen E, Hokken-Koelega AC.<br> Clin Endocrinol (Oxf). 2009 Jun;70(6):914-9. Epub 2008 Sep 28. <br><br> 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.<br> van der Kaay D, Deal C, de Kort S, Willemsen R, Leunissen R, Ester W, Paquette J, van Doorn J, Hokken-Koelega A.<br> J Clin Endocrinol Metab. 2009 Apr;94(4):1386-92. Epub 2009 Jan 21. <br><br> The effect of growth hormone treatment on metabolic and cardiovascular risk factors is similar in preterm and term short, small for gestational age children.<br> de Kort SW, Willemsen RH, van der Kaay DC, Hokken-Koelega AC.<br> Clin Endocrinol (Oxf). 2009 Jul;71(1):65-73. Epub 2008 Dec 15. <br><br> 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.<br> van der Kaay DC, Hendriks AE, Ester WA, Leunissen RW, Willemsen RH, de Kort SW, Paquette JR, Hokken-Koelega AC, Deal CL.<br> Growth Horm IGF Res. 2009 Jun;19(3):198-205. Epub 2008 Oct 16.

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Last Update Posted: 28 February 2024

Recruitment & Eligibility

• Status: Recruiting
• Sex: Not specified
• Target Recruitment: 150

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;

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;

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
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; <br /><br>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; <bR><br>3. To determine before and during long-term growth hormone treatment:<bR><br>a. Insulin sensitivity; <br /><br>b. Body composition.

Secondary Outcome Measures

Name	Time	Method
To assess the safety of GH treatment by studying the short- and long-term effects on:<br /><br>a. Blood pressure;<br /><br>b. Thyroid function; <br /><br>c. Fasting glucose and insulin and HbA1c levels.<br>