No registrations found.
ID
Source
Brief title
Health condition
1. Small for gestational age (SGA);
2. Intrauterine growth retardation (IUGR).
Sponsors and support
Intervention
Outcome measures
Primary outcome
1. To assess the effect of GH therapy on:
a. linear growth;
b. bone maturation;
c. pubertal development;
d. final height;
in children with IUGR and no catch-up growth.
Secondary outcome
1. To assess the relation between 24-hour plasma GH profiles and the effect of GH therapy with two doses of GH;
2. To assess the additional affects of GH therapy on glucose and lipid metabolism, blood pressure, procollagen-I and III, plasma IGF-I and IGF-binding protein 3 (IGFBP-3);
3. Psychosocial functioning;
4. Intelligence.
Background summary
Multicentred, double-blind, randomized, two-arm trial comparing two dose regimens of Norditropin® (a 2-year initial trial 14/NL and the trial extensions 20/NL (2-years) and 21/NL (till final height). In trial 14/NL, children were randomized to receive GH at either 3 IU (~1mg)/m2/day or 6 IU (~2mg)/m2/day for a 2-year treatment period. The children were stratified by age (3.00-5.99 years; 6.00-8.99 years; 9.00-10.99 years) and by their plasma 24-hour GH profile (normal GH insufficient, unknown).
Subjects who completed this trial continued in the trial extension 20/NL, and continued treatment, without interruption, in double-blind fashion at the dose level at which they were originally randomised.
Eleven older children who did not meet the criteria on age and puberty were included in a separate protocol. These children were treated according to protocol addendum GHRETARD/BPD/16/NL. Trial conduct in 16/NL was the same as that for 14/NL with the exception that all children received GH at 6 IU (~2mg)/m2/day. After two years of treatment, these children were allowed to continue in trial extension 20/NL.
Study objective
GH treatment of short, small-for-gestational-age children has a beneficial effect on linear growth.
Study design
N/A
Intervention
Growth hormone treatment in either 3 or 6 IU (~1 or 2 mg)/m2/day (randomized double-blind dose-response trial).
P.O. Box 2060
A.C.S. Hokken-Koelega
Dr. Molewaterplein 60
Rotterdam 3000 CB
The Netherlands
+31 (0)10 4636744
a.hokken@erasmusmc.nl
P.O. Box 2060
A.C.S. Hokken-Koelega
Dr. Molewaterplein 60
Rotterdam 3000 CB
The Netherlands
+31 (0)10 4636744
a.hokken@erasmusmc.nl
Inclusion criteria
1. Birth length
2. Uncomplicated neonatal period, defined as no signs of:
a. severe asphyxia (Apgar score <3 after 5 minutes);
b. complicated sepsis neonatorum;
c. long-term complicated respiratory ventilation (for instance, bronchopulmonary dysplasia or pneumothorax);
3. No catch-up growth defined as obtaining a height of >= P3 (Roede), within the first two years of life or at a later stage;
4. Height velocity (HV) (cm/year) for chronological age <= P50 (Tanner);
5. Chronological age at start of treatment: girls: 3.00 to 8.99 years; boys: 3.00 to 10.99 years;
6. Prepubertal signs as defined by Tanner stage 1 or testicular volume <4 ml;
7. Well documented growth data from birth up to two years and at least one year before start of treatment;
8. Written informed consent from child and/or parents/guardians.
Exclusion criteria
1. Any endocrine or metabolic disorder (such as diabetes mellitus, diabetes insipidus, hypothyroidism, or inborn errors of metabolism);
2. Disorders of the genito-urinary tract, cardio-pulmonary or gastro-intestinal tract, or nervous system, nutritional and/or vitamin deficiencies;
3. Chromocomal abnormalities or signs of a syndrome, except for Silver-Russel syndrome;
4. Chondrodysplasia;
5. Hydrocephalus;
6. Subjects with active malignant diseases or with increased risk of leukaemia;
7. Serious suspicion of psychosocial dwarfism (emotional deprivation);
8. Previous anabolic sex steroid or GH therapy.
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| NTR-new | NL1008 |
| NTR-old | NTR1037 |
| Other | : |
| ISRCTN | ISRCTN wordt niet meer aangevraagd |
Summary results
2. Sas, T., de Waal, W., Mulder, P., Houdijk, M., Jansen, M., Reeser, M. & Hokken-Koelega, A. (1999) Growth hormone treatment in children with short stature born small for gestational age: 5-year results of a randomized, double-blind, dose-response trial. J Clin Endocrinol Metab, 84, 3064-3070;<br>
3. Sas, T., Mulder, P. & Hokken-Koelega, A. (2000) Body composition, blood pressure, and lipid metabolism before and during long-term growth hormone (GH) treatment in children with short stature born small for gestational age either with or without GH deficiency. J Clin Endocrinol Metab, 85, 3786-3792;<br>
4. Sas, T.C., Gerver, W.J., De Bruin, R., Mulder, P.G., Cole, T.J., De Waal, W. & Hokken-Koelega, A.C. (2000) Body proportions during 6 years of GH treatment in children with short stature born small for gestational age participating in a randomised, double-blind, dose-response trial. Clin Endocrinol (Oxf), 53, 675-681;<br>
5. Sas, T., Mulder, P., Aanstoot, H.J., Houdijk, M., Jansen, M., Reeser, M. & Hokken-Koelega, A. (2001) Carbohydrate metabolism during long-term growth hormone treatment in children with short stature born small for gestational age. Clin Endocrinol (Oxf), 54, 243-251;<br>
6. van Pareren, Y., Mulder, P., Houdijk, M., Jansen, M., Reeser, M. & Hokken-Koelega, A. (2003) Effect of discontinuation of growth hormone treatment on risk factors for cardiovascular disease in adolescents born small for gestational age. J Clin Endocrinol Metab, 88, 347-353;<br>
7. Van Pareren, Y., Mulder, P., Houdijk, M., Jansen, M., Reeser, M. & Hokken-Koelega, A. (2003) Adult height after long-term, continuous growth hormone (GH) treatment in short children born small for gestational age: results of a randomized, double-blind, dose-response GH trial. J Clin Endocrinol Metab, 88, 3584-3590;<br>
8. van Pareren, Y.K., Duivenvoorden, H.J., Slijper, F.S., Koot, H.M. & Hokken-Koelega, A.C. (2004) Intelligence and psychosocial functioning during long-term growth hormone therapy in children born small for gestational age. J Clin Endocrinol Metab, 89, 5295-5302;<br>
9. Bannink, E.M., van Pareren, Y.K., Theunissen, N.C., Raat, H., Mulder, P.G. & Hokken-Koelega, A.C. (2005) Quality of life in adolescents born small for gestational age: does growth hormone make a difference? Horm Res, 64, 166-174;<br>
10. Bannink, E.M., van Doorn, J., Mulder, P.G. & Hokken-Koelega, A.C. (2007) Free/Dissociable Insulin-Like Growth Factor (IGF)-I, Not Total IGF-I, Correlates with Growth Response during Growth Hormone Treatment in Children Born Small for Gestational Age. J Clin Endocrinol Metab, 92, 2992-3000.