Efficacy and safety of growth hormone treatment in short children born small for gestational age; effects of growth hormone levels on growth, insulin sensitivity and body composition
| ISRCTN | ISRCTN65230311 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN65230311 |
| Secondary identifying numbers | N/A |
- Submission date
- 19/07/2006
- Registration date
- 19/07/2006
- Last edited
- 29/12/2016
- 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 S.W.K. de Kort
Scientific
Scientific
Erasmus Medical Center
Sophia Children's Hospital
Room number sb-2603
P.O. Box 2060
Rotterdam
3000 CB
Netherlands
| Phone | +31 (0)10 4636363 |
|---|---|
| s.dekort@erasmusmc.nl |
Study information
| Study design | Randomised, parallel group, multicentre trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Not specified |
| Study type | Treatment |
| Scientific title | Efficacy and safety of growth hormone treatment in short children born small for gestational age; effects of growth hormone levels on growth, insulin sensitivity and body composition |
| Study acronym | IUGR-3 study |
| Study objectives | Children born small for gestational age (SGA) might be at increased risk for developing hypertension, cardiovascular disease and diabetes mellitus type 2. It has been shown that those SGA children with relatively higher growth hormone (GH) levels during an overnight GH-profile had more signs of insulin resistance. GH treatment does not seem to increase the risk of these diseases, but insulin sensitivity has not yet been evaluated in detail and has not yet been studied in relation to age, body composition, and baseline serum levels of GH, insulin-like growth factor (IGF)-1 and IGF-binding proteins. This type of research is very important since it might give clues which children are more prone to developing metabolic syndrome in later life and whether GH treatment during childhood and puberty has any effect on the development of this metabolic syndrome. |
| Ethics approval(s) | Not provided at time of registration |
| Health condition(s) or problem(s) studied | Small for gestational age (SGA), children with persistent short stature |
| Intervention | Growth hormone treatment Norditropin SimpleXx 15 mg/1.5 ml. The first 60 patients of five years and older who are included in the study, will undergo an overnight GH-profile, frequently sampled intravenous glucose tolerance test (FSIGT) and dual energy X-ray absorptiometry (DEXA). After stratification for gender, age, GH status, these patients will be randomised into two different groups: during the first six months, groups A and B will receive GH therapy in a dose of 1 and 2 mg/m^2/day, respectively. Subsequently, all patients will continue GH treatment with a dose of 1 mg/m^2/day. Those patients of five years and older who will not undergo an overnight GH profile, FSIGT and DXA and all patients younger than 5 years will receive 1 mg GH/m2/day. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Not Specified |
| Drug / device / biological / vaccine name(s) | Norditropin |
| Primary outcome measure | 1. To determine before, during and after treatment termination of long-term growth hormone treatment: a. Insulin sensitivity (via frequent sampling intravenous glucose tolerance test) b. Body composition: in relation to each other and baseline serum GH levels during an overnight GH profile and in relation with six months of treatment with two different GH doses 2. To assess the long-term efficacy of biosynthetic GH treatment in a dose of 3 IU/m^2/day on final height and other various auxological parameters |
| Secondary outcome measures | 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, insulin and haemoglobin HbA1c (HbA1c) levels |
| Overall study start date | 01/03/2002 |
| Completion date | 01/10/2009 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Child |
| Sex | Both |
| Target number of participants | 157 |
| Key inclusion criteria | 1. Children born with a birth length and/or weight <2 standard devations (SD) for gestational age (Usher McLean) 2. Neonatal period without signs of severe asphyxia (defined as Apgar score <3 after five minutes), and no serious diseases such as long-term artificial ventilation and oxygen supply, bronchopulmonary dysplasia or other chronic lung diseases 3. Short stature defined as a height SD score below 2.5 according to the Dutch National Growth references of 1997 4. Height velocity (cm/year) for chronological age 5. Chronological age at the start of treatment: 3.00 - 7.99 years (boys and girls) 6. Prepubertal signs defined as 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 the start of the study 8. Both growth hormone deficient and growth hormone insufficient patients 9. Informed consent |
| Key exclusion criteria | 1. Chromosomal disorders, known syndromes and serious dysmorphic symptoms suggestive for a syndrome that has not yet been described, except for Silver Russell syndrome 2. Coeliac disease and other chronic or serious diseases of the gastrointestinal tract, heart, genitourinary tract, liver, lungs, skeleton, central nervous system, metabolic disease, chronic or recurrent major infectious diseases, nutritional and/or vitamin deficiencies 3. Any endocrine or metabolic disorder such as diabetes mellitus, diabetes insipidus, hypothyroidism, or inborn errors of metabolism, except for growth hormone deficiency (GHD) 4. Use of medications or interventions at this moment or during the previous six 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) 5. Active malignancy or increased risk of leukaemia 6. Serious suspicion of psychosocial dwarfism (emotional deprivation) 7. Expected non-compliance |
| Date of first enrolment | 01/03/2002 |
| Date of final enrolment | 01/10/2009 |
Locations
Countries of recruitment
- Netherlands
Study participating centre
Erasmus Medical Center
Rotterdam
3000 CB
Netherlands
3000 CB
Netherlands
Sponsor information
Erasmus Medical Center (The Netherlands)
University/education
University/education
Sophia Children's Hospital
Dr. Molewaterplein 60
Rotterdam
3015 GJ
Netherlands
"ROR" |
https://ror.org/018906e22 |
|---|
Funders
Funder type
Industry
Novo Nordisk
Private sector organisation / For-profit companies (industry)
Private sector organisation / For-profit companies (industry)
- Alternative name(s)
- Novo Nordisk Global
- Location
- Denmark
Results and Publications
| Intention to publish date | |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not provided at time of registration |
| Publication and dissemination plan | Not provided at time of registration |
| IPD sharing plan |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Results article | results | 01/02/2017 | Yes | No |
Editorial Notes
29/12/2016: Publication reference added.
