Contact information
Type
Scientific
Primary contact
Dr S.W.K. de Kort
ORCID ID
Contact details
Erasmus Medical Center
Sophia Children's Hospital
Room number sb-2603
P.O. Box 2060
Rotterdam
3000 CB
Netherlands
+31 (0)10 4636363
s.dekort@erasmusmc.nl
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
N/A
Study information
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
Acronym
IUGR-3 study
Study hypothesis
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
Not provided at time of registration
Study design
Randomised, parallel group, multicentre trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Not specified
Trial type
Treatment
Patient information sheet
Condition
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
Phase
Not Specified
Drug names
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 trial start date
01/03/2002
Overall trial end date
01/10/2009
Reason abandoned (if study stopped)
Eligibility
Participant 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
Participant type
Patient
Age group
Child
Gender
Both
Target number of participants
157
Participant 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
Recruitment start date
01/03/2002
Recruitment end date
01/10/2009
Locations
Countries of recruitment
Netherlands
Trial participating centre
Erasmus Medical Center
Rotterdam
3000 CB
Netherlands
Funders
Funder type
Industry
Funder name
Novo Nordisk
Alternative name(s)
Funding Body Type
private sector organisation
Funding Body Subtype
For-profit companies (industry)
Location
Denmark
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
Basic results (scientific)
Publication list
2016 results in https://www.ncbi.nlm.nih.gov/pubmed/28011067